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392 Cards in this Set
- Front
- Back
What is Sublingual
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ventral surface of the tongue
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What is Buccal
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lining of the cheek
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What are the two general purposes for administering drugs to the oral cavity:
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To achieve systemic or local effects
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In the oral cavity, what is the principle barrier for drug absorption
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Epithelium
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What makes the oral cavity good for systemic delivery
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Highly vascularized
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What does Keratinization help form
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it helps to form a tough barrier
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Are the Buccal and sublingual membranes keratinized
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No
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Which is thicker, buccal or sublingual epithelial layer?
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Buccal > sublingual; buccal epithel is thicker
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Which is more permeable, buccal or sublingual epithelial layer?
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Sublingual > buccal
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What is the pH of Saliva
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about 7
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How is saliva critical for drug delivery?
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it can dissolve the drug but it can also wash it away
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What are the advantages of Sublingual/Buccal Delivery
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1. Avoidance of GI acid degradation, GI enzymatic degradation, and the hepatic first pass effect (drainage is to the jugular vein), 2. Can achieve rapid onset of action and high blood levels (for some drugs), 3. Can also be used for prolonged action (can be several hours for buccal)
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What are the disadvantages of Sublingual/Buccal Delivery
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1. Relatively low permeability for most drugs because of skin like barrier properties (e.g., Small, lipophilic drugs are best absorbed), 2. The drug can be washed away (e.g., by saliva, eating, and drinking), 3. Sometimes unpredictable bioavailability (e.g., due to mucosal variations)
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In dosage form design, Sublingual vs. buccal, which should be designed for rapid release over a short period of time?
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Sublingual products
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Why are sublingual products designed for rapid drug release over a short period of time
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drug dissolve in sublingual pool of saliva, must be quickly absorbed before being washed away
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Why are buccal products generally designed for slower drug release over a sustained period of time?
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has lower permeability; relatively easy to keep dosage forms in place (*but some buccal products work faster (fentanyl))
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Why should buccal/sublingual drugs and excipients should be bland and non-irritating
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so as not to stimulated saliva flow
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What type of sublingual administration is designed to disintegrate rapidly and leave little residue
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Tablets
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Why are compressed tablets usually lightly compressed
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to facilitate disintegration, i.e., Nitroglycerin
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Besides serving as a diluent, what other purpose does lactose have SL NTG tablets
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NTG adsorbed to lactose to reduce explosive risk and help stabilize it
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Are sublingual lyophilized tablets slow or fast dissolving
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Fast-dissolving tablets; Example: Asenapine; peak plasma conc. with in 0.5-1.5 hours (reduced if water is drank within 10 mins)
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How are molded tablets prepared
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Prepared by forcing a moistened blend of drug and excipients into a mold, followed by forcing the wet mass out of the mold and allowing to dry; tend to be softer than compressed tablets. Tablet molds are also available for extemporaneous compounding.
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How should sublingual NTG tablets be stored
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Must be dispensed in the original glass container that is airtight; NTG interacts with and passes though plastic;NTG is volatile thus may evaporate rapidly
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How is sublingual Nitrolingual Spray applied?
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sprayed on or under tongue
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How are sublingual films prepared
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Drug is uniformly mixed with a fast-dissolving polymer (e.g., cellulose-based), plus a plasticizer, flavors, colorants, etc. The technology is also used for some products intended for GI absorption
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Describe buccal chewing gum
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A gum base with several excipients for flavor, texture, stickiness, etc.
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Why is nicotine produced in a chewing gum
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high hepatic first-pass, good buccal absorption
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How is nicotine gum prepared
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Nicotine is bound to a cation exchange resin; nicotine exchanges with saliva (chewing is critical). It's formulated with buffer to raise the pH to 8.5 which increases the nonionized form thus better absorption
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What does the systemic bioavailability of nicotine in gum depend on
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the time the saliva is held in the mouth**if swallowed, nicotine hepatically metabolized
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Describe buccal lozenges
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Hard tablets, typically prepared like hard candy that dissolves slowly in the mouth; e.g., Commit: Similar to Nicorette, the nicotine is bound to a cation exchange resin; cation exchange as the lozenge dissolves
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What are buccal lollipops
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Essentially a lozenge-on-a-stick. e.g., fentanyl citrate lollipop - Actiq (very lipophilic, high hepatic and intestinal first pass) used for pain associated with cancer
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Describe the usage of buccal lollipops
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placed between cheek and gums, then sucked for about 15 mins. Rapid absorption followed by prolonged absorption (rapid from absorption in the mouth, prolonged - from GI absorption)
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Why is the goal of buccal mucoadhesive tablets
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To keep the dosage form in place; Designed to slowly disintegrate/dissolve
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What is an example of mucoadhesive excipients
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cellulose derivatives; Striant (testosterone buccal system)-testosterone (high hepatic 1st pass and lipophilic) stays between cheek and gums until removes (12hrs)
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How are Orally Disintegrating Tablets (for Buccal Drug Delivery) prepared
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Prepared by lyophilization ; e.g. Zelaper (selegiline hydrochlloride)
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How is Zelapar (selegiline hydrochloride) Orally Disintegrating Tablets (for Buccal Drug Delivery) used
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Placed on the tongue where it rapidly dissolves; absorption is buccal, avoid food/liquid 5 minutes before and after
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(2) Fentora (fentanyl citrate) Buccal Tablet (compressed)
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Placed between the cheek and gums where disintegration occurs rapidly; uses Oravescent technology
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Describe oravescent technology
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Oravescent technology involves release of CO2, with pH changes that favor dissolution, then absorption. 1) pH decrease, thus ionized form and dissolution 2) pH then increase favoring unionized form and absorption
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What are some general guidelines for administering buccal or sublingual tablets
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Avoid eating, drinking, chewing, smoking, and talking (if practical) ---do not disturb
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What are the most local common purposes of vaginal dosage forms
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vaginal infection, lubricant, and contraception
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Liquid Dosage form for the vaginal route
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Douche
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Semisolid Dosage forms for the vaginal route
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Creams, gels, ointments, and foams
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Solid Dosage forms for the vaginal route
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Suppositories or compressed tablets shaped like Suppositories
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What are other names for solid vaginal dosage forms
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Other names include pessary, ovule, and insert
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Film Dosage forms for the vaginal route
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similar to oral films, the drug is uniformly dispersed or dissolved in a thin, rapidly disintegrating polymer sheet
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Describe the gross anatomy of the vagina
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The vagina is a fibromuscular tube, about 6 - 10 cm long (adult), extending from the cervix
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Describe the vaginal mucosa
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A mucous membrane composed of a stratified squamous epithelium
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What are the key features of the vaginal mucosa
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Contains rugae and a natural microflora
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What are rugae
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folds in the wall - increase surface area, can help retain the product
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What is the importance of a natural microflora
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important for healthy vaginal mucosa; aerobes and anaerobes
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Describe Vaginal epithelium
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not keratinized; A stratified squamous epithelium composed of 5 strata
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Describe the Mucous layer (vaginal fluid)
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There is a limited amount of vaginal fluid, but it is fairly complex (transudates, exfoliated epithelial cells, leukocytes)
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What is the Source of vaginal secretions
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Vaginal fluid consists mainly of cervical secretions, which flow continuously to the vagina
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How does the vaginal environment maintain an acidic environment that is bacteriostatic
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Lactobacillus acidophilus produces lactic acid from glycogen in the vaginal epithelial cells
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What type of Enzymes are in the vaginal secretions
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peptidases
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Is Venous drainage from the vagina hepatic?
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Venous drainage is not to the hepatic portal system thus no hepatic-first pass
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What three components have significant variations in the vaginal mucosa
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The amount and composition of vaginal fluid, pH, and the epithelium
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How can the amount and composition of vaginal fluid vary
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The amount and consistency varies during the menstrual cycle which can affect drug dissolution and residence time
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Increase in pH between about 4 weeks of age and puberty, and upon menopause means increase risk of what
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infection
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What can be effected by the thickness changes throughout the menstrual cycle
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drug absorption. The epithelium becomes thinner upon menopause
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What is the percentage of systemic absorption Through the Vaginal Epithelium for most current products**often between 1-10%
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often between 1-10%
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Why is there significant interpatient variability for absorption through the vaginal epithelium
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because of variation in vaginal mucosa
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Explain the Possibility of a first uterine pass effect
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There are reports that some intravaginally administered drugs accumulate in uterine tissue which means the uterus could be treated with intervaginal product
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At what pH should products be formulated to match vaginal pH
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keep product pH around 4 to maintain infection resistance; pH is also important for drug solubility and stability
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What are the product attributes after administration
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Retention, liquefaction, distribution
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What characteristics of the product effect the retention so that it is long enough for the drug to distribute adequately
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rheology and level of insertion can be important
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How quickly should the product dissolve or melt
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ideally should be within minutes
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What can happen if the product leaks too quickly or excessively
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can lead to reduced effect and compliance problems
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Explain mucoadhesive (bioadhesive) drugs
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product will stick, wont be as messy, may prolong drug release
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Why are Applicators are usually required for intravaginal delivery
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to help the product to be placed high in the vagina
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How to Use Pessaries or Vaginal Cream
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1. Wash your hands., 2. Remove any foil or plastic covering from the pessary or applicator. 3. If an applicator is supplied, load it with the pessary or cream. 4. Whilst laying down, knees bent and spread apart, gently insert the applicator (or pessary) into the vagina as far as it will comfortably go. 5. Press the plunger to deposit the pessary or cream in the vagina and withdraw the applicator. 6. Wash your hands again.
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What ocular conditions can be treated by topical products
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Glaucoma, Infections, Inflammation, Dry eyes
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The eye wall consists of what three concentric layers:
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Outermost - conjunctiva/sclera and the cornea, Middle - Uveal tract (choroid, ciliary body, and iris), Innermost - retina
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What divides the inside of the eye
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the lens divides the eye into aqueous and vitreous humors (aka anterior and posterial SEGMENTS/REGENS - not chambers)
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What is the aqueous humor divided by
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iris; into anterior and posterior chambers.
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What makes the aqueous humor
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It is continuously generated by the ciliary bodies
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How does the aqueous humor flow
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from the posterior chamber through the pupil
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How does the aqueous humor exit into systemic circulation
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mainly though Schlemms canals
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What are the Surrounding Structures of the eye
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Conjunctiva, Lacrimal Gland, Puncta, Nasolacrimal Apparatus
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Describe the Conjunctiva
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A thin, transparent, vascularized mucous membrane that extends from the edge of the cornea, across a portion of the sclera, then extends to the internal surface of the eyelids to form the conjunctival sacs (cul-de-sacs)
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What is the Lacrimal Gland
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One of the glands responsible for tear production.
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What is one function of tears
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removal of foreign material through the puncta.
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What is the Puncta
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The small openings to the lacrimal canaliculi.
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What is the drainage system for lacrimal fluid
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Nasolacrimal Apparatus
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How do tears drain through the Nasolacrimal Apparatus
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Tears drain through the canaliculi to the lacrimal sac then to the nasal cavity via the lacrimal duct from the nasal cavity they are moved toward the nasopharynx. Tear drainage occurs by gravity and through an active process employing a pumping mechanism. **blinking (15-50x per min)
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What are the 4 mojor Potential Ophthalmic Drug Target Areas
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Pre-ocular structures (e.g., conjunctiva and eyelid (nfections and inflammation)), Cornea (infections and pain), Tissues in the anterior segment, and Tissues in the posterior segment (NOT likely target for topicals)
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What are the Tissues in the anterior segment
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(1) Iris muscles -alpha-1 (2) Ciliary epithelium - alpha-2, beta-2, (3) Ciliary muscle - beta-2
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Im transcorneal Absorption, what are the major pathways for a topical ophthalmic to reach intraocular tissues
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through the cornea and sclera (passage though the cornea dominates)
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What covers the cornea
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Tear film
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What are the three layers of the tear film and what is the function of each layer
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(1) Mucoid layer (Involved in adhesion of the aqueous tear fluid; keeps the cornea wettable), (2) Tear fluid (Aqueous solution of inorganic electrolytes, proteins including enzymes and immunoglobins and glucose), (3) Lipid film; A layer of wax and cholesterol esters adsorbed to the tear fluid. (reduced evaporation of the tear fluid)
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What provides the driving force for passive diffusion through the cornea
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concentration of drug in the tear film (passive diffusion dominates corneal permeation)
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What are the layers of the Cornea
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Epithelium, Stroma, Endothelium
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What are the most important layers for drug absorption
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epithelium, stroma, and endothelium ** lipophilc, hydrophilic, lipophilic
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Describe the Corneal epithelium
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Continuous with the conjunctiva, but with a different thickness, A stratified epithelium, The epithelium is the main barrier for drug passage through the cornea
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What structures increase the surface area or the corneal squamous cells
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surrounded by tight junctions and have microvilli
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What is the main barrier for drug passage through the cornea
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epithelium: It is primarily a lipophilic barrier (lipophilic drugs permeate well); The drug's ionization state can be important (unionized = more lipophilic thus permeated epithelium better)
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What layer of the cornea is a barrier for lipophilic drugs
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Stroma
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Which layer of the cornea provides metabolic exchange between the cornea and the aqueous humor.
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Endothelium
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For Transcorneal Drug Absorption, what kind opf drugs are best absorbed
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Drugs with a moderate octanol/water partition at physiological pH are best absorbed. i.e. because of diverse barriers
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For Transcorneal Drug Absorption, the _________ the tear film, the __________ the penetration
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greater, faster
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What happens to the rate of absorption through damaged epithelium
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increases
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Normally, how much of the dose (instilled as drops) will cross the cornea
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less than 5 %
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What are the possible fates of the drop(s) applied to the eye (before crossing the cornea):
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Spillage, Removal by Nasolacrimal Drainage, Enzymatic degradation
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Once the drug has crossed the cornea, what fates can be met:
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Penetration into deeper intraocular tissues, Binding to proteins, Elimination
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Where are the greatest concentrations are usually achieved
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within the aqueous humor in the anterior region of the eye. The amount reaching the posterior region is usually insignificant
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How can iris color effect the binding to proteins
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some lipophilic drugs can bind to melanin in the iris; in dark irides can reduce the drug effect or act as a depot
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After eye drops are applied, how can the drug be eliminated
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Entry into systemic circulation
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How can the drug can enter the systemic circulation from within the eye:
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via aqueous humor turnover ; exits through the canal of schlenmm or through uveal blood vessels
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Some metabolize drugs and esterases are important for what
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some prodrugs
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What are the routes of systemic absorption
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Absorption through tissues encountered following nasolacrimal drainage; Absorption through blood vessels in the conjunctiva; Absorption from within the eye
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Why does the conjunctiva facilitate drug absorption
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it's more permeable than the cornea and covers a much greater surface area; the conjunctiva is highly vascularized , most that permeates is absorbs systemically
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What is the overall impact of systemic absorption
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over 50% of the instilled dose can be systemically absorbed
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Why is Pseudomonas aeruginosa of great concern
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can invade abraded cornea and cause corneal ulceration and blindness
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What antimicrobial preservatives is most widely used against P. aeruginosa
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Benzalkonium chloride (BAC) (0.01% or less); Can affect corneal penetration.**can act as a penetration enhancer
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What can happen if the concentration of Benzalkonium chloride (BAC) is too high
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Can damage the corneal epithelium
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What is Polyquad (polyquaternium-1)
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antimicrobial preservative; Almost nonsensitizing=alternative to BAC but does not penetrate the cornea well.
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What is Thimerosal (0.001-0.01%)
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An organic mercurial antimicrobial preservative; Hypersensitivity is a problem
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What is the normal pH of tears
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between 7 and 7.4
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Solutions below a pH of 6.6 and above a pH of 9.0 have been associated with what
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irritation, reflex tears, and blinking.**speeds up drop elimination from the eye surface
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What are some important buffers for opthalmics
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acetate, phosphate, citrate, borate; Chosen based on compatibility with the drug product and on desired pH. (often chosen to help stability or stabilize the drug)
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What is used to adjust the pH of opthalmics
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Strong acids (e.g., HCl or H2SO4) and strong bases (e.g., NaOH)
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What is the aproximate Osmolarity (Tonicity) of tears
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about 300 mOsm/kg
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Isotonicity is very important for what
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comfort; Instilled fluids far outside of the normal range can irritate, leading to a reflex tearing and blinking. This will speed up elimination from the eye surface
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What are some common Tonicity modifiers
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NaCl, mannitol, and dextrose
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Increased viscosity can do what
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Increase retention time / reduce the drainage rate (Can increase bioavailablilty); can irritate if too high
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What are some Viscosity modifiers
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glycerin, cellulose derivatives (e.g. hydroxyethylcellulose), polyvinyl alcohol, PEGs
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Why are viscosity modifiers used
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Increase viscosity can increase retention/reduce drainage time and they must have a lubricating effect
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What type of doseage form are Liquid Ophthalmics (Eyedrops)
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Solutions or suspensions
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How is the formulation and manufacturing of a solution done
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Dissolve drug and part or all of excipients. Sterilize by heat or membrane filtration. If required, add the other sterilized excipients, bring to volume with sterile water.
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How is the formulation and manufacturing of a suspension done
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Reduce the particle size to less than 10 micrometersl; smaller particles reduce irritation and speeds dissolution. Can't filter-sterilize , so must aseptically add the sterilized solid to the sterilized solution.
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What types of drugs are suspension eye drop s used for
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Used for poorly water-soluble drugs or to improve stability. They do not provide a drug depot, but they do mix with tears less rapidly thus remain in the cul-de-sac longer
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What is an example of an antioxidant
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Sodium metabisulfites
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What is an example of a chelator
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EDTA disodium
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Besides its ability to limit oxidation by chelating metals, what other important function does EDTA have
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increase the activity of BAC against P aeruginosa
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What are some examples of Surfactants
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Polysorbate (Tween) 80 and tyloxapol
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How are surfactants used in eye drops
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Used as wetting agents for suspensions and can facilitate spreading of the drops because they reduce surface tension
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How are eye drops packaged
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In a sterile Drop-tainer
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What is the main advantage of a semisolid Ophthalmic/Ointment
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Prolonged contact time
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What is the main disadvantage of a semisolid Ophthalmic/Ointment
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Can cause blurred vision
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How is the formulation and manufacturing of a opthalminc ointment done
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The ointment base is usually white petrolatum, with or without mineral oil to reduce viscosity. Sterilize the ointment base by heat, then filter while molten. Add sterilized drug and excipients aseptically.
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What is used in preparing ophthalmic Gels
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These employ a gel former such as Carbomer or gums (e.g., cellulose derivatives)
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After using eye drops, why do you apply gentle pressure against the inner corner of the eye
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(nasolacrimal occlusion) to slow drainage as well as limit systemic effects
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What does the dissolution test measure
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measures the rate and extent of the drug in the tablet to go into solution
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When is the dissolution test a particularly important test for drugs with limited water solubility
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where dissolution is the rate-limiting step for absorption
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Describe the rotating basket method (USP)
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The tablet is placed inside a stainless steel wire basket, which is rotated at a fixed speed while immersed in a dissolution medium (at body temperature) contained in a cylindrical vessel.
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Describe the paddle method (USP)
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Allow the dosage to sink to the bottom of the vessel. Agitate the dissolution medium. Dissolution medium is specified
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In dissolution tests, how humch of the drug should be disolved in 45 minutes
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75%
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What is an example of dissolution medium for basic drugs
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0.1N HCl; Protonation/dissolution in stomach
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What is an example of dissolution medium for acidic drugs
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Buffer at pH of 7; Deprotonation/dissolution area in small intestine
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What is an example of dissolution medium for neutral drugs
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Water
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In order to maintain dissolution, how should tablets be stored
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store tablets under proper conditions so they maintain the ability to dissolve (tightly sealed, away from high humidity and high temperatures)
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How does the lumen increase the risk of esophageal adhesions
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It is narrow and coated with mucus; there is little water
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What can result following Esophageal Adhesion
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following adhesion, the drug will dissolve, possible irritation, inflammation and ulceration; e.g., aspirin, NSAIDs, tetracycline, ferrous sulfate, KCl
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What factors cause a predisposition to adhesions
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shape (flat vs round), size, surface properties (sticky if wet), patient position (e.g. supine position increases the risk), volume of water (if none, increase risk), and disease
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What is the recommended method for taking tablets to avoid adhesions
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take the tablet while standing with a glass full of water at least 1 hour before bed
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Describe the tablet form: Lozenges
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prepared and formulated like hard candy
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Describe the tablet form: Troches
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compressed into a hard disc
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Describe the tablet form: Chewable tablets
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Prepared by wet granulation, sometimes without a disintegrant (chewing takes place of disintegrant). Often have a high mannitol or xylitol content and flavorants to give cooling sensation in the mouth
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How are Lozenges and Troches administered
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Intended to dissolve slowly (e.g., 30 minutes) in the mouth, usually for a local effect.(eg for thrush)
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How are Chewable tablets administered
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Pleasant tasting tablets designed to disintegrate smoothly in the mouth; Examples: vitamins, antacids, antibiotics
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Describe the tablet form: Effervescent tablets
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Prepared by compressing the drug with effervescent salt mixtures (e.g., sodium bicarbonate and citric acid)
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How are Effervescent tablets administered
|
Generally designed to be dissolved in liquid prior to ingestion;effervescent KCl tablets
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How are Fast-dissolving tablets administered
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Designed to disintegrate rapidly in the mouth before swallowing; less than 1 min
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What are some claims for fast-dissolving tablets
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Easier to take and swallow (typically you don’t need water (though following with water may be recommended)). Possible faster onset of action , but often not true (faster because of disintegration before swallowing; BUT drug dissolution can be rate limiting, drug particles might be coated)
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What methods of formulation and manufacture (in the U.S.) are used to prepare fast-dissolving tablets
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Lyophilization (freeze-drying) - Leaves a very porous product (sponge like, tablet usually brittle thus special packaging and handling). Direct compression with special disintegrants (ex:superdisintegrants - very hydrophilic cellulose deriv and effervescent disintegrants; these tablets must be well protected)
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How are suppositories used
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for insertion into the rectum, vagina or the urethra
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What happens after suppositories are inserted
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after insertion, suppositories soften, melt or dissolve in the cavity fluids (due to body temp)
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What are the weights of rectal, vaginal, and urethral suppositories
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rectal-2 g, vaginal-5 g, urethral-2 g female, 4 g male
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What uses are suppositories are indicated for
|
administering drugs to infants and small children, severely debilitated patients, those who cannot take medications orally; for either systemic or local application
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What are the advantages of suppositories over oral therapy
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Avoid loss of the drug (Acidic pH of stomach or enzymes destroy drug), drugs can irritate stomach, and some drugs can be destroyed by first liver passage
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What are the disadvantages of Suppository
|
un-comfortable, Variation of absorption (physiological), Irritation for mucous caused by some drugs or bases
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Describe the anorectal physiology
|
~10” long (20-30 cm), Nonmotile, 2-3 ml inert mucous fluid, No villi/microvilli, has blood and lymphatic vessels, and pH: 7 to 8
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What are some treatment uses of suppositories
|
Hemorrhoid (astringent, local anesthetic, vasoconstrictor, antipruritic, antiseptic); Fungal infection; Bacterial infection; Chronic inflammation; Constipation (Glycerin S.)
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After Rectal Insertion, how much of the drug is absorbed into blood circulation?
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50-70%
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What is the anorectal Main Blood Circulation
|
1. Inferior haemorrhoidal vein (HV), 2. Middle HV, 3. Superior (upper) HV.
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What types of drugs can be used in suppositories
|
anti-emetic, tranquilizer, vasodilator, analgesic, hypnotic, antipyretic, antiasthmatic
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What Physicochemical Factors Affect Rectal Absorption
|
Lipid solubility (melt and release from base), Particle size (dissolution rate, absorption-diffuse), Suppository vehicle
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The ideal suppository base should:
|
be nontoxic, nonirritating, and easily formed by compression or molding; dissolve or disintegrate in the presence of mucous secretions (pH 7-8); melt at body temperature to allow for the release of the medication; be stable on storage, not bind or otherwise interfere with release and absorption of drug substances.
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How are suppository bases classified?
|
according to their composition and physical properties
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What are the types of suppository bases (according to their composition and physical properties)
|
Oleaginous (fatty) bases, Water soluble or miscible bases
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Why are pharmaceutical additives added to suppositories
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To Improve Quality
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What are some common pharmaceutical additives added to suppositories
|
plasticizer - Cetylalcohol, Propylene glycol antioxidant, dispersant – Surfactant, Absorbance enhancer
|
|
What are used as a Oil-Soluble suppository bases
|
Theobroma Oil or cocoa butter and Synthetic Triglycerides
|
|
Describe the triglycerides of Cocoa Butter
|
All the acids are bonded to glycerin, forming an important number of triglycerides. Of these acids, 80% are disaturated triglycerides, of which 20% are of the SOS type, 55% POS, and the remaining 5% are POP (Stearic Acid, Palmitic Acid, Oleic Acid)
|
|
What gives Cocoa Butter its physical and chemical behavior, mainly in its fusion and solidification properties
|
Its triglyceride composition (mixture of liquid triglycerides entrapped in a network of crystalline, solid triglycerides)
|
|
What happens if cocoa butter is heated above 35°C (95°F)?
|
it melts to a bland, nonirritating oil.
|
|
What happens to Cocoa butter if it's overheated?
|
Cocoa butter is a polymorphic compound and if overheated will convert to a metastable structure that melts in the 25° to 30°C (77° to 86°F) range.
|
|
What are the 4 forms of cocoa butter crystals
|
1. beta crystal (mp 34-36 °C) -what you want, 2. beta’ crystal* (mp 27 °C), 3. alpha crystal* (mp 22 °C), 4. gamma crystal* (mp 18 °C) (liquid)
|
|
Describe Synthetic Triglycerides used are suppository bases
|
Consists of hydrogenated vegetable oil, Do not exhibit polymorphism, More expansive
|
|
What is an example of a synthetic triglycerides used as suppository base
|
Fattybase: triglycerides derived from palm, palm kernel and coconut oils, stable with a low irritation profile, needs no special storage conditions, exhibits excellent mold release characteristics, solid with a melting point of 35-37°C
|
|
What are used as Water Soluble/Water Miscible suppository bases
|
Glycerinated Gelatin and Polyethylene Glycol (PEG) polymers
|
|
What are Glycerinated Gelatin suppositories composed of
|
70% glycerin, 20% gelatin and 10% water [translucent]
|
|
How should Glycerinated Gelatin suppositories be packaged
|
in tight containers, as they are hygroscopic
|
|
What isn't Glycerinated Gelatin recommended as a rectal suppository base
|
may exert an osmotic effect and a defecation reflex; useful suppository base, particularly for vaginal suppositories
|
|
Describe the physical state in terms of polymers for Polyethylene Glycol (PEG) polymers
|
<1000=liquid >1000=solid
|
|
Describe Polyethylene Glycol (PEG) polymers for use as a suppository base
|
are chemically stable, miscible with water and mucous secretions, can be formulated, either by molding or compression
|
|
What aren't Polyethylene Glycol (PEG) polymers stored in polystyrene prescription vials
|
the polyethylene glycol will adversely interact with polystyrene (use glass containers)
|
|
What is the major disadvantage of Polyethylene Glycol (PEG) polymers
|
incompatibility with a large number of drugs; e.g. silver tannins, aspirin, quinine, indomethacin; Sodium barbital, salicylic acid, camphor will crystallize out of PEG suppositories
|
|
What three methods can be used to prepare suppositories
|
Rolled (Hand-Shaped) Suppositories– Only possible with cocoa butter base; Compression-Molded (Fused) Suppositories– no heat, mold under pressure; Fusion or Melt Molding (most common)
|
|
Explain why density calculations and mold calibrations are required to provide accurate doses of suppositories
|
measured by weight but compounded by volume: Suppositories are generally made from solid ingredients and drugs which are measured by weight. When they are mixed, melted, and poured into suppository mold cavities, they occupy a volume –the volume of the mold cavity.
|
|
What is the Archimedes Principle
|
The weight of the displaced fluid can be found mathematically: Density = mass / volume
|
|
How do you determine the amount of base required in compounding suppositories
|
Density Factor = weight of drug / weight of base displaced: When a drug is placed in a suppository base, it will displace an amount of base as a function of its density. The density factor is used to determine how much of a base will be displaced by a drug.
|
|
How are suppositories compounded when the density factor is not known
|
Density Factor is experimentally determined by the double casting technique. Double melt technique used (heat exposure)
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|
Why using the topical route
|
Hydration, Protection, Systemic effect (transdermal drug delivery), Local effects = drug action
|
|
What are the Skins functions
|
Protective barrier on body surface to physical, chemical and biological intrusions, Homeostasis (temperature & water), Sensory, Secretory (vitamin D production), Excretory (via sweat glands)
|
|
What are the epidermis' 5 sublayers of keratinocytes (strata)
|
Stratum Corneum, Stratum Lucidum, Stratum Granulosum, Stratum Spinosum, Stratum Basale/Germinativum
|
|
How thick is the epidermis
|
Thickness varies: 75-150 μm in thin skin; 400-600 μm in thick skin
|
|
What are the mechanical functions of the epidermis
|
Provides mechanical protection, Prevents fluid loss, Keeps microorganisms from invading the body
|
|
Are there vessels in the epidermis
|
No vessels in epidermis
|
|
Describe the Stratum Corneum
|
Horned layer: Dead cells, 15‐20 layers in thick skin, 3‐4 layers in thin skin, Flattened non‐nucleated cells filled with keratin filaments (these cells can also absorb water), surface cells constantly sloughed off
|
|
Where is the Stratum Corneum found
|
This layer is only found on the soles of the feet and the palms of the hands; More common in thick skin
|
|
Describe the Stratum Lucidum
|
Thin, translucent lightly stained layer of non‐nucleated cells; Different arrangement of filaments
|
|
Describe the Stratum Granulosum
|
3‐5 layers of polygonal cells with central nuclei and many basophilic granules; Keratohyalin granules contain proteins that bind keratin filaments together; Membrane coating granules also present; secrete to extracellular matrix to make it more waterproof
|
|
What is the is the highest layer in the epidermis where living cells are found
|
Stratum Granulosum
|
|
Describe the Stratum Spinosum
|
Multilayer arrangement of cuboidal, polygonal or squamous cells, extensions with desmosomes, link proteins that attach the cell surface adhesion proteins to intracellular keratin cytoskeletal filaments
|
|
What are cytokeratins
|
Intermediate filaments which are composed of keratin. Synthesized in the Stratum Spinosum
|
|
Describe the Stratum Basale/Germinativum
|
layer of keratinocytes that lies at the base of the epidermis immediately above the dermis. It consists of a single layer of tall, simple columnar epithelial cells lying on a basement membrane. These cells undergo rapid cell division, mitosis
|
|
What are some Epidermal characteristics
|
Cells accumulate keratin and eventually are shed (continuously renewing, 0.06 0.1 mm thick), Epidermal ridges are interlocked with dermal papillae (Fingerprints, Improve gripping ability)
|
|
What are Langerhans cells for and what layer of the epidermis are they found
|
Fro immunity in s. spinosum
|
|
What are Merkel cells for and what layer of the epidermis are they found
|
For sensitivity in s. germinativum
|
|
What gives skin its color
|
melanin amount, carotene content in subcutaneous fat and vascularization
|
|
What produces Melanin and where is it produced
|
by melanocytes in stratum basale; melanin forms from tyrosine
|
|
What is melanin
|
Melanin is any of the oxyacetylene, polyaniline, and polypyrrole blacks and browns or their mixed copolymers.
|
|
What do Epidermal cells synthesize when exposed to UV
|
vitamin D3 (cholecalciferol)
|
|
What does epidermal growth factor effect
|
Growth, Division, Repair, Secretion
|
|
The dermis is structurally divided into what two areas
|
a superficial area adjacent to the epidermis, called the papillary region and a deep thicker area known as the reticular region.
|
|
describe the papillary region of the dermis
|
composed of loose connective tissue; named for its fingerlike projections called papillae, that extend toward the epidermis. The papillae provide the dermis with a bumpy surface that interdigitates with the epidermis, strengthening the connection between the two layers of skin.
|
|
What are the features of the dermis
|
Network of elastic fibers (elasticity decreases with age), Many blood and lymph vessels, Papillary layer vessels supply epidermis, Arteriovenous shunts for blood pressure and temperature regulation, all epidermal structures (hair follicles, sweat and sebaceous glands) penetrate into the dermis, Many sensory nerves in skin (touch, pain, temperature sensation), Sympathetic vasoconstrictor fibers, piloerector fibers and sudomotor fibers
|
|
What is the Hypodermis (Subcutaneous layer)
|
Adipose connective tissue. The hypodermis is not part of the skin, and lies below the dermis.
|
|
What is the purpose of the hypodermis
|
Loose connective tissue attaches skin to subjacent organs and tissues; this loose flexible attachment is so skin can slide over organs (the hypodermis contains 50% of body fat). Fat serves as padding and insulation for the body.
|
|
What are the Skin Appendages (accessories)
|
sweat & sebaceous glands, hair follicles & hairs, nails, nerves & nervous receptors
|
|
Topical dosage forms generally contain the following ingredients:
|
Base or body of the dosage form, Medicinal agent (not always the case), Preservative (espicially if water is added)
|
|
Ointments are used topically for several purposes:
|
Protectants, Antiseptics, Emollients (soften), Antipruritics (for dry/itchy), Kerotolytics (soften by loosening), Astringents (to shrink tissues)
|
|
What types of ointments are there
|
medicated or nonmedicated
|
|
Ointments are defined as what
|
are semisolid preparations intended for external uses
|
|
Describe Non-medicated ointments
|
emollient or lubricant , vehicle for the preparation of medicated ointments
|
|
Why is the vehicle or base of an ointment is of prime importance
|
In the case of a protective ointment, it serves to protect the skin against moisture, air, sun rays and other external factors.
|
|
What are the 5 types of ointment bases
|
Hydrocarbon bases, Absorption bases, Emulsion bases water‐in‐oil type, Emulsion bases oil‐in‐water type, Water‐miscible bases
|
|
In general, how are ointment bases classified
|
classified according to their interaction with water
|
|
Synonym of Hydrocarbon bases is?
|
Oleaginous Bases
|
|
Characteristics of hydrocarbon bases
|
Will not absorb water, Not water washable, Insoluble in water, Emollient, Occlusive, Greasy
|
|
Describe Occlusive bases
|
applied to the skin and stays on the skin; a film so water won't evaporate. It will soften the skin and loosen the skin tissues.
|
|
What are 4 examples of hydrocarbon bases
|
Petrolatum, White petrolatum, Yellow ointment, Yellow wax
|
|
Describe Petrolatum
|
purified mixture of semisolid hydrocarbons, melting point 38‐68 oC, yellow to light amber, commercial product: Vaseline)
|
|
Describe White petrolatum
|
Bleached petrolatum; not water washable, commercial product: white vaseline)
|
|
Describe Yellow ointment
|
95 % petrolatum + 5 % yellow wax, synonym: simple ointment
|
|
Where is Yellow wax obtained from
|
obtained from honeycomb of the bee
|
|
Describe how Petroleum jelly or petrolatum is made
|
Petroleum jelly or petrolatum is a byproduct of the refining of petroleum, made from the residue of petroleum distillation left in the still after all the oil has been vaporized.
|
|
What are the Important properties of hydrocarbon bases
|
Therapeutic and Patient Acceptance
|
|
What are Therapeutic Advantages of topical delivery
|
Upon application to the skin, a hydrocarbon base will form an adherent, continuous, greasy, water repellant film; Good occlusiveness: This can have an emollient effect (hydrates skin) and can enhance drug permeation; Prolonged contact with the skin; Good protection
|
|
What are the twp types of Absorption bases
|
1. Permit the incorporation of aqueous solutions; Form W/O emulsions ; Single phase e.g. Hydrophilic petrolatum 2. Are W/O emulsions; Two phase system e.g. Lanolin
|
|
What are the general characteristics of absorption bases
|
Insoluble in water, Not water washable, Anhydrous, Can absorb water, Emollient, Occlusive, Greasy
|
|
Describe absorption properties of Anhydrous absorption bases
|
Contain agents that confer an ability to absorb water. They can also absorb alcohol, but to a lesser degree.
|
|
What are two Examples of W/O emulsions
|
Hydrophilic petrolatum, USP, Aquaphor - petrolatum, mineral oil, mineral wax, woolwax alcohol
|
|
Describe the absorption properties of W/O absorption bases
|
Similar to anhydrous absorption bases, except that these already contain varying amounts of water.
|
|
What are two examples of W/O absorption bases Examples
|
Lanolin, USP, Cold Cream
|
|
Where is Lanolin obtained from
|
Obtained from sheep wool, purified
|
|
How much water can lanolin absorb
|
Can absorb up to 30% of water
|
|
What are Emulsion Bases, O/W Type
|
Water removable ointment bases
|
|
What are the Characteristics of emulsion bases, O/W types:
|
Insoluble in water, Water washable, Will absorb water, Contains water, Emollient, Non ‐ Occlusive, Non ‐ Greasy
|
|
What is an Example of emulsion bases, O/W types
|
Hydrophilic ointment
|
|
What is the purpose of stearyl alcohol and white petrolatum in emulsion bases
|
oily phase
|
|
What is the purpose of water and propylene glycol in emulsion bases
|
aqueous phase
|
|
What is the purpose of sodium laurylsulfate
|
emulsifying agent
|
|
What are the characteristics of Water-Soluble Bases
|
Water soluble, Water washable, Will absorb water, Non - Occlusive, Non - Greasy
|
|
What are some Examples of water-soluble bases
|
Polyethylene glycol (PEG) ointment, Glyceryl Monostearate, Cellulose derivatives, carbopol 934
|
|
Explain the density of different Polyethylene glycol (PEG) ointments
|
Polyethylene Glycol 3350 (solid) High#; Polyethylene Glycol 400 (liquid) Low #
|
|
What is Carbopol used for
|
Thickening agent
|
|
What are the criteria for the Selection of Appropriate Base type
|
Desired release rate, Desirability topical or percutaneous drug absorption, Desirability of occlusion, Stability of drug in vehicle, Influence of drug on consistency or other features of ointment base, Patient factor ‐ dry or weeping (oozing) skin
|
|
Define Water Number
|
Ability of an ointment base to incorporate water without loosing its consistency.
|
|
What is the Water Number equivalent
|
the number of grams of water that can be incorporated into 100 grams of the base.
|
|
What is the water number of hydrocarbon bases
|
0 to 5
|
|
What is the water number of Absorption bases
|
100 to 800
|
|
What are the two methods of Preparation of Ointments
|
Incorporation and fusion
|
|
Describe the incorporation process of preparing ointments
|
" mix together (mortar & pestle, spatula & slab – levigating the powder mechanical incorporation, reduction of particle size in suspending agent compatible with the ointment base)
|
|
Describe the fusion method of preparing ointments
|
components of an ointment melted together and cooled with constant stirring until congealed
|
|
About how much ointment Is lost in the compounding process
|
Between 2 and 4 grams of an ointment may be lost in the compounding process.
|
|
How much excess of ointment should be prepared to compensate for loss
|
General rule: add 10% excess to the prescribed amount.
|
|
What must be considered when choosing Levigating Agents
|
Must be compatible with base – External phase of 2-phase systems, Mustn’t unduly influence product viscosity -Mineral oil & glycerin (Main agents), - Propylene glycol PEG 400, cottonseed oil, caster oil, Surfactants , e.g. polysorbate 80 (Tween 80), Chose Powders over crystalline drugs - less gritty
|
|
What are Post Failure Fixes when preparing ointments
|
Very difficult to fix once you have problems, Keep triturating; Start over
|
|
In fusion, what is Incorporated into the ointment
|
Wax & hard fusible bodies into soft oleaginous materials
|
|
In Preparation of ointments, how do you avoid excess heat
|
Melt on water bath
|
|
How do you add ingredients to an ointment
|
In order of decreasing melting points, Heat to fusion point, Add liquid ingredients. Mix phases by stirring to homogeneous preparation, Powder added after base congeals
|
|
When to Use the fusion process ?
|
For Solids that cant’ be easily triturated: Beeswax, Cetyl alcohol, Paraffin, Stearic acid, Any fusible solid
|
|
What can happen if you over heat a ointments during compounding
|
Lanolin, oleic acid, fatty acids, etc. can oxidize; may be discolored. Heat labile components can degrade (Methylparaben & Propylparaben, drugs)
|
|
In fusion what are the Post Failure Fixes for phase separation
|
i.e. cold mixed, reheat heat and stir vigorously
|
|
In fusion what are the Post Failure Fixes for low viscosity
|
add more high η / melting point ingredients; e.g. Beeswax, paraffin, stearic acid
|
|
In fusion what are the Post Failure Fixes for poor dispersion
|
reheat & add more surfactant; lanolin, etc.
|
|
At what temperature will most ingredients used in ointment bases liquefy
|
around 70°C.
|
|
What is helpful in order to mix oil and aqueous phases together :
|
heat the aqueous phase a few degrees higher than the oil phase prior to mixing. The aqueous phase tends to cool faster than the oil phase and may cause premature solidification of some ingredients.
|
|
In mixing aqueous and oil phases, why do you use the lowest temperature possible and keep the time of heating as short as possible.
|
This will minimize the quantity of water lost through evaporation.
|
|
What ingredients of ointments should be melted first
|
Melt the ingredient with the highest melting point first. Reduce the heat to melt the ingredient with the next lowest melting point. Continue this process until all ingredients have been added. This will ensure that the ingredients were exposed to the lowest possible temperature and thus enhance the stability of the final product.
|
|
What happens if you rush the cooling of ointments
|
Change the consistency of the final product! I.e. makes it more stiff
|
|
When are volatile ingredients such as oils, flavors, or drugs, added to the topical drug
|
when the product is cool to the back of the hand. or it will evaporate
|
|
How are ointments filled into jars
|
fill from the bottom while turning the jar; stab the ointment from time to time to release air pockets
|
|
How are ointments filled into tubes
|
Roll the glassine paper into a tube and insert into the tube, with the cap off, press down on the bottom and pull the paper from the tube OR use a Ziploc bag with a urethra tip and inject the ointment into the tube
|
|
What is the Quality Control for ointments
|
Check the final product for the following characteristics
|
|
What are the quality control parameters for ointments
|
Final product weight, Visual appearance, Color, Odor, Viscosity, Homogeneity/phase separation
|
|
What are some Chemical antimicrobial preservatives
|
phydroxybenzoates, phenols, benzoic acid, sorbic acid, quaternary ammonium salts, organic mercury compounds, formaldehyde
|
|
What is the purpose of Absorption Enhancers
|
Facilitate the absorption of drugs through the skin; Changing the solvent properties of the stratum corneum
|
|
What are some examples of absorption enhancers
|
dimethylsulfoxide, urea, citric acids
|
|
Why are Co-Solvents added to ointments
|
In addition to helping to solubilize drugs, they can help keep drugs in solution after application of the dosage form.
|
|
What are some examples of co-solvents used in ointements
|
glycerin, propylene glycol, ethanol Propylene glycol: used in O/W creams to prevent precipitation of the drug as the cream dries to a thin film.
|
|
Compare the hydrocarbon bases of creams and ointments
|
creams less than 50% hydrocarbon bases, ointments more than 50 % hydrocarbon bases
|
|
Describe creams
|
opaque solids, or thick liquids intended for external application, Are emulsions (O/W), Usually the internal phase ranges from 15 - 40% w/w. They can absorb varying amounts of water. Under optimal conditions, the drug concentrates without crystallizing out.
|
|
Describe “Vanishing Creams”
|
O/W emulsion: After application: water evaporates, leaving a thin residue film of stearic acid
|
|
What are Important therapeutic properties of o/w creams
|
The high concentration in the drug film can be good for drug delivery. The thin film is not continuous and not oleaginous, so it will be less occlusive than oily ointments. Since they are less occlusive, o/w creams will generally be less protective and less emollient than the oily ointments. Most acceptable topical dosage form!
|
|
Describe Pastes
|
Intended for application to the skin, Applied to area that requires protection, Contain a larger proportion of solid material than ointments, Stiffer than ointments; high concentration of powders
|
|
What is the definition of powders
|
dry, finely divided drugs and / or chemicals intended for internal or external use (dusting powders)
|
|
What Therapeutic properties do powder have
|
They can promote drying (absorb liquids); They can reduce friction
|
|
What are some Examples of powders and their therapeutic properties
|
Talc is more lubricating, but doesn't absorb water; Corn starch is less lubricating, but absorbs water; Zinc oxide falls in between
|
|
What is a gel?
|
Are semisolid systems. The movement of the dispersing medium is restricted by an interlacing 3D-network of particles
|
|
What causes the viscosity of a gel
|
Viscosity is caused by the interlacing
|
|
What are the applications of gels
|
Oral, Topical, Intranasal, Vaginal, Rectal
|
|
Two-phase system (e.g. Aluminum hydroxide) of a gel is defined as:
|
If the gel mass consists of a network of small inorganic discrete particles:
|
|
Single-phase system (e.g. Carbomer) of a gel is defined as:
|
If the gel mass consists of a network of large organic particles
|
|
What are the three types of Hydrogen gels
|
"Inorganic (Silica, bentonite,
aluminum); Natural and synthetic gums (Pectin, sodium alginate); Organic (Methylcellulose)" |
|
What are the three types of Organogels
|
Hydrocabon type (Mineral oil, PEG); Soap base (Aluminum stearate); Hydrophillic organogles (Carbowax bases)
|
|
What are the Characteristics of Gels
|
Can be clear or turbid, To appeal to the consumer, gels should have clarity and sparkle, Most gels are water washable, greaseless
|
|
Why use a gel?
|
Gels are useful as liquid formulations in oral, topical, intranasally, vaginal, and rectal administration. They have a cooling effect and they can moisturize
|
|
What are the Disadvantage of a Gel
|
bacterial / mold growth due to high content of water
|
|
Define Imbibition
|
Soaking up liquid without a marked increase in volume
|
|
Define Swelling
|
Soaking up liquid with an increase in volume
|
|
Define Syneresis
|
Gel exudes fluid - causing shrinkage; Elastic contraction of the polymer
|
|
Define Thixotropy
|
viscous during storage but loses consistency and become fluid upon shaking. (i.e. ketchup)
|
|
Define Xerogel
|
Liquid is removed from a gel, only the framework remains
|
|
Where is Alginic Acid obtained from
|
Obtained from seaweed
|
|
What are the characteristics of Alginic Acid
|
Tasteless, odorless. Swells in water ~ 200 – 300 times its own weight
|
|
What is the most common Alginic Acid
|
Most common alginate: calcium alginate gel
|
|
What industry is Alginic Acid used it
|
Used in food industry (ice cream, yoghurt)
|
|
What are Carbomers (Carbopol)
|
acrylic acid based polymers
|
|
What does the viscosity of Carbomer (Carbopol) depend on
|
gel viscosity is pH dependent
|
|
Describe the form of Carbomer (Carbopol) at low and high pHs
|
form acidic aqueous solutions (pH ~ 3), thicken at a higher pH (5-6) (NaOH, KOH)
|
|
What is the maximum electrolytes that can be added to Carbomer (Carbopol) before a rubbery mass forms
|
3%
|
|
What happens when alcohol is added to Carbomer (Carbopol)
|
Addition of alcohol: viscosity decreases
|
|
What is Carbomer (Carbopol) used in
|
Used for: oral suspensions, topical gels
|
|
What are some examples of cellulose derivatives
|
Methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose (CMC)
|
|
Describe the viscosity characteristics of cellulose derivatives
|
Viscosity of all derivatives is maintained over a wide pH range (3-11), except CMC
|
|
What are cellulose derivatives compatible with
|
Compatible with water and alcohol
|
|
Esxplain the stability of Carboxymethyl Cellulose CMC
|
Soluble in water at all temperatures; Sensitive to pH, viscosity < pH5; Stable between pH 7-9
|
|
How is Carboxymethyl Cellulose CMC used in food
|
very broad usage; salad dressings, ice cream
|
|
Describe the structure of Gum Arabic (Acacia senegal)
|
Highly branched with b-Galactose backbone
|
|
What are the physiochemical properties of Gum Arabic (Acacia senegal)
|
Water soluble, fat insoluble; Low viscosity gum; Viscosity affected by pH and salts
|
|
What are the Food uses of Gum Arabic (Acacia senegal)
|
Stabilizer for flavor emulsions; Encapsulated flavors; Water binding; Inhibit sugar crystallization
|
|
Where is Gum Tragacanth (Astragalus gummifer) derived from
|
sap of several species of Middle Eastern legumes
|
|
Describe the Polymer of Gum Tragacanth
|
Polymer of Galacturonic Acid + Galactose + Galactose + Arabinose + xylose; Viscosity (varies with grade) 600 - 4,000 CPS at 1%; Acid stable at pH 4-8
|
|
Where is Gelatine derived from
|
Gelatin is a protein produced by partial hydrolysis of collagen extracted from the bones and connective tissues of animals
|
|
Describe the viscosity characteristics of gelatine
|
Forms a solution of high viscosity in hot water, which sets to a gel on cooling
|
|
What is Plastibase
|
Mixture of 5% low-molecular weight polyethylene and 95% mineral oil.
|
|
Describe the characteristics of Plastibase
|
Mineral oil is immobilized by in the network of entangled insoluble polyethylene chains. Gel can be heated up to 60°C (140°F) without substantial loss of viscosity.
|
|
What is the trade name of Poloxamers
|
Pluronics
|
|
Explain the thermoreversible gels of Poloxamers
|
liquids at cool, gels at room or body temperature.
|
|
Describe the polymer structure of poloxamers
|
nonionic block copolymers: central hydrophobic chain of polyoxypropylene (poly-propylene oxide) flanked by two hydrophilic chains of polyoxyethylene (poly-ethylene oxide)
|
|
What is Bentonite
|
hydrated aluminum silicate
|
|
Where is Bentonite derived from
|
Bentonite usually forms from eathering of volcanic ash, most often in the presence of water.
|
|
What kind of gel is Bentonite
|
thixotropic gel, swells approx. 12 times its volume
|
|
How is Bentonite prepared
|
preparation of 5% bentonite in water
|
|
GEL COMPOSITION typically consists of what components
|
Gelling agent, Water, Cosolvents, Preservatives, Stabilizers
|
|
What alters the consistency of a gel
|
tangling
|
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What happens if the gelling agent is added to the dispersing medium
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agent tends to “clump”
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How do you fix clumping gelling agent
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sieve the agent onto the surface of the medium as medium is stirring
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What gels are recommended for oral use
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Only Carbopol® 934P, methylcellulose, hydroxypropylmethylcellulose and CMC
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When should the drug be added to a gel during preparation
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Drug should be added before the gel is formed. Drug should not interfere with gel formation
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What temps are Poloxamers, methylcellulose most soluble
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COLD water
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What temps are gelatine most soluble
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HOT
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What temps are carbomers, alginic acid most soluble
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TEMPID
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How are gels PACKGAGED/STORED/LABELED
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Tight containers (tubes, jars, squeeze bottles), Room or Refrigerated Temperatures, as appropriate, Prior to use….store in tight containers.
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Why using the topical route
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Hydration, Protection, Systemic effect (transdermal drug delivery), Local effects = drug action
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What are the Skins functions
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Protective barrier on body surface to physical, chemical and biological intrusions, Homeostasis (temperature & water), Sensory, Secretory (vitamin D production), Excretory (via sweat glands)
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What are the epidermis' 5 sublayers of keratinocytes (strata)
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Stratum Corneum, Stratum Lucidum, Stratum Granulosum, Stratum Spinosum, Stratum Basale/Germinativum
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How thick is the epidermis
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Thickness varies: 75-150 μm in thin skin; 400-600 μm in thick skin
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What are the mechanical functions of the epidermis
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Provides mechanical protection, Prevents fluid loss, Keeps microorganisms from invading the body
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Are there vessels in the epidermis
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No vessels in epidermis
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Describe the Stratum Corneum
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Horned layer: Dead cells, 15‐20 layers in thick skin, 3‐4 layers in thin skin, Flattened non‐nucleated cells filled with keratin filaments (these cells can also absorb water), surface cells constantly sloughed off
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Where is the Stratum Corneum found
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This layer is only found on the soles of the feet and the palms of the hands; More common in thick skin
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Describe the Stratum Lucidum
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Thin, translucent lightly stained layer of non‐nucleated cells; Different arrangement of filaments
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Describe the Stratum Granulosum
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3‐5 layers of polygonal cells with central nuclei and many basophilic granules; Keratohyalin granules contain proteins that bind keratin filaments together; Membrane coating granules also present; secrete to extracellular matrix to make it more waterproof
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What is the is the highest layer in the epidermis where living cells are found
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Stratum Granulosum
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Describe the Stratum Spinosum
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Multilayer arrangement of cuboidal, polygonal or squamous cells, extensions with desmosomes, link proteins that attach the cell surface adhesion proteins to intracellular keratin cytoskeletal filaments
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What are cytokeratins
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Intermediate filaments which are composed of keratin. Synthesized in the Stratum Spinosum
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Describe the Stratum Basale/Germinativum
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layer of keratinocytes that lies at the base of the epidermis immediately above the dermis. It consists of a single layer of tall, simple columnar epithelial cells lying on a basement membrane. These cells undergo rapid cell division, mitosis
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What are some Epidermal characteristics
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Cells accumulate keratin and eventually are shed (continuously renewing, 0.06 0.1 mm thick), Epidermal ridges are interlocked with dermal papillae (Fingerprints, Improve gripping ability)
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What are Langerhans cells for and what layer of the epidermis are they found
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Fro immunity in s. spinosum
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What are Merkel cells for and what layer of the epidermis are they found
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For sensitivity in s. germinativum
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What gives skin its color
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melanin amount, carotene content in subcutaneous fat and vascularization
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What produces Melanin and where is it produced
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by melanocytes in stratum basale; melanin forms from tyrosine
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What is melanin
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Melanin is any of the oxyacetylene, polyaniline, and polypyrrole blacks and browns or their mixed copolymers.
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What do Epidermal cells synthesize when exposed to UV
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vitamin D3 (cholecalciferol)
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What does epidermal growth factor effect
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Growth, Division, Repair, Secretion
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The dermis is structurally divided into what two areas
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a superficial area adjacent to the epidermis, called the papillary region and a deep thicker area known as the reticular region.
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describe the papillary region of the dermis
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composed of loose connective tissue; named for its fingerlike projections called papillae, that extend toward the epidermis. The papillae provide the dermis with a bumpy surface that interdigitates with the epidermis, strengthening the connection between the two layers of skin.
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What are the features of the dermis
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Network of elastic fibers (elasticity decreases with age), Many blood and lymph vessels, Papillary layer vessels supply epidermis, Arteriovenous shunts for blood pressure and temperature regulation, all epidermal structures (hair follicles, sweat and sebaceous glands) penetrate into the dermis, Many sensory nerves in skin (touch, pain, temperature sensation), Sympathetic vasoconstrictor fibers, piloerector fibers and sudomotor fibers
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