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165 Cards in this Set
- Front
- Back
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Basic Gelatin Formulation Includes what 3 ingredients?
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Gelatin
Sugar Water Can absorbe up to 10x its weight |
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Advantages of hard gel capsules (HGC)?
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-rapid dissolution
-flexibility in formulation -taste/odor masking -protection against light and oxygen -good patient compliance -different sizes |
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Disadvantages of hard gel capsules (HC)?
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-slow manufacture than tablets
-cost -hygroscopic -rapid release of highly soluble salts -adhesion to esophagus -not suitibale for strict vegetarians |
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Largest size of capsule to smallest size of capsule
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Large- 000
Small-5 |
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Pulvule vs Spansule
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Pulvule- tapered at one end
Spansule- tapered at both ends Conventional- no tapering |
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Can capsules be filled with all of the following?
Dry Powders Semisolids Liquids |
Yes.
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Name the type of capsules used in double blind clinical trials
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DBcaps
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Materials not suitable for Capsule formulation?
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aqueous-based liquids
deliquescent materials hygroscopic materials |
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Name some absorbants that may help minimize chemical incompatibilities in capsules
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Magnesiumcarbonate and Kaolin
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What is the name of the improved capsule that is suited for moisture sensitive formulas, non-animal capsule, and meets cultural and dietary needs?
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HPMC Capsules
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What are Pullulan Capsules?
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100% natural
made of water soluble vegetable derived polysaccaride produced by fermentation odorless, tasteless, and biodegradable impermeabel to oxygen transmission starch, preservative and glutten free non-GMO |
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What are Licaps (capsugel)?
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Leak proofed capsules with gelatin band around capsule joint
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What makes a substance a candidate for liquid filling in capsules?
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enhanced bioavailability
stability high potency low melting point sustained release materials |
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Describe the Novel Capsule Delivery System
PulsinCap |
water insolbue body
water soluble cap drug formulation is behind hydrogel plug which is ejected when swollen, drug is then released small intestine or colon |
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Press Fit verse Xpress-Fit Capsule
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Press fit- gelcaps meet at midpoint
Xpress-fit- leave gap inbetween gelcaps |
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What are some applications of soft gel capsules (SGC)?
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swallow whole
chewable lozenges delayed release suppository Tamper evident |
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Composition of soft gel capsules (SGC)
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gelatin
plasticizers (glycerin, propylene glycol, sorbitol) Preservatives colorant Residual moisture 6-10% |
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Requirements of fill material for SGC
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pH 2.5-7.5
low conc of water <5% Drug is not soluble inwater use of ethanol as cosolvent no aldehydes and aqueous emulsions |
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These are examples of what?
vitamin E chloral hydrate procardia Capsules OTC cough/cold/allergy products |
SGC
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Hard vs Soft Gelatin Capsules
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short disintegration of SGC
in house manufacturing (lower costs) absense of hygroscopic plasticizers less drug migration into shell multiple fills |
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Are Topicals used for local, systemic, or both?
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Both
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Dermatological vs Transdermal
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Dermatological- skin is target organ
Transdermal- delivery of drug through the skin to another organ |
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Permeation of drug through the laminate of barriers occurs by what type of diffusion?
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Passive
Intercellular Transappendageal Transcullular |
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colloidal system that is a mixture of two immiscible liquids
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Emulsion
stabalized by use of emulsifier/surfactant- prevents emulsion seperation |
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O/W vs W/O emulsions
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O/W- oil is the dispersed phase
W/O- water is the dispersed phase |
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What are some permeation enhncers for emulsions?
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alcohol
oils esters |
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Different bases used for Ointment
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Hydrocarbon- waterfree (petrolium)
Water-removable- oil in water emulsions may be diluted with water Water-soluble bases- all water soluble components, softens with addition of water (PEG) Absorption Bases 1. w/o emulsions that permit the incorporation of small additional quantities of aqueous solutions 2. incorporation of aqueous solutions (not easily removed from skin) |
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Two ways to prepare ointments
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Incorporation- mixed together
Fusion- metled together and cooled |
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Chemical anti-microbial preservatives used to inhibit growth of contaminating microorganisms in Topicals
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Benzoid Acid
Sorbic Acid p-hydroxy Benzoates |
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Primary vs Secondary packaging
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Primary- tubes, cans, jars, sticks, pouches
secondary- pouches, insertes, leaflets, bar codes, labelling |
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Microbial and analutical evalution of ointment mandatory by what law
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21 CFR Sec 211
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Creams vs Ointments
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less viscous than oitments
no greasy feel on skin if oil in water easier to spread and remove from skin |
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Lotions are usually what?
O/W or W/O |
O/W
with low to medium viscosity may contain one or more active ingredients |
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emulsions vs micro emulsions
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emulsion: 1-20 micrometers (usually droplets)
micro: 10-200 nanometers |
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Typical preservative for ophthalmic gels
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Benzalkonium chloride
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outer layer of skin
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epidermis
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protective layer of skin containing dead cells and a lipid matrix
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stratum corneum
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lower part of the skin that contains blood vessels
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dermis
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excipients that enhance the penetration of drug molecules in to and through the skin
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penetration enhancer
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product applide directly to the skin is called what?
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Topical Delivery
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shortened form of surface active agent; chemical that stabilized mixures of oil and water by reducing the surface tension at the interface between the oil and water molecules
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surfactant
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high viscous or semisolid substance used on the skin as a comsmetic, emollient, or medicament
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ointment
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semisolid emulsion applied to the skin
low to medium vsicosity emulsion applied to the skin |
Cream
Lotion |
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semisolid system rich in liquid for external application to the skin
ointment with a high solid content |
Gel
Paste |
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what is it called to grind to a fine smooth powder while in moist condition
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Lavigation
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What is the mucociliary clearance mechanism?
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mucous layer is propelled backward into GIT by microvilli and cilia
mucous renewed every 15-20 minutes |
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Examplesof Local Nasal Drug Delivery?
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Beconase AQ nasal spray- allergies
Afrin nasal spray- congestion Ocean Mist saline |
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Examples of Systemic Nasal Drug Delivery?
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Amyl Nitrate- anginal pain
Miacalcin (Calcitonin)- osteoporosis Imetrix and Zomig spray- migraines FluMist- active immunization |
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Bioadhesives used to increase residence time for nasal absorption
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Chitosan
Starch HPMC |
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Penetration enhancers used to loosen the tight junctions between epithelial cells in the nasal cavitiy
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azone, ethanol (extraction of lipid bilayers)
DMSO, Azone (fluidization of lipid bilayer) Azone, DMSO (enhancing drug partitioning |
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Colloid carriers used to improve Nasal drug absorption
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Liposomes
Micro and Nanoparticles |
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Requirements for Nasal Formulations
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Isotonic to nasal fluid (0.9% NaCl)
Buffered to maintain pH 5.5-6.5 should not be used longer than 3-5 days (cause rebound effect) |
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What type of cells found on the floor of the mouth where SL tablets are absorbed?
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non-keratinized, thin, multi-layers of epithelial cells
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what was the first SL product?
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Nitroglycerine in 1879
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exipients used in dissolving tablets
exipients in disintegrating tablets? |
Mannitol
Crospovidone, L-HPC, soidium starch glycolate |
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Mucoadhesives are required for which delivery form?
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Buccal Drug Delivery
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Examples of Buccal products?
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Fentora (fentanyl buccal tablet)
Cephalon Onsolis (film-strip) Actiq (lollipop) |
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Topical vs Transdermal
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Topical- local action
Transdermal- systemic drug delivery |
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First Transdermal Patch
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Scop Patch in 1979
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Name the transdermal patch that is used for:
motion sickness angina hypertension postmenopause smoking cessation |
Name the transdermal patch that is used for:
motion sickness- SCOPOLAMINE angina- NITROGLYCERIN hypertension- CLONIDINE postmenopause- ESTRADIOL smoking cessation- NICOTINE |
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outermost desquamating 'horny' layer of skin
what is special about it? |
stratum corneum
rate limiting barrier to percutaneous drug transport described as hydrophilic protein 'bricks' in a lipophilic mortar b/c 40% lipids 40% protein 20% water |
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What are teh macro-routes of drug penetration through skin?
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sweat duct
SC Hair Follicle |
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Active Technique for drug absorption
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Ionophoresis- electronic current
Sonophoresis- ultrasound |
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do corns and warts increase or decrease absorption?
do inflammation and psoriasis increase or decrease absorption? |
Decrease
Increase |
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Is there a dramatic difference in skin absorption of young compared to elderly?
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No
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What are rubefacients?
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agent that increases peripheral blood flow to increase skin absorption by raising the concentration gradient across the skin
ex: Alcohol |
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How do Vasocontricting agents affect absorption of topical/ transdermal drugs?
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reduces absorption
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Where is post-auricular skin?
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behind the ears
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give an example of a drug that is metabolized by the skin
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Prednisolone
pro-drug that enters systemic circulation after absorption through skin |
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what is the ideal pH for the skin to absorb drugs?
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pH 3-9
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What is the ideal partition coefficient for percutaneous drug absorption?
high low medium |
high- will be absorbed but stay in skin
low- will not be absorbed *medium*- will be absorbed and are soluble drug should have adequate solubility in water and oil |
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for good topical absorption, drug should be smaller than what?
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<500 Daltons
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What are the ideal limits for the physiochemical properties of drug candidates for passive transdermal delivery?
Aqueous Solubility Lipophilicity Molecular Weight Melting Point pH Dose Deliverable what is the only drug that meets all of these properties? |
What are the ideal limits for the physiochemical properties of drug candidates for passive transdermal delivery?
Aqueous Solubility >1mg/ml Lipophilicity 10<K o/w <1000 Molecular Weight < 500 Da Melting Point <200 C pH 5-9 Dose Deliverable <10mg/day Nicotine |
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What is Fick's Law?
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Rate of drug transport across the skin
proportional to oil/water partition coefficient, concentration, surface area inversely proportional to the thicknes of SC |
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Name 2 methods of increasing skin absorption
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1. Hydration
2. Prodrugs |
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Name 2 hydrophilic polymers used in trandermal gel formations to increase drug absorption
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HPMC
HPC |
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Name some Penetration Enhancers for increasing skin absorption
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water
Dimethylsulpoxide Fatty Acids Azone Surfactants Urea Alcohols Glycols essential oils terpenes |
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name enhancers that interact with intercellular lipid structure of SC as to disrupt it and increase permeation
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Ethanol
menthol carvone limonene (terpnes) |
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solvents that can enter SC and change its solvent properties and thus increase the partitioning of drug into horny layer (Partitioning promotion)
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ethanol
propylene glycol |
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What are 4 components of Transdermal Therapeutic System?
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1. Drug
2. Backing Film 3. Adhesive 4. Release liner |
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What are the three designs of TTS?
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1. Matrix type
2. adhesive controlled 3. Membrane controlled |
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Describe the Membrane-controlled TTS
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5 layers
Backing Drug Rate contolling membrane* skin adhesive Protective Film (Less stable than other forms) |
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Describe the Matrix Type TTS
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three layers
backing layer drug matrix adhesive protective film (No release liner) thinner and has more stability compared to membrane-controlled TTS |
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Describe the Adhesive Controlled TTS
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two layers
drug is dispersed or dissolved in adhesive adhesive layer is covered with backing membrane and protective strippable film SC regulates rate of drug release, not the TTS |
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Transdermal patch used to treat motion sickness; it is membrane-controlled TTS, also control side effects of anticancer drugs and inhibits radiation sickness
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Scopolamine
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TTS used for treatment of angina and congestive heart failure
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Nitroglycerine
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TTS used for treating menopausal symptoms
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Estradiol
oral estrogen therapy damages liver or increases rick of hypertension |
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TTS used for treating hypertension; also used to treat symptoms associated with stopping smoking; common to have skin irritation
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clonidine
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TTS used to treat chronic intractable pain such as that produced by cancer
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Fentanyl
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TTS used to treat hypogonadism
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Testosterone Patch
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What are Depilatory agents?
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agents capable of removing hair
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Can the TTS patches by left on when showering, bathing, or swimming?
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Yes
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How does Ultrasound increase skin absorption?
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disturbs the lipid packing in intercellular spaces of SC by HEATING AND CAVITATION EFFECTS and thus enhances skin absorption
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What is electroporation?
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method of increasing skin absorption by creating aqueous pores in lipid bilayers by the application of short electrical pulses of 100-1000 V/cm
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What is Tape Stripping?
What is Laser Ablation? |
a way to remove horny layer prior to drug application
adhesive tape is applied afer shaving the skin and then removed so as to remove SC Laser Ablation is similair concept, but instead of tape it uses high powered pulses from a laser |
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What is the active method of increasing skin absorption that involves solid silicon needles (coated with drug) or hollow metal needles (filled with drug) that penetrate horny layer without breaking nor stimulating nerves in deeper tissue?
feels like cat's tongue |
Microneedles
400 micro-needles insert the drug |
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What is the PowderJet system?
What is the Intraject System? |
needle free injection using supersonic shockwave of helium gas to propel particles through SC into lower layers
Intraject- vaccine gun designed to deliver liquids through skin without the use of needles |
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Name the three regions of the lungs
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1. Nasopharyngeal (upper)
2. Tracheo-bronchial (central) 3. Alveolar |
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Three principle mechanisms by which particles are deposited in the lungs?
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1. Inertial impaction (particles with diameter > 5 micrometers)
2. Sedimentation 3. Diffusion |
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_________ deposition is a velocity dependent phenomenon
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Inertial deposition
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__________ deposition occurs where the air stream velocity is relatively low
mainly in small airways and lung periphery |
Deposition
Particles 0.5-3 micrometers |
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_________ deposition produces Brownian motion in the respiratory tract; occurs in small airways and lung periphery
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Deposition by Diffusion
size < 0.5 micrometers |
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volume of gas inhaled and exhaled during one respiratory cycle
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Tidal Volume
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Name three types of aerosol generator/device used in pulmonary drug delivery
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1. Metered dose inhaler (MDI)- delivers a fixed volume
2. Dry powder inhaler (DPI) 3. Nebulizer |
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Types of Spacer Devices
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1. Simple tube extension
2. Valved holding chamber 3. Reverse flow device |
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Name the MDI products for:
anti-inflammatory Antivirals Bronchodilators Antiallergics Mucolytics Antibiotics |
Name the MDI products for:
anti-inflammatory- Beclomethasone Antivirals-Ribavirin Bronchodilators- Albuterol and Ipratropium Antiallergics- Cromolyn sodium Mucolytics- N-acetyl cysteine Antibiotics-Tobramycin and Gentamycin |
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What is the maximum dose for MDI?
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5 mg
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pulmonary drug delivery devices containing solid drug suspended in a dry powder mix that can be fluidized when patients inhale
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Dry Powder inhaler (DPI)
breath activated, no propellants |
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What is the agent in DPIs that is usually used to improve handling, dispensing, and metering of the drug?
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Lactose
Mannitol and glucose can also be used |
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DPI that do not use any exipients
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Pulmicort Turbuhaler (bedesonide)
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Examples of DPI products
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Diskhaler-Relenza
Diskus- Fluticasone Aerolizer- Formoterol fumarate Flexhaler- Budesonide Handihaler-Tiotropium Rotahaler-Terbutaline Exubera-Inhaled insulin |
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drug delivery device that can convert aqueous solutions or micronized suspensions of drug into an aerosol for inhalations
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Nebulizers
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Two types of Nebulizers
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1. Air-jet: compressed air mixes with solution to form aerosol
2. Ultrasonic nebulizer: ultrasonic energy generate aerosol, less viable than air-jet |
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Why was Exubera recalled?
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(inhaled insulin)
caused lung damage |
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How much fluid can an eye accommodate if no blinking?
How much fluid can an eye accomodate with blinking? |
30 microliters
10 microliters |
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A single ophthalmic drop contains how much liquid?
What is the optimal volume to be administered? |
50 microliters
5-10 microliters (eye can only accomodate 30 microliters) |
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Retention time of ophthalmic solution is long or short?
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Short
(1-2 min) bioavailability can be less than 1% |
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What are the 3 parts of the cornea?
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epithelium
stroma endothelium |
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What type of drugs are absorbed through the cornea?
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unionized and drugs with both water and lipid solubility
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What enzyme is abundantly available in corneal epithelium?
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choline esterase
breaks down lipophilic esterified prodrugs |
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The following ophthalmic prodrug are metabolized into what metabolite in the eye?
Dipivalyl Levobunolol |
Dipivalyl-> Epinephrine
Levobunolol-> Dihydroevobunolol |
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What is the prefered method of sterilizing ophthalmic solutions?
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Autoclaving (121 C for 15 min)
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Name some preservatives in ophthalmic drugs?
Which preservative cannot be autoclaved? |
Benzalkonium chloride
Benzethonium Chloride Chlorbutanol (NO AUTOCLAVE) Phenylmercuric acetate Phenylmercuric nitrate Thimerosal |
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What are ophthalmic preservatives not effective against?
|
Pseuduomoas aeruginosa
may cause ulceration or blindness Mixtures of preservatives are effective: Benzalkonium Cl with Polymyxin B sulfate or disodium EDTA |
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Name two methods for adjustment of isotonicity of ophthalmic solutions
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1. Freezing-point method
2. Sodium Chloride equivalent method |
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What is the pH of tears?
|
pH 7.4
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Name Viscosity enhancing/thickening agents for ophthalmic solutions
optimal viscosity range? |
methylcellulose (also used as tear replacement)
hydroxypropyl methylcellulose (HPMC) polyvinyl alcohol Optimal range for final viscosity= 15-25 cp |
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What should be done when using ophthalmic drops to prevent drainage and enhance corneal contact time of the drug?
|
press inner corner of eye by the nose to compress the nasolachrymal duct
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What are OCUSERTS?
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insoluble ophthalmic insert that releases drug at a constant and reproducible rate for a prolonged period of time
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What is Lacrisert (Merck)?
|
rod-shaped water-soluble form of hydroxypropy cllulose (HPC)
placed in the inferior of cul-de-sac of the eye once or twice daily for the treatment of dry eye |
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What is Retisert?
|
first intravitreal drug implant for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye
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What is one of the leading causes of blindness for middle-aged people in the Western world?
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Uveitis
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What is Vitrasert?
|
implant that delivers ganciclovir intraocularly in paitents with AIDs-related Cytomegalovirus (CMV)
slowly releases drug over a 5-8 month period surgically place in the posterior segment of the eye |
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Difference between packaging of otic and ophthalmic solutions
|
otic- glas or plastic containers with dropper
ophthalmic- usually plastic container with dropper |
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What is efffect do these Otic solutions have?
Akericaine Cerumenex Chloromycetin Otobiotic |
What is efffect do these Otic solutions have?
Akericaine- local anesthetic Cerumenex- removes impacted ear wax Chloromycetin- anti-infective Otobiotic- superficial bacterial infections |
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Perservative agents used in otic solutions?
|
chlorobutanol
thimerosal combos of methyl and propyl parabens |
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Do otic preparations need to by pyrogen-free?
|
NO
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Ways to sterilize otic preparations?
|
1. Autoclaving
2. ionizing radiation |
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Are otic preparations considered to be topical?
|
YES
|
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What products are used to soften impacted cerumen?
|
mineral oil
vegetable oil hydrogen peroxide |
|
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What is Otitis externa?
|
Swimmer's ear (infection of the ear canal)
|
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Polypeptides are composed of __________ linked amino acids
Peptides vs Proteins |
Covalently linked
peptide= less than 40 amino acids protein= more than 40 amino acids |
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Types of protein and peptide drugs. Name examples of the following:
Peptides Recombinant therapeutic proteins Blood products |
Types of protein and peptide drugs. Name examples of the following:
Peptides- Oxytocin, vasopression Recombinant therapeutic proteins- Human insulin, interferon Blood products- Factor x, Factor VIII, gamma globulin, serum albumin |
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Name the bacteria associated with:
Diphtheria Tetanus Whooping cough |
Name the bacteria associated with:
Diphtheria- diptheria toxin Tetanus- tetanus toxin Whooping cough- acellular pertusis |
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What are these therapeutic proteins used for?
Insulin Interferon beta Interferon gamma TPA |
What are these therapeutic proteins used for?
Insulin- diabetes Interferon beta- multiple sclerosis Interferon gamma- heart attack TPA |
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Is formation and stability of protein drugs based on covalent chemical bonding?
|
No. based on relative weak physical interactions
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Protein aggregation is often initiated by ___________ of protein monomer on the walls of the container
|
Adsorption
Aggregation also results from shaking or exposure to shear forces |
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Increased aggregation results in ___________
|
Precipitation
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Naturally forming drugs are in what form?
|
L-form
|
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Which amino acids are most prone to racemization
|
Aspartic acid
and Serine |
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Can proteins pass through transcellular or paracellular route?
|
YES
|
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name the order of epithelial cells from tightest to loose
|
skin> cornea> colon=conjunctiva> small intestine=nasal epithelium
|
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Name some solubility enhacing agents for proteins and peptides
|
polysorbate 20 or 80
sodium dodecyl sulfate these also prevent aggregation |
|
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What has a strong tendency to adsorb to interfaces thus used as an anti-aggregation agent
|
Human Serum Albumin (HSA)
|
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Give examples of Chelating Agents
|
used to reduce oxidation damage through binding of metal ions
Disodium EDTA Sodium sulfite or ascorbic acid are anti-oxidants that can also be added to reduce oxidation tendencies |
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Name preservatives used in multiple dosing vials
|
Benzyl alcohol
Phenol Buffered aqueous solutions are stable for 2 years in refrigerated conditions |
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Freeze-drying involves 3 stages:
Phase I Phase II Phase III What happens in each phase? |
Freeze-drying involves 3 stages:
Phase I-freeze solution at -35 to -40 C Phase II- Sublime at -35 C to remove frozen water Phase III- Residual water removed by lowing pressure and increasing temp to 20 C |
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Agents that raise glass transition temperature?
Used to help prevent proteins from caking or breaking during freeze-drying |
Mannitol
sucrose (not lactose) |
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How can protein drugs be sterilized?
a. autoclaving b. gas sterilization c. ionizing radiation d. not possible |
d. not possible
Manufacturing under aseptic conditions in class 100 area using HEPA filters |
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How can viruses be removed?
How can pyrogens be removed? |
virus-
filtration, precipitation, chromatography (remove) pasteurization, radiation, or cross-linking agents (inactivate) pyrogens- anion-exchange chromatography |
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What is the most common route of administration for proteins and peptide drugs?
|
Parenteral
|
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Diabetics become insulin resistant because of what?
|
high tissue protease activity
|
|
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Zn+2 ion speeds up or slows down the release of insulin?
|
slows down
|
|
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where are mannose receptors are present where?
Where are Galactose receptors found? |
alveolar macrophages
hepatocytes |
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Name some examples of PEGylated protein and peptide drugs?
|
PEG-Intron
Adenosine deaminase (ADA)- treats SCID L-asparaginase- treats lymphoblastic leukemia |
