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122 Cards in this Set
- Front
- Back
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the science that deals with the dosage forms design, which includes formulatiom, manufacturing, stability and effectiveness of pharmaceutical dosage forms
the science that converts a drug into a medicine |
Pharmaceutics
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the physical form in which the drug is available for administration
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Dosage Form
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means of administering drugs to the body in a safe, efficient, reproducible and convenient manner
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Drug delivery system
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Dosage form from simple to complex
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Solutions
Capsules Tablets Ointments, Creams Transdermal systems Inhalation Products Liposomes Drug eluting stents |
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Disadvantages of Buccal and Sublingual route
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unacceptable palatability for bitter drugs
dissolution problems for dry mouth conditions possibility of swallowing drug load might be limited (only smaller dose can be administered) |
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the more rapid and complet the absorption, the more _______ and ________ the pharmacological response becomes
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the more rapid and complet the absorption, the more uniform and reproducible the pharmacological response becomes
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process by which a drug enters the blood stream without being chemically altered
or movement of a drug from its site of administration into the blood or lymphatic system |
Absorption
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4 Steps of Absorption
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1. Delivery of drug to its site of absorption
2. Getting the drug into solution 3. Movement of dissolved drug through the absorption membranes 4. movenment of the absorbed drug away from the site of absorption into the general circulation |
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Organs with low surface area
Organs with high surface area |
eye, nasal, buccal, rectum, stomach, large intestines
small intestines, lungs |
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thickness of absorption membrane
put in order: sublingual, buccal, nasal, vaginal, epithelial |
Thickest to Thinnest
buccal vaginal- sublingual epithelial nasal |
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pH of:
Oral Cavity Stomach Small Intestine Colon Rectum |
Oral Cavity~ 7
Stomach~ 1.5-6 Small Intestine~ 6-8 Colon~ 5.5-8 Rectum~ 7 |
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What things delay gastric emptying, causing a longer onset time
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fatty foods
viscous food cold drinks anticholinergics narcotics laying on left sisde will slow down absoprtion |
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Time for drug to pass through stomach and intestine
Fasting: Fed: |
Fasting: 4-8 hours
Fed: 8-12 hours |
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Intestinal flow is _______ than gastric flow
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greater
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Food decreases or increases absorption of drugs?
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Both
decrease absorption of antibiotics but in general it delays gastric emptying and can reduce the rate and extent of absorption |
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Dosage forms that do not require disintegration or dissolution
Dosage form that requires dissoltion, but not disintegration |
Solutions
Syrups Injections Suspensions and emulsions |
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Exipients that increase and decrease dissolution
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Increase:
Disintegrants Lubricants Surfactants Buffers Complexing agents Decreases: Vehicles Binders, granulating agents, and coating agents Diluents, coloring, nd flavoring agents |
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Affect of lipophilic and hydrophilic properties on dissolution
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Lipophilic- decrease dissoltion
Hydrophilic- increase dissoltion |
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Noyes-Whitney Equation
dC/dt= D A (Cs-Cg)/h |
describes dissoltion rate based on physiochemical fators that affect it like:
diffusion coefficient surface area pf drug particles thickness of diffusion stagnant layer of solvent around the drug particle saturation solubility of teh drug in the diffusion layer concentration of the drug in the bulk solution of the gut |
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Difference between hydrophilic and lipophilic drugs on effective surface area for smaller particles
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Hydrophilic: smaller particle= increases effectiveness on surface area
Lipophilic: smaller particle= decrease effective surface area |
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The salt form of the drug is more or less soluble than the nonionized form of teh drug
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Solubility
Salt > nonionized form ionized > nonionezed |
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As the pH increases from stomach to intestines, the solubility of:
weak acids weak bases |
weak acids- increases solubility
weak baes- decreases solubility |
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Affect of polymorphism on solubility and stability
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Amorphous form is more soluble, but less stable
aged products with more stable polymorph form are less soluble and reduce bioavailability amorphous more soluble than crystalline form |
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drugs mixed with solvent form?
drugs mixed with water form? |
solvates
hydrates |
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absorption occurs under ______ conditions
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sink conditions (high concentration gradient)
bulk solution concentration is much smaller than saturated solubility of drug in diffusion layer |
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Pathways for Drug Transport
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Trancellular Transport:
1. passive Non-ionic diffusion (simple)- most drugs 2. passive channel-mediated transport (small water soluble drugs) 3. Carrier mediated transport -facilitated diffusion (conc gradient) -Active transport (against conc gradient) Paracellular Transport (Aqueous) small polar substances smaller than 500 Da |
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Factors influencing drug Absorption
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1. Anatomical and Physiological Factors
2. Dosage Form Factors 3. Physiochemical Factors of Drug 4. Pathways for Drug Transport 5. Biochemical Factors |
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sterile and pyrogen-free preparations injected through skin into one or more layers of skin, or into internal body compartments
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Parenterals "injectables"
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free from viable microorgansims
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sterile
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free from fever producing organic substances
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pyrogen-free
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What type of solutions and emulsions can be injected?
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clear
aqueous non-precipitating isotonic pyrogen-free |
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USP limits for Large and Small volume
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Large:
<50 particles (>10/ml) <5 particles (>25/ml) Small: <10,000 particles (>10/ml) <1000 particles (>25) |
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Intra-arterial
Intra-articular Intracardiac Intraspinal Intrasynovial Intrathecal |
Intra-arterial: injected into arteries
Intra-articular: injected into the joints Intracardiac: injected into heart chamber Intraspinal: injected into spinal column Intrasynovial: injected into joint-fluid (synovial fluid) Intrathecal: injected into spinal fluid |
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the most difficult dosage form to formulate
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suspensions
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a dispersion on one immiscible liquid in another using emulsifying agent
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Emulsions
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Type of emulsions used for:
SC inj IM inj TPN preparations |
SC inj- W/O emulsion
IM inj- O/W emulsion TPN preparations- lipid emulsion |
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USP types of injections
Drug injection Drug for injection Drug injectable emulsion Drug injectable suspension Drug for injectable suspension |
USP types of injections
Drug injection- ready liquid preparations of drug in a solution form Drug for injection- dry solid the require the addition of suitable vehicle to yield solution similar to inection Drug injectable emulsion- Ready liquid preparation of drug substances dissolved or dispersed in a suitable emulsion medium Drug injectable suspension- Ready liquid preparation of solid drug substances suspended in a suitable liquid medium Drug for injectable suspension- Dry solid that require the addition of suitable vehicle "reconstitution" to yield preparation similar to injectable suspension |
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Name location of injection and volume that can be injected:
Intramuscular Subcutaneous Intradermal |
Intramuscular- skeletal muscle; max 5 ml in buttock and max 2 ml in deltoid muscle; 20-22G
Subcutaneous- loose interstitial tissue; max 2 ml; 24-26G Intradermal- skin; max 0.1ml;23-26G |
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Vehicles for Injection:
Sterile water Bacteriostatic water sodium chloride dextrose bacteriostatic sodium chloride ringer's injection lactated ringer's injection |
Vehicles for Injection:
Sterile water- for reconstitution; not for I.V. administration Bacteriostatic water- contains antimicrobial agents; not for newborns; for reconstitution; only small volume <5 mL sodium chloride- for reconstitution, IV administration, 2 mL to flush the IV lines after each use or every 8 hrs if not used dextrose- isotonic; for reconstitution and IV administration bacteriostatic sodium chloride- for reconstitution of onluy small volume <5 mL; for flushing IV lines; not for use in newborns ringer's injection- for reconstitution and for IV administration; isotonic; contains NaCl, KCl, CaCl2 lactated ringer's injection- contains sodium lactate with other electrolytes; used as replenisher and systemic alkalizer |
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When to use non aqueous vehicles
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when drug substance has limited water solubility or stability
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atleast 1 antimicrobial preservative required for mutlidose containers
examples of these antimicroial preservatives are? |
Benzethonium chloride and benzalkonium chloride 0.01%
Chlorobutanol, phenol, and cresol 0.5% |
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Buffers used to keep IV, IM, and SC pH in range?
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IV: 3-10.5 pH
IM/SC: 4-9 pH salts of citrate, acetates, phosphates |
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The air in multiple-dose preparation should be frequently replaced with what?
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inert gas such as nitrogen
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Exampls of Solubilizers
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ethanol, glycerin, PEG, tween 80, Cyclodextrins
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Tonicity modifiers
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NaCl and dextrose
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Chelating agent
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used to inactivate metals
EDTA |
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Protectants
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used to protect against degradation of the drug
sucrose and trehalose and HSA |
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Three Sterilization Methods
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1. Thermal
2. Mechanical (pore size of 0.22 micrometer) 3. Chemical |
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Dry powder is prepared by?
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lyophilization (freeze drying)
crystallization spray-drying |
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USP allows for overages in excess of the labeled size or volume of single dose and multiple dose containers
how much excess for 50 or more size? |
2% for mobile liquids
3% for viscous liquids |
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Typical volume size for withdrawal:
single dose container Mulipler dose container |
single- 1 L
multiple- 30 mL; usually about 10 doses per vial |
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Sterility Testing USP 71
Pyrogen Testing Particulate Matter Testing Container/Closure Integrity Testing |
Sterility Testing USP 71- confirm absense of microorganisms using biologic indicators/ strip of filter paper
Pyrogen Testing- tests for thermostable pyrogens that remain in water, they can be removed by oxidizing them using: potassium permanganate; Rabbit's Test USP 151- temp did not increase by 0.5 ceclius, total temp can not rise more than sum of 3.3 celius for 5 rabbits; Bacterial Endotoxin USP 85- LAL Particulate Matter Testing- dust, fibers, glass fragments inspected visually or automatically, product is passes against light source Container/Closure Integrity Testing- immerse in dye, apply negative pressure for 15 min, release rapidle, just used for ampules |
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HEPA filters remove
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99.99% efficient
0.3 micrometer particles |
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Reasons for liquid preparations
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1. Easier to swallow
2. Only suitable dosage form 3. Irritation 4. Flexibility- more drug combinations and dosage forms 5. Immediate drug availability |
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Liquid preparation that contain one or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvents
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Pharmaceutical Solution
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aqueous solutions containing sugar
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Syrup
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sweetened hydroalcoholic solutions
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Elixir
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Alcoholic solutions of aromatic materials
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Spirits
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Aqueous solutions of aromatic materials
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Aromatic waters
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Solutions prepared by extracting active constituents from crude drugs
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Tinctures or Fluidextracts
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Can soltions be aqueous or non-aqueous?
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yes
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disadvantages of solutions
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chemical stability
microbial growth bulky more pronounce distaste potential dosing errors |
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3 main steps of dissolution
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separate particles of solute in the crystal
separate molecules of solvent energy needed with interaction |
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used to increase aqueous solubility of weak electrolytes and non-polar molecules
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Co-Solvents
ex: Propylene glycol PEG Glycerin Alcohol |
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measure of polarizability of a molecule
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Dielectric constant
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Rate of dissolution depends on?
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free surface energy and shape of particle
temperature type of agitation amount of material already in solution viscosity and volume of solvent concentration of the dissolved solute |
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What are sink conditions?
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if Ct << Cs
Ct= Concentration at time t Cs= Concentration at saturation |
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Purpose of Noyes-Whitney Equation
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Equation for rate of weight loss of particle per unit time
R= KS (Cs-Ct) diffusion coefficient surface area conc at saturation conc at time t K=D/h D= diffusion coefficient h= thickness of diffusion layer |
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How do we get insoluble organic weak acids and bases to mix readily in slution with water?
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form water soluble salts by using either strong acids or strong bases
solubility of these salts depends upon the pH; could cause it to precipitate if too much added |
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Rules for solubility
Inorganic and Organic |
Inorganic:
both are monovalent one is monovalent salts of Na, K, Li quaternary ammonium salts Nitrates, Nitrites, acetates, chlorates, lactates sulfactes, sulfites, thiosulfates chlorides, bromides, iodides sulfides- insoluble hydroxides and oxides- insoluble phosphates, carbonates, silicates, borates, hipochlorites- water insoluble Organic: one polar functional group=soluble to total chain length of five carbons |
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Fixed Oils
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Almond
Peanut Sesame Cottonseed Soybean |
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Volatile oils
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Wintergreen
or Turpentine |
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Ways to purify water
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1. Distillation
2. Ion-exchange 3. Reverse osmosis |
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Water-insoluble synthetic polymerized resins used for Ion-Exchange
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1. Phenolic
2. Carboxylic 3. Amino 4. Sulfonated |
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What is Type 1 and Type 2 glass
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1- highly resisant borosilicate glass
2- treated Soda-lime glass Used for packaging sterile water for irrigation |
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Examples of Bacteriostatic agents
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Thimerosal
Phenylmercuric nitrate chlorobutanol Phenol Cresol methyl para hydroxy benzoate propyl para hydroxy benzoate benzyl alcohol benzalkonium chloride |
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Rubbing alcohol contains what?
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70% V/V of ethanol
each 100 ml contains 355 mg of sucrose octaacetate 1.4 mg of denatonium benzoate |
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Basic composition of any syrup
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sugar or sugar substitute
Preservative flavors colors 85g sucrose in 100 ml of syrup |
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Agents other than sucrose used to prepare syrups
What is used for diabetics? |
1. Detrose
2. Glycerin 3. Sorbitol hydroxyethylcellulose or methylcellulose |
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What is inversion?
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when di-saccharides are hydrolyzed by heat into two monosaccharides
resulting combination are invert sugars |
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Ways to prepare syrups
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1. Solution with aid of heat
2. Solution by admixture in the cold (not heat/ just shake) 3. Dissolution of sucrose in a medicated or flavored liquid 4. By percolation (water passes slowly through a column of crystalline sucrose to dissolve it) |
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Examples of syrups prepared by percolation
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1. Syrup
2. Tolu Balsam Syrup 3. Ipecac Syrup |
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Glycerin is a stabilizer
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True
Used as an emetic in poisonings |
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4 Methods for preparing spirits
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1. Simple Solution
2. Maceration 3. Distillation 4. Chemical Reaction |
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Primary solvents or vehicles found in elixirs
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water
alcohol glycerin propylene glycol |
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examples of medicated elixirs
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Antihistamine elixirs
Sedative and hypnotic elixirs Expectorants cardiotonic elixirs |
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Isotonic solutions equal what percent sodium chloride
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0.9 % NaCl
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What are Tinctures and Fluid Extracts?
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Products prepared by extraction
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Two prinicple methods of extraction
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1. Maceration- uses menstruum (extracting solvent)
2. Percolation- powdered drog is extracted by the slow passage of a suitable solvent through a column of the drug |
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What are the following?
Percolator Marc Percolate |
Percolator- extraction vessel
Marc- residue remaining after extraction Percolate- liquid extract |
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liquid preparations of vegetable drugs containing alcohol
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Fluidextracts
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Examples of Fluidextracts
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Cascar Sagrade Fluidextract
Senna Fluid extract Aromatic Cascara Fluidextract |
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solution of pyroxylin dissolved in a mixture of ethanol and ether
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Collodians
when solvent evaporates a water impervious layer is left on the skin over the wound or sore |
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3 Common Collodion products
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Collodion USP
Flexible Collodion USP Salicylic acid Collodoin USP |
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consist of primary particles existing individually of with some loose agglomeration through adhesive forces
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Powders
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consist of large particles formed by joining of binding together of primary particles whose identity can still be visible in the final agglomerate form
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agglomerates
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consist of particles formed by the progressive enlargement of primary particles until their original identity is no longer visible
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Granules
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spherical particulates produced during a precise forming and mechanical handling
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Pellets
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Powders vs granules
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Powder- small particles with known identity
Granules- enlarged particles, with unknown identity |
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Advantages and Disadvantages of Powders
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Advantages:
more stable in solid state no difficulty swallowing easy to adjust dose can have rapid onset of action feasible to be made into other dosage formulations Disadvantages: patient could misunderstand dose bitter tasting drug difficult to protect from decomposition expensive to make lack convenience of handling leack ease of identification lack ease of administration by patient |
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science and technology of small particles
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Micromeritics
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Methods to determine particle size
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Sieves
Optical Microscopes Electron Microscope Sedimentation method centrifugation method light scattering method |
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Higher sieve number means
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finer powder
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Official USP definition of Powders for animals and vegetables
Very course coarse Moderately course fine Very fine |
Very course- 8
coarse- 20 Moderately course- 40 fine- 60 Very fine- 80 |
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Particle size reduction on large scale
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Ball mill
Hammer mill granumill |
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Rhombohedral
vs Cubic Packing |
Rhombohedral is more ideal because it has less percent porosisty
large spaces of cubic packing allow for other particles to get in and cause packing |
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Equation for Bulkiness
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Bulkiness = 1/Density
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Bulkiness increases as particle size _________
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decreases
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Granules flow _____ than powders
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better
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Reasons for granulation
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better flow
better compression more uniform longer shelf-life greater stability decrease caking more easily wetted by a liquid |
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Examples of Diluents or fillers
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Lactose
Microcrystalline cellulose (sugar-free) Modified Dextrose |
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Examples of binders
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Starch
Polyvinylpyrrolidone (PVP) |
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Examples of Lubricants
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prevents formulation from sticking to machinery
Magnesium stearate Talc |
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Examples of Glidants
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improves flowability
Silica derivatives Talc |
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flavors vs sweeteners
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flavors- longer shelf-life
sweeteners-short shelf-life, but more potent |
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Accubreak Technology
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tablet that you can break in half and have exactly expected dose of drug on each half; no active ingredient in center of tablet
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Desyrel
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Tablet is scored so that it can be broke into thirds or in half
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Methods of Tablet Preparation
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Direct compression
Wet Granulation Slugging (dry granulation) Novel Methods |
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problems with high dose drugs
problems with low dose drugs |
high- compressibility
low- content uniformity |
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What is slugging
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Dry granulation method
compact large masses of powder mixture, crush and size pieces into smaller granules, lubricate tablet, active or diuent must have cohesive properties, drugs that degrade in moisture or heat |
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Problems in Tableting
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Capping
Improper fill Picking or sticking Crumbling Mottled tablets non-disintegrating tablets |
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Disintegration Testing
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Basket rack device
operates by reciprocating action disintegration fluids include water, gastic fluid, intestinal fluid, buffer solution record time required for disintegration |
