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122 Cards in this Set
- Front
- Back
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ability of molecules to stick together to form an elastic layer on the surface of the liquid; this is why a metal pin or clop doesn't sink although denser than water
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surface tension
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Adhesion
vs Cohesion |
A-2 different materials
C-same material |
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Wetting
vs Drier Surfaces |
contact angle < 90 degrees
smaller the angle, the wetter the surface larger the angle, the drier the surface |
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system containign one or more constitiuents distributed throughout a homogeneous medium
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dispersion
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3 categories of dispersions
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True solutions= less than 0.001 micron
Colloids= 0.001 to 0.5 microns Coarse Dispersions= greater than 0.5 microns |
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particles are invisible even with the eletron microscope and pass through filter papter and semi-permeable membranes
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True Solution
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particles can't be seen with an ordinary microscope but can be seen witht eh eletron microscope; particles pass through filter paper but not semi-permeable membranes; particles diffuse less slowly than do the particles in a true solution
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Colloidal Dispersion
ex. Milk |
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particles often visible with the naked eye; will not pass through filter paper or semi-permeable membranes; particles seldom diffuse; extensively in pharmaceutical products
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Coarse Dispersions
ex: emulsions or suspensions |
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Dispersion Medium:Dispersed Phase
Gas:Gas Gas:Liquid Gas:Solid |
Dispersion Medium:Dispersed Phase
Gas:Gas- None Gas:Liquid-Fog Gas:Solid-Smoke |
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Dispersion Medium: Dispersed Phase
Liquid:Gas Liquid:Liquid Liquid:Solid |
Dispersion Medium: Dispersed Phase
Liquid:Gas- Foam Liquid:Liquid-Emulsion Liquid:Solid- Suspension |
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Dispersion Medium:Dispersed Phase
Solid:Gas Solid:Liquid |
Dispersion Medium:Dispersed Phase
Solid:Gas-Pumice Solid:Liquid- Gel |
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Surfactant:
Polar Group Non-polar group |
Polar:
Ionic- contains heteratom such as O,S,N,P as carboxylate , sulfate, ammonium, and phosphate Non-Ionic- contains Oh or -O- as polyalcohol or polyether Non-polar group: Hydrocarbon containing 12-20 carbone atoms |
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2 most important functions of surfactant
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1. they locate themselves at the interface of the two phases
2. they tend to make aggregates (micelles) |
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Lyophilc Colloids
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Lyophilic Colloids- react with dispersion medium; solvent loving; essentially one-phase system
Hydrophilic- water loving )mucilages) Alcophilic- alcohol loving helps increase viscosity of agents |
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Major repulsion mechanisms for surfactants
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Electrostatic interactions
and Steric repulsions |
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Lyophobic Colloids
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solvent hating: no attraction between the dispersed particles and the dispersion medium; usually are dispersions of inorganic particles or insoluble drug particles in water
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Association Colloids
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amphiphilic colloids; have a hydrophilic and lypophilic section; they form monomolecular films on the surface of water to cause a reduction in surface tension
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3 types of Colloids
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1. Lypophilc Colloids
2. Lyophobic Colliods 3. Association Colloids |
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Particle Size and Appearance
>1 micro m 0.1-1 micro m 0.05-0.1 micro m <0.05 micro m |
Particle Size and Appearance
>1 micro m- milky 0.1-1 micro m- blue-white (Tyndal effect) 0.05-0.1 micro m- Gray (semi-transparent) <0.05 micro m- Transparent |
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any procedure that reduces the size of the particles to colloidal range
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Dispersion Method
1. Ultrasonic Generators 2. Colloid Mills 3. Peptidation (addition of 3rd component to help dispersion) |
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spontaneous disperion of colloidal precipitate on the addition of small amounts of a third substance
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Peptization (deflocculation)
3rd substance usually is an electrolyte ex: sodium citrate added to calamine lotion to promote dispersion and prevent caking |
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Emulsion Creaming
vs Suspension Settling |
Creaming- Oil particle density < Aqueous medium density
creaming is usually reversible but not desirable Suspension settling- solid particles density > aqueous medium Suspension settling is reversible and irreversible |
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mixture of two substances, one dispersed in the other; particles are visible under microscope and can often be seen with the naked eye
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Suspension
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challenges with suspensions
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desirable particle size
caking of very small particles fast settling of coarse particles particle shape (symmetry) |
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Coagulation
vs Flocculation |
C- strong particle aggregation
F- loose particle aggregation |
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Equation of Sedimentation Rate
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Stoke's Equation
depends on: particle diameter particle density medium density gravity constant medium viscosity rate of settling |
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Properties of Colloids
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1. Kinetic Properties (brownian Movents- random movement)
2. Optical Properties (Tyndal Effect- light is scattered; used to determine size of particles) 3. Diffusion (Fick's Law- high to low conc.) 4. Sedimentation (Stokes law- density and radius are directly proportion to rate of sedimentation) 5. Viscosity (indirectly proportion to rate of sedimentation in stokes law) 6. Electrical Properties (colloids usually have elective charge- affects stability; like charges repel each other causing coagulation or flocculation not to occur) |
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difference in potential between the true surface of the particle and the area where the particles are uniformly distributed
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Nernst potential
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difference in potential between the outer edge of the fixed portion and the main body of the liquid
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zeta potential
(Most imoortant) |
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Sedimentation Rate with different in amounts of powder
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the more micro m of powder in water of powder in glucering the faster the settling rate
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colloids composed of tiny particles suspended in another immiscible (unmixable) marterial; suspension of two liquids that usually do not mix
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Emulsion
ex: oil and water |
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Nature of drug dictates the emulsion type:
W/O preferred when O/W preferred when |
W/O preferred when:
drug is water soluble skin needs to be softened O/W preferred when: drug is oil soluble easy removal fro the skin by water |
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Emulsion pros and cons
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pros- easy production, dose uniformity, patient acceptability, drug release
cons- instablility, medium for microbial growth, limited use, physical instability (coalescence, creaming) |
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Emulsion Stabilizers
help prevent flocculation, coalescence, and creaming |
1. Surfactants: ionic and non-ionic
2. Hydrocolloids: Acacia, gelatin, lecithin 3. Fine Solid: Colloidal clays (bentonite, magnesium, hydroxide) |
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Drugs goes to dispered phase
Emulsifyer goes to continuous phase |
Just Remember
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Hydrophilic Lipophilic Balance (HLB)
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Griffin
20x [Mw (hydrophilic portion)/ Mw (whole molecule)] Range from 0-20 100% hydrophilic: HBL of 20 100% lipophilic: HLB of 0 |
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Emulsion Stability
unstable if: |
dispersed phase upon standing tend to form aggregates
large aggregates rise to top or fall to bottom all or part of liquid of the dispersed phase seperates and forms a layer on the top or bottom of the emulsion as a result of coalescence microbial contamination and growth freezing and thawing |
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Creaming
vs Coalescence |
Creaming-reversible
Coalescence (emulsion breaking)- irreversible |
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High HLB
vs Low HLB |
high HLB- better for oil in water
low HLB- better for water in oil |
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HLB values for Emulsifiers
Antifoaming Emulsifiers (W/O) Wetting agents Emulsifiers (O/W) Typical Detergents Solubilizer |
Antifoaming- 103
Emulsifiers (W/O)- 3-6 Wetting agents- 7-9 Emulsifiers (O/W)- 8-18 Typical Detergents- 13-16 Solubilizer- 15-20 |
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material is resistant to the stomach acid; drug will be released at neutral pH of small intestine
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Enteric
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material is resistant to neutral pH; drug will be released at lower pH of stomach
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Reverse Enteric
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the more ____ the stronger th gel
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G-Blocks, juction zones
lG-block binds to Ca2+ and looses solubility/turns into gel |
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4 forces of swelling
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Polymer-solvent interaction
Electrostatic Forces Osmotic Forces Elastic Forces Replace H with K or Na to get more swelling; allows more water in |
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Monothilic
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Drug is released by diffusion out of a polymer matrix; release rate depends on initial drug conc. and relaxation of the polymer matrix
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Membrane
Drug release is controlled by permeable membrane Non-Porous vs Porous vs Filter orientation (Tortuosity) |
Non-Porous- drug diffuses through membranes
vs Porous- drug diffuses through membrane and pores vs Filter orientation (Tortuosity)- filler hinders the drug release |
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Osmotic Tablet
vs Osmotic Pump vs Solvent Evaporation |
Osmotic Tablet- constant release because only one outlet for drug
vs Osmotic Pump- water influx pushes drug out vs Solvent Evaporation- ? |
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Coacervation
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the seperation into two liquid phases in colloidal systems. the phase more concentrated in colloidal component is the coacervate, and the other phase is the equilibrium solution
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Simple Coacervation
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characterized by one polymer component induced by physical or chemical changes
temp Solubility pH Ionic Strength Conc. |
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Complex Coacervation
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involves more than one component; attraction of oppositely charged oolyelectrolytes
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aggregate of surfactant molecules, usually smaller than liposome
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Micelle
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microscopic phosopholipidbilayer vesicles
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liposomes
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Gastric Retention
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increases the drug absorption and hence its bioavailability; extends the absorption window
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Base Case Scenario
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Even Absorption
and Long Half-Life |
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the addition of a hydrophilic colloid to a hydrophobic colloid will ______ stability
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increase
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Examples of protective colloids
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gelatain, acacia, methylcellulose
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relates to the lowest levels of drug that can be measured; practically the smallest amount of drug or metabolite that can be determined
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Sensitivity
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the ability of an assay to distinguish a drug from its metabolites, other drugs and /or endogenous constituents of biologic fluids
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Selectivity
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Need for biopharmaceutical Analysis
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biovailability and bioequivalence studies
new drug development drug abuse problems clinical pharmacokinetics research in basic biomedical and pharmaceutical sciences |
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defined as parts-per-million or less concentrations of drugs
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Trace Levels
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Metabolism reactions
Phase 1 Phase 2 |
Phase 1-typically involves oxidation, reduction, hydrolysis
Phase 2- entails coupling or condensation of drugs of their phase 1 metabolites with body constituents |
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an assay must be able to distinguish readily between ___________ and _________
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parent compound
and metabolite |
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Precision
vs accuracy |
repeatability
degree of closeness of measurement to the actual true value |
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Limit of detection
Ruggedness range and Linearity |
Limit of detection- only detect within certain range
Ruggedness- ability to reproduce procedures in dif. labratories in different location range and Linearity- used for comparison |
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USP-NF
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used for pharaceutical testing of official substances; ex: production of new OTC drug
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Separation and Purification Techniques
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Protein precipitation and denaturation
Biological Samples: solvent extraction lyophilization hydrolysis of conjugates homogenization chemical derivatization Chromatographic methods: Thin layer chromatogrphy (TLC) Gas chromatography (GC) High performance liquid chromatography (HPLc) Gel permeation chromatography (GPC) Ion Exchange Chromatography |
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a seperation technique based on differing affinities of a mixture of solutes between two phases
results in physical separation of the mixture into various components mixture is separated by distributing the components between a stationary phase and a mobile phase |
Chromatography
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chromatography that uses a charged stationary phase to separate charged compounds
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ion exchange
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chromatography that is an elution procedure used in liquid chromatography in which the mobile phase is significantly more polar than the stationary phase
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Reversed phase
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seperates molecules according to their size
smaller molecules take longer to elute larger molecules elute faster |
Size Exclusion chromatography
aka gel permeation chromatography or gel filtration chromatography |
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Detection Methods
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Spectrophotometry methodology
Fluoremetry and Phosphometry Flame Ionization Detector (FID) Electron Capture detector (ECD) Mass Spectrometer (Ms) |
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Qualitative Analysis
Quantitative Analysis |
Qualitative Analysis- retention values
Quantitative Analysis- detector responses |
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External Standard
Internal Standard Standard Addition |
External Standard-spike increasing conc. in fluids; plot responses against conc.
Internal Standard- P-C behavior similar to drug or metabolite; response ratios are determined Standard Addition- good for quantitation or analyzing compounds close to their sensitivity limit |
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Note about External Standard
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same retention time, but height of peak varies with different concentrations
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elution procedure used in liquid chromatography in which the mobile phase is significantly more polar than the stationary phase
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Reversed-Phase Chromatography
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type of chromatography that uses a charged stationary phase to separate charged compounds
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ion exchange chromatography
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What is cGMP?
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governments quality standards that are intended to protect the public from harmful and unsafe drugs, medical devices, food and cosmetics
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cGMP established by
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US Food Drug and Cosmetic Act of 1938
applies to domestic and to foreign suppliers and manufacturers |
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Purpose of cGMP
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to make sure food we eat is SAFE
manufactured under SANITARY conditions medical devises used are SAFE and EFFECTIVE prepared form APPROPRIATE ingredients all foods, drugs, medical devices and cosmetics are truthfully and informatively labeled |
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cGMP code of regulations listed in _____ CFR, Part ___ and _______
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cGMP code of regulations listed in 21 CFR, Part 210 and 211
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Seven Expectations of all GMPs
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1. Protect the product from contamination
2. Prevent Mix-ups 3. Know what you are doing before you do it 4. Strive for consistency and control 5. Document all activities 6. Have an independent group make final decisions on documents, product release and quality issues 7. Learn from mistakes; monitor and continually improve |
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Dispersed Phase AKA what?
Continuous Phase AKA what? |
solute (extermal)/ minor phase
solvent (internal)/ major phase |
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Manufacturing
vs Compounding |
M- larger scale
C- single prescription |
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Reason for compounding comeback
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-drug doses or forms not commercially available
-acceptable to kids -some medications are not very stable -not manufactured/approved yet -trying products in innovative ways -veterinary drugs -home health care -allergic to excipients |
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Standards and Regulations For Compounding
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Food and Drug Modernization Act of 1997
and USP/NF |
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a system containing one or more constituents distributed throughout a homeogeneous medium
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dispersion
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3 categories of dispersions
True solutions Colloids Coarse dispersions |
True solutions- less than 0.001 mocrin
Colloids- 0.001 to 0.5 microns Coarse dispersions- greater than 0.5 microns |
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particles are invisible even with the electron microscope and pass through filter paper ans semi-permeable membranes
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True Solution
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Particles can't be seen with an ordinary microscope but can be seen with the electron microscope; passes through filter paper but will not pass through semi-permeable membranes
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Colloid Dispersion
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particles are visible with the naked eye; will not pass through filter paper nor semi permeable membranes
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Coarse Dispersion
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Lyophilic Colloids
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react with the dispersion medium so solvent loving
strongly attracted to the dispersion medium |
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Lyophobic Colloids
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solvent hating; no attraction between the dispersed particles and the dispersion medium
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Association Colloids
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amphiphilic colloids; have hydrophilic and lypophilic protion
they form monomolecular films ont he surface of water to cause a reduction in surface tension |
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Dispersion Methods; any procedure that reduces the size of the particles to the colloidal range
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1. Ultrasonic Generators
2. Colloid Mills 3. Peptization 4. Electrolytic disintegration |
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Peptization (deflocculation)
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spontaneous dispersion of a colloidal precipitate on the additions of small amounts of a third substance is known as peptization
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Kinetic Properties of Colloids
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particles under 0.5 microns which are in the colloidal range will show randome movement in a dispersion medium= BROWNIAN MOVEMENTS
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Optical Properties of Colloids
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The Tyndal Effect: no visible cone when ligh is shone through a true solution
Light is scattered by colloidal particles |
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Diffusion of Colloids
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Fick's Law: particles have tendency to diffuse from a region of high concentration to a region of low concentration
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Sedimentation of Colloids
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particle will settle if particles has greater density than that of the dispersion medium
Stoke's Law= relates velocity, radius and viscosity to evaluate sedimentation |
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Viscosity of Colloids
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the measure pf the resistance of a liquid to flow
lyophobic and hydrophobic colloids do not affect the viscosity lyophilic and hydrophilic colloids do affect viscosity |
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Electrical Properties of Colloids
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usually charged
causes stability coagulation and flocculation does not occur |
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ions in solution that surround the colloid particle to balance the charge on the surface are called what?
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Gegenions or counterions
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potential on the surface of the particle is known as the what?
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Nernst potential
= difference in potential between the true surface or the particle and the area where the particles are uniformly distributed |
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difference in potential between the outer edge of the fixed portion and the main body of the liquid
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zeta potential
Most important potential |
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zeta potential can be lowered by adding what?
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adding an ion of opposite charge to that on the colloid particle
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Protective Colloids
Examples: |
the addition of hydrophilic colloid to a hydrophobic colloid will increase stability
Examples: Gelatin Acacia Methylcellulose |
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the outer layer of counter ions is called
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Gouy-Chapman layer
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condition of fixed surface charge surrounded by more loosely held counter ions is known as the what?
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Electrical or Helmholtz double layer
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stage or process by which the physical, chemical, and mechanical properties of drug substances are determined by themselves and with common excipients
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Preformulation
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Objectives of preformulation
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to demonstrate that the drug product is safe and effective
-selection of most suitable drug -identifying compatible excipients |
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Reasons for molecular optimization include:
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improvement of stability, solubility, absorption, nd changing crustallinity, taste, odor, etc.
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Different Bulk Charactierization
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-Crystallinity
-Hygroscopicity -Fine particle characterization -Bulk density -powder flow properties -mechanical properties |
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Difference among:
Crystallinity Polymorphism Amorphous |
Crystallinity-spacing in 3-dimentsional array
Polymorphism- ability to exist as more than one distinct crystalline species Amorphous- atoms are randomly placed as in a liquid, higher thermodynamic energy |
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Techniques for determining polymorphism
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Thermal Methods (DSC)
X-ray Diffraction IR spectroscopy Solid state NMR |
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Hygroscopicity
vs Deliquescent |
Hygroscopicity- tendency to absorb atm moisture
Deliquescent=- absorb sufficient water to dissolve completely |
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Parameters and Methods for particle characterization
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Parameter:
Size Shape Surface Area Methods: Microscopy, sieving Brunauss, Emmett and Teller (BET) |
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What is the difference b/w
Bulk density Apparent/Tap density True density |
Bulk density- total inventory for calculating storage compacity
Apparent/Tap density- mass/volume for capsule preparation True density- minus the air; smallest density volume of the three |
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Rationale for Powder Flow
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Free flowing
Non-free flowing (cohesive) Generally, a free flowing material is preferred |
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Mechanical Properties of powders
Compressiblity vs Compactibility |
compress- reduction in volume
compact-pressure w/o chipping; no elasticity |
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Solubility Analysis
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Determination of pKa
Lipophilic nature solubility in various temperature and media pH solubility profiles |
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Stability Analysis needed for what?
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Compatibility
Packaging material usually done at room temperature vital information for labeling, storage, exp. date, packaging and shipping |
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Physicochemical properties:
what are the effects on solubility? -endothermic -exothermic -high crystal comp -low crystal comp what is the effect on bioavailablitly -high solubility |
Physicochemical properties:
what are the effects on solubility? -endothermic: increase temp=inc. solubility -exothermic: increase temp=dec solubilitly -high crystal comp: inc solubility -low crystal comp: decreases solubility what is the effect on bioavailablitly -high solubility= high bioavailability |
