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230 Cards in this Set
- Front
- Back
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What is the dispersed phase?
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Substance that is distributed
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What is the dispersion medium?
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Vehicle in which the substance is distributed
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Describe a molecular dispersion
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Example: Solution
particle size <1nm Transparent physical appearance This is not technically a dispersed system. |
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Describe a colloidal dispersion.
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Example: Gel
Particle size 1nm - 0.5um Transparent or cloudy appearance |
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Describe a coarse dispersion
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Example: suspension/emulsion
particle size 0.5-50um Cloudy or opaque appearance |
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Order coarse dispersion, molecular dispersion, and colloidal dispersion from smallest particle size to largest
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Molecular --> colloidal --> coarse
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Describe the stability of a dispersed system.
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More stable chemically - Molecules are protected from degradation "strength in numbers".
Less stable physically - Larger particles will separate or sediment due to gravity |
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What is the definition of a gel?
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A semisolid system consisting of dispersions made up of either small inorganic particles or large organic molecules enclosing and interpenetrated by a liquid
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What is a hydrogel?
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When the dispersion medium is water
Example: Pluronic gel |
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What is an organogel?
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When the dispersion medium is an organic liquid
Example: Lecithin, OH, isopropyl palmitate |
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What does lyo mean?
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It is the prefix for solvent
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What does lyophobic mean? Describe the characteristics of something lyophobic
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Solvent fearing.
1) Difficult to prepare 2) Less stable 3) more likely to precipitate from the mixture |
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What does lyophillic mean? Describe the characteristics of something lyophillic
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Solvent loving
1) Easy to prepare 2) More stable 3) Less likely to precipitate out |
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How is a gel formed?
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1) Disperse the polymer in a vehicle (separate polymers)
2) Reconnect the polymers. They will form a gel by trapping liquid |
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What are the types of gels? describe them.
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Single phase gel - looks transparent or clear. Has no apparent boundaries between the dispersed phase and the liquid
Two phase gel - opaque. Gel mass consists of a network of small discrete particles |
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What is a mucilage?
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A single-phase gel prepared from natural gums (acacia)
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What is a jelly?
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A single phase gel that is mostly liquid.
i.e. contraceptive jellies |
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What is a magma?
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Two-phase gel consisting of relatively large particles
i.e. Bentonite magma that we used to make calamine lotion |
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What are the physical properties of a gel? Describe them.
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1) Syneresis: Gel network "shrinks" and forces out dispersion medium (gel bleeding)
2) Swelling: Gel network absorbs moisture from the air and increases volume, changes viscosity. Increases volume, decreases concentration. 3) Imbibition: Gel network absorbs moisture from the air with no significant increase in volume Decreases viscosity and physical stability |
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What are the uses of gels?
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Topical administration of drugs
Suspending and stabilizing agent |
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What are some advantages of gels?
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1) High degree of clarity
2) Easy to apply and remove 3) Fast release of drug substances 4) Non acnegenic |
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What is Retin-A?
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Gel formed for acne, cream for wrinkles
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Wtf does rheology mean?
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The study of the flow of liquids and deformation of solids
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What does viscosity mean (n)?
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The resistance of a fluid to flow.
The higher the resistance, the greater the viscosity. |
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What units is viscosity measured in?
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poise (ps) = g/cm sec OR
centipoise (cps) = 0.01poise OR millipascal seconds |
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What centipoise does a semisolid usually have?
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Around 1500-2000 centipoise (cps)
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How do we measure viscosity? Describe them
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Using a viscometer!
1) Capillary method - time measured for fluid to move a determined distance 2) Resistance method - Amount of force need to move paddle through liquid |
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What is a newtonian system?
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A system in which viscosity stays constant as force/stress is applied
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What is a non-newtonian system?
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Viscosity changes as force/stress is applied
Thixotropy Viscosity increases while sitting and decreases when agitated Helpful for suspending agent Sits = semisolid Mixed/shaken = liquid |
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What are the factors that affect viscosity?
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1) pH
2) Addition of salts 3) Temperature |
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Know how to calculate effect of temperature on viscosity page 60!
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Know how to calculate effect of temperature on viscosity page 60!
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What is a polymer?
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Molecules made up of repeating units called monomers.
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Most gels are prepared from ________?
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most gels are prepared from POLYMERS.
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What are some examples of polymers used in pharmacy?
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1) Methylceullose (higher # = higher # of monomers)
2) Carbopol 3) Polyethylene glycol (PEG) (higher # = higher MW) |
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What is a suspension?
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Preparation containing finely divided drug particles disturbed uniformly throughout a vehicle in which the drug exhibits a minimum degree of stability.
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What are two forms suspensions come in?
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Either as a ready to use product OR
A powder for reconstitution |
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Why should you use a suspension?
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1) Stability
2) Insoluble drug 3) Good to be used orally. Taste masking/ease of swallowing 4) Can be used topically (ointments, lotions, mucosal membrane) 5) Can be used parenterally (IM or SC injection) |
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Describe the stability of a suspension
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Drugs are more stable chemically in suspension (than a gel)
Less stable physically |
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Why would a suspension be good to use for an insoluble drug?
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A drug that is insoluble in water will often erratically or incompletely dissolved.
Suspensions fix this. |
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What are the advantages of an oral suspension?
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1) Good taste masking
2) Ease of swallowing |
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What can parenteral suspensions NOT be used for?
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NOT FOR IV INJECTION
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What does a suspension contain?
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Dispersed phase and dispersion medium
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What is important for the dispersed phase?
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Particle size is important!
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A dispersed medium contains what?
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1) Stabilizing agent
2) Suspending agent 3) Wetting agent 4) Preservative 5) Flavorant 6) Sweetners 7) Colorants |
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What does a stabilizing agent do? examples?
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Decreases attraction between particles
i.e. citric acid, sodium citrate |
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What is a suspending agent? example?
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Increases viscosity to decrease sedimentation
i.e. guar gum, xanthum gel, methylcellulose |
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What is a wetting agent? examples?
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Decreases interfacial tension between particles and dispersion medium to allow for more effective mixing
i.e. polysorbate 50, glycerin |
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Know how to use stokes law on page 63-64
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Know how to use stokes law on page 63-64
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What are some methods to decrease sedimentation rate? What are some things you should keep in mind when changing these?
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1) Increase viscosity (but still must be able to pour and redisperse suspension)
2) Decrease particle size (diameter of 1-50um, very small particles will cake easily) |
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What are the rules for a pharmaceutically elegant suspension?
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1) Settle slowly and are easily redispersed upon gentle shaking of the container
2) Particle size remains constant over time 3) Should pour readily and evenly from the container |
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How should you package a suspension?
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1) Wide-mouth container large enough to allow adequate mixing of the solvents
2) Tight containers 3) Protects from freezing, excessive heat, and light 4) HAVE A SHAKE WELL LABEL |
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Describe the phases a suspension goes through as it expires.
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1) Flocculation: Loose aggregation of particles held together by comparatively weak particle bonding forces
2) Agglomeration: Particles form larger crystals or masses 3) Caking: Dispersed phase completely settles to the bottom of the container |
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How are attractive forces between particles minimized in a suspension?
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By using a stabilizing agent!
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Describe the process of preparing a suspension.
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1) Add wetting agent to the drug if needed (alcohol, glycerin, etc)
2) Mix well using a mortar and pestle or blender 3) Add dispersion medium (including flavor, color, preservatives, etc) in portion and mix well after each portion is added 4) Rinse mixing equipment with vehicle and add to suspension 5) q.s. to the final volume |
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What factors should you consider when preparing a suspension?
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1) Drug may only be available in capsule or tablet form
2) Drug is usually more stable in a dry solid form than in suspension 3) Age or condition of the patient may limit use of certain excipients (don't use preservatives in neonates and preterm infants, flavoring and coloring agents are unnecessary if the suspension will be administered through a feeding tube. |
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What is a sustained-release suspension called? Describe how it works!
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Pennkinetic system
1) Ionic drug is complexed with ion-exchange resin complex 2) Drug-resin complex are coated with ethyl cellulose and suspended in a liquid dosage form 3) Drug is slowly released by ion-exchange in the GI tract examples: Tussionex pennkinetic extended-release suspension (medeva) lasts 12 hours |
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What is an emulsion?
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A uniform mixture of two immiscible liquid phases, one of which is dispersed in the other phase
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What are the two types of emulsions regarding the liquid phases
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Oil in water o/w
or water in oil w/o |
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What is a macro emulsion? Microemulsion?
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Macroemulsion = 10-50um droplet diameter (99% are these!)
Microemulsion = 0.01-0.1um droplet diameter |
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What do emulsions contain?
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1) Dispersed (internal phase): Contains active drug
2) Continuous (external phase) 3) Emulsifying agent: KEY INGREDIENT, makes emulsion mix 4) Antimicrobial preservatives 5) Flavors/colors |
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How do you choose an emulsifying agent?
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1) Must be compatible with other ingredients
2) Does not interfere with the stability or efficacy of the therapeutic agent 3) Must be stable over the shelf life of the product 4) Must be nontoxic (for route of administration) 5) Must possess little odor, taste, or color 6) Must promote emulsification (duh) 7) Must maintain stability of the emulsion |
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What is HLB? describe it.
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Hydrophillic lipophilic balance
HLB values are 1-20 based on chemical balance 20 = more hydrophobic 1 = more lipophilic |
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What HLB values are for w/o emulsions? o/w emulsions?
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HLB of 3-6 = w/o emulsion
HLB of 8-18 for o/w emulsion |
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What HLB does acacia have?
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HBL = 8, used a lot!
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How do you choose an emulsifying agent?
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HLB value of the emulsifier should be close to the HLB value of the oil phase.
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Can you mix emulsifying agents?
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Yes! They can be mixed in order to obtain the desired HLB.
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Know how to mix two emulsions with a specific HLB to get the HLB you want page 68
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Know how to mix two emulsions with a specific HLB to get the HLB you want page 68
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What is surface tension?
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The force per unit length which has to be applied to "pull" a liquid into the vapor phase
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What is interfacial tension?
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Force per unit length existing at the interface between two immiscible liquid phases
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What does CMC mean? What is the significance of this?
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Critical micellar concentration.
The concentration of the emulsifying agent should be slightly above the CMC |
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Know the surfactant and micelle drying on page 69
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Know the surfactant and micelle drying on page 69
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What is cohesion?
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Attraction between like molecules w-w or o-o
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What is adhesion?
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Attraction between unlike molecules w-o
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What must an emulsifying agent do in regards to adhesion and cohesion?
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An emulsifying agent must decrease the COHESIVE forces and increase the ADHESIVE forces
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What are the three emulsification theories?
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1) Surface-tension theory
2) Oriented-wedge theory 3) plastic or interfacial-film theory |
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What is the surface tension theory (emulsions)?
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Emulsifier decreases surface (interfacial) tension between the internal and external phases
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What is the oriented-wedge theory (emulsions)?
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Emulsifier is dissolved in the phase in which it is most soluble and forms a wedge between the two phases
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What is the plastic or interfacial film theory (emulsions)?
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Emulsifier surrounds the droplets of the internal phase and prevents contact and coalescence of the internal phase.
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Of the emulsification theories, which one results in a good emulsion?
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Some or all of the theories may occur at any one time in an emulsion!
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How can you detect the emulsion type? Describe them
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1) Dilution test - add a droplet of water, if it forms a drop its w/o, if it mixes easily its o/w
2) Conductivity test - does not conduct electricity = w/o. If it does conduct electricity its o/w. 3) Dye solubility test - if it changes color its o/w. If droplet of dye forms w/o. |
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Why should you use an emulsion?
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1) o/w emulsions for oral administration of oil. Water phase can be sweetened. Reduced droplet size of oil makes it more readily absorbable.
2) Topical preparations: Decreases irritation of the skin if it is in internal phase, patient acceptable. 3) Parenteral emulsions: Used for parenteral nutrition. Contains 10-20% oil phase, egg phosphatides as an emulsifying agent, and glycerin as a stabilizer. |
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What are the 4 methods of preparing an emulsion?
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1) Continental/dry gum method
2) English/wet gum method 3) Bottle method 4) Mechanical methods |
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Describe the continental/dry gum method of preparing an emulsion.
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emulsion nucleus = 4:2:1 oil:water:gum
1) Thoroughly mix the gum and the oil in a DRY porcelain mortar and pestle 2) Add water to the mixture all at once and emulsify in the motor and pestle 3) Add the other ingredients previously mixed in the emulsion nucleus 4) q.s. as needed |
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Describe the english/wet gum method of preparing an emulsion
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Emulsion nucleus = 4:2:1 oil:water:gum
1) Mix water and gum in a porcelain mortar and pestle 2) Add oil phase slowly in portions with thorough mixing after each addition 3) Add the other ingredients previously mixed to the emulsion nucleus 4) q.s. as needed |
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Describe the bottle method of preparing an emulsion
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1) Place the gum in the bottle and add the oil phase
2) Mix thoroughly by shaking the bottle 3) Add the water phase in small portions and shake the mixture well after each addition |
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Describe the mechanical methods of preparing an emulsion
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1) Blender
2) Homogenizer |
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Describe the degradation of an emulsion (4 steps)
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1) Creaminig - Happens in o/w emulsions, droplets float
Sedimentation - Happens in w/o, drops go to bottom 2) Aggregation - droplets stick together (not combining) 3) Coalescence - Droplets form larger droplets. May or may not be able to be remixed 4) Cracking/breaking - Two separate layers now! |
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What can happen to the stability of an emulsion regarding its two phases?
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Phase inversion. Switch from oil/water to water/oil or vice versa
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What are some causes of instability in emulsions?
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1) Improper preparation
2) Improper phase/volume ration. Dispersed phase needs to be 25-70% of the total volume. If its greater then 70% you have droplet crowding, <25% its less stable 3) Extreme temperatures 4) Extreme light 5) Aging 6) Microbial contamination 7) Addition of other ingredients (salts can interact with emulsifying agent, or acacia/alcohol) |
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What are some tests for emulsion stability?
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1) Visual examination
2) Photomicrography 2) Particle size distribution 4) Centrifugation (more g's it can take the more stable) 5) Temperature stress test |
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What are the two specialized emulsions? Describe them.
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1) Microemulsion
- May appear almost transparent due to small droplet size, prepared using microfluidizer, really expensive! 2) Water-in-oil-in-water (w/o/w emulsion - Water droplets dispersed in oil droplets, which are dispersed in water. - Used for sustained release - Water moves to outside of oil bubble to release drug |
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Look at comparison of solution and dispersed system on page 73!
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Look at comparison of solution and dispersed system on page 73!
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Aerosol power depends on what?
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The power of a compressed or liquified gas to expel the contents from the container.
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How do aerosols differ from other dosage forms?
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They difference in their dependence on the function of the container, its valve assembly, and the propellant for delivery of the medication in proper form.
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What are the components of an aerosol?
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1) Product concentrate (drug, solvent, etc)
2) Propellant - key to aerosol 3) Solvent 4) Container (coated or uncoated glass, metal (usually), or plastic) 5) Valve and actuator system |
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What are the parts of an aerosol container? May have to label these! Look at page 421 in book
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1) Actuator
2) Stem 3) Gasket 4) Spring 5) Housing 6) Mounting cup 7) Dip tube 8) Container |
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What dispersion systems can an aerosol contain?
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1) Solution (although technically not a dispersion system)
2) Suspension 3) Emulsion |
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The majority of aerosols have what kind of dispersion system?
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Suspension
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What are the intended applications for aerosols?
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1) Topical
2) Body cavities (ear, rectum, vagina) 3) Oral for effect on pulmonary airways or oral cavity (buccal or sublingual) |
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What determines particle size of the expelled substance?
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The size of the opening of the actuator and the amount and type of propellant.
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What are the advantages of an aerosol dosage forms?
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1) Lower chance of contamination
2) Protection of drug from the environment 3) Topical aerosols (dermal, vaginal, rectal) can be applied in a uniform, thin layer. Eliminates irritation (usually caused by fingers/applicator). Can be delivered as an expanding foam to ensure direct contact of the drug with rectal or vaginal mucosa. 4) dosages can be delivered accurately, effectively, and efficiently using metered valves (MDI) 5) More efficient due to less waste and messiness. |
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Describe the characteristics of a good propellant
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1) Vapor pressure = 10-15psig (25-30psia) at 70*F (21*C)
2) No physiological effects (nonirritating, toxic, no color, odor. 3) Chemically inert ( does not react with drug or parts of the container and valve assembly) 4) Nonflammable/explosive 5) Good solvent power 6) Practical costs |
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What is the propellant? Examples?
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Liquified gas or mixture of liquified gases
i.e. Chlorofluorocarbons (CFCs) Hydrocarbons (propane/isobutane) Fluorocarbons/fluoroalkanes (HFA) Nonliquified compressed gases i.e. Carbon dioxide, nitrogen, nitrous oxide Mechanical energy |
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What did the clean air act of 1990 do? Why?
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Regulations by the FDA and EPA prohibiting the use of chlorofluorocarbons (CFCs) in non essential products
CFC depletes the ozone layer. Required statement on packaging for aerosols containing CFCs |
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Describe Chlorofluorocarbon propellant
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CFCs, destroys ozone layer and will be removed from the market.
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Describe fluoroalkane propellants
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Only one type of fluoroalkane approved for use in pharmaceutics.
HFA 134a = 1, 1, 1, 2-tetrafluoroethane |
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Describe hydrocarbon propellants
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Highly flammable and can be harmful if inhaled
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Describe compressed gas propellants
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Will diminish in pressure as the product is used
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Describe mechanical energy propellants
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More difficult for pastiest to use
Approved in oct 7, 2011 New example: Combivent, respimale |
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How does a liquified gas propellant work?
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An equilibrium is established between liquified and vaporized propellant
The vaporized propellant exerts pressure on the surface of the liquid phase and forces it up through the dip tube and out of the orifice When the liquified propellant meets the air, it evaporates immediately and leaves the product as airborne liquid droplets or drug particles Equilibrium is reestablished every time a dose is delivered |
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What is the two-phase liquified gas propellant system?
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Has liquid phase and vapor phase
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What is the three-phase liquified gas propellant system?
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Has two immiscible liquid phases and a vapor phase
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Describe the compress gas propellant system.
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Has a compressed gas and liquid product concentrate (no liquified propellant in this one)
Pressure diminishes as the product is used (due to inverse volume-pressure relatiobnship) |
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What is cold filling?
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Used to fill aerosol containers.
Propellant and product concentrate are cooled to -34*C to -40*C and added before container is sealed. |
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Cold filling cannot be used with what?
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COLD FILLING CANNOT BE USED WITH AQUEOUS SYSTEMS.
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What is pressure filling?
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Propellant added through the valve stem after the container is sealed.
Less chance for moisture contamination! |
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Which type of filling of aerosols is most commonly used?
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Pressure filling
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What do they test for with filled containers?
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1) Leaks or weaknesses in the valve assembly or container
2) Valve discharge rate 3) Spray pattern 4) Particle size distribution 5) Accuracy and reproducibility of doses using metered valves 6) Pressure inside canister at room temperature |
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How can we measure particle size distribution of an aerosol?
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X-ray diffraction
Marple-miller impactor |
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What are the commercially available pharmaceutical aerosols? Give examples.
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1) Oral inhalations - antiasthmatics, antiinflammatory agents
2) Nasal inhalations - antiinflammatory agents Topical - Anesthetics, antifungal, antiseptics |
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What are inhalations and describe them.
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Drug administered by the oral respiratory route.
Local effect on bronchial tree Absorption from the lungs i.e. adasure (loxapine) |
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What is the maximum particle size for penetration for oral inhalations? List size for each area!
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1) Trachea - 60um
2) Terminal/respiratory bronchiole - 20um 3) Alveolar duct - 6um 4) Alveoli - 2um or less |
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What happens if the particles are too large for inhalations?
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Particles that are too large will impact on the back of the throat.
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WHat happens if the particles are too small for inhalations?
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Particles that are too small will be exhaled
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Why are lungs and ideal area for absorption?
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Large surface area
Highly vascularized Thin membrane for permeation |
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What are the disadvantages of using lungs for systemic absorption?
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1) proper education for administration
2) Pulmonary congestion. Acute or chronic 3) Cost |
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Powders for inhalation have a particle diameter of?
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1-6um
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Advantages of powder inhalers?
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1) Easier to use in aerosols
2) Fewer steps required for administration 3) Dose counter on most products 4) No propellant required (CFCs!) |
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What are the disadvantages of powder inhalers?
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1) Drug is "pulled" into the lungs as patient inhales
2) May be irritating to the throat and cause cough |
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First inhalations approved for systemic absorption?
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Exubera inhaled insulin
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In a nicotine inhaler where is most of the drug absorbed?
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In the mouth
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What is a nebulizer?
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Produces fine particles (0.5-5um) for inhalation therapy.
Drug solution is inhaled over a prolonged length of time i.e. 30 minutes |
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What is a vaporizer?
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Produces a fine mist of steam
Volatile medications can be added Kills mold and bacteria present in water tank Danger of scalding (especially in small children) |
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What is a humidifier?
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Provides a cool mist to the air
More expensive and noisier operation but uses less electricity than vaporizers May produce airborne mold, bacteria, lead, and organic gases. |
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What are the functions of the skin?
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1) Containment of body fluid and tissues
2) Protection from harmful external stimuli 3) Reception of external stimuli 4) Regulation of body temperature 5) Synthesis and metabolism 6) Disposal of biochemical waste (through secretions) |
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Examples of protection harmful external stimuli (skin)
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1) Microbial barrier
2) Chemical barrier 3) Radiation barrier 4) Thermal barrier 5) Electrical barrier |
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Examples of reception of external stimuli (skin)
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1) Tactile
2) Pain 3) Thermal |
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What is normal body temperature?
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98.6*F
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Describe the anatomy of the skin
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1) Stratum corneum - Top layer, if it passes this, usually its absorbed.
2) Epidermis 3) Dermis - where blood vessels are |
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What is the definition of an ointment?
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Semisolid preparation intended for external application to the skin or mucous membrane
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Ointments usually contain what?
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Medicinal substances.
Must match ointment base to drug being incorporated |
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Topical ointments are used for what?
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Local effect
- Surface activity - Effect within stratum corneum |
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Transdermal ointments are used for what?
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Systemic effect
- Activity requiring penetration into the dermis and epidermis. |
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What are the disadvantages of transdermal ointments?
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1) Difficulty measuring does. Usually use length (inches, syringe, metered-dose pump, or packet to help
2) Difficulty in maintaining contact with skin |
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What happens if a transdermal ointment acts like a topical ointment?
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Drug is not absorbed into blood stream and desired effect is not achieved
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How can a topical ointment act like a transdermal ointment? Examples?
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If patient uses medication too often or over a large area the drug can be absorbed systemically and can produce adverse effects.
i.e. corticosteroids, antibiotics, topical anesthetics |
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What was the drug being used for topical effect, but because of its high dose caused arrhythmias and an FDA ruling?
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5% lidocaine.
FDA ruling against pharmacy companies compounding high potency ointments |
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What are the characteristics of an ideal ointment base?
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1) Nonirritating to skin, some may be nonirritating on one area, but irritable to others (mucous membrane)
2) Easily removable 3) Nonstaining 4) Stable 5) non-pH-dependent 6) Compatible with a variety of drugs |
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What are the four types of ointment bases?
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Hydrocarbons (or oleaginous)
Absorption (or absorbent) Water-removable (o/w emulsion type) Water-soluble |
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Describe hydrocarbon ointment base
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a.k.a. oleaginous
i.e. White ointment USP Emollient (puts moisture into skin) Occlusive (protects area) Nonwater-washable Hydrophobic Greasy |
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Describe absorption ointment bases
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a.k.a. absorbent
Anhydrous type i.e. Hydrophilic petrolatum USP w/o emulsion type i.e. Cold cream USP emollient Occlusive Absorbs water Greasy |
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Describe water-removable ointment bases
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o/w emulsion type
i.e. hydrophilic ointment USP (velvachol) water-washable nongreasy Can be diluted with water nonocclusive |
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Describe water-soluble ointment bases
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i.e. polyethylene glycol ointment NF
usually anhydrous Water-soluble and washable nongreasy nonocclusive lipid-free Least common, most irritating! Bactroban |
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What factors should you consider during the selection of ointment base?
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1) Desired release rate of the drug from the ointment base
2) Site of drug action (local vs systemic) 3) Short-term and long-term stability of the drug in the base 4) Influence of the drug on the consistency and other properties of the base 5) Patient factors (dry vs wet skin) |
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How is the release rate of the drug changed with the selection of ointment base?
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If drug is dissolved in the base, you get a slower release rate.
If the drug is suspended in base, you get a faster release rate. |
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What bases do ointments use? What is it preferred for? Why?
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Hydrocarbon or anhydrous absorption bases
- Prefered for dry and scaly lesions - Less drying then creams - More potent in general |
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What bases do creams use? What is it preferred for? Why?
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w/o or o/w bases.
- Used on oozing lesions or in chafed areas where the occlusive effect of ointments may cause wasting and folliculitis - Patient prefer creams over ointments because they are easier to spread and easier to remove. |
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What are the ways to prepare an ointment?
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1) Incorporation
2) Fusion 3) Mechanical |
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What is the incorporation method for preparing an ointment?
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1) Ointment slab/pill tile - Used for ointment preparations requiring only small amounts of solid or liquid
2) Mortar and pestle - Can be used for any ointment preparation, messy clean up. 3) Plastic bag - Should not be used when solids or reactive liquids are incorporated |
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What is the fusion method for preparing an ointment?
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- Stir until congealed for ointments containing insoluble solids
- Heat and mix all ingredients while stirring - Melt material with highest melting point first - For emulsion ointment bases - Heat oil and water phases to 70-75*C unless otherwise specified. - Add water to oil phase slowly |
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Describe the mechanical method for preparing an ointment.
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Electronic motar and pestle (EMP)
- Ointment is mixed directly in the jar - Mainly used for large quantities Ointment mills - Metal or ceramic rollers finish ointment by breaking down particle size. |
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What are lotions?
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Liquid preparations intended for external application
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Describe a lotion suspension.
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Suspension containing finely powdered substances that are insoluble.
- Intended to dry on the skin, leaving behind a thin film of their medical components. |
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Describe a lotion emulsion.
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Emulsions containing immiscible liquids
- Generally absorbed into the skin |
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Advantages of lotions?
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- Fluidity permits rapid and uniform application over a wide surface area
- Package in bottles - Shake well |
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Describe pastes.
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- Generally contain a larger percentage of solid material than ointments
- Levigating agent is usually a portion of the base - Thicker and stiffer than ointments - More absorptive and less greasy than ointments - Often used to absorb serous secretions - Packaged in jars |
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Describe plasters
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Solid or semisolid adhesive masses spread upon a suitable backing material (paper, cloth, plastic)
Intended for external application to provide prolonged contact at that site. |
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Describe glycerogelatins
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- Plastic masses consisting of glycerin and gelatin intended for topical application
- Melted prior to application and cooled to slightly above body temperature - Applied with a brush and allowed to harden - Covered with a bandage and remain in place for 6 weeks. |
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Describe how to package an ointment tube
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1) Place ointment in a narrow "glob" along the center of a large weighing paper
2) Roll paper up a little smaller than the end opening of the tube 3) Remove cap from tube 4) Insert paper with ointment 5) Replace cap on the tube 6) Press down end opening of the tube and quickly remove paper with one swoop 7) Tap on the cap end to minimize air pockets 8) seal end of the tube |
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Describe how to package ointment jars
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1) Fill using a spatula by pressing small amounts of the ointment into the bottom of the jar against the side
2) minimize air pockets 3) Finish the top flat |
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Jars vs tubes, who will win!?
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- Tubes allow less exposure of the ointment to the atmosphere
- Tubes more convenient for patients - Jars are easier to fill and less expensive - Metal tubes dent (although plastic and laminate don't) - There is a "push up" jar, but its expensive |
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How should you store ointments?
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- Below 30*C
- Phase separation of creams - Leakage from container may occur - "yukky" |
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For the preservation of ointments, USP requires what?
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USP requires the absence of Pseudomonas Aeruginosa and Staphylococcus Aureus
CFU = colony forming unit. Also limits of 100cfu/mL or g for bacteria AND 10cfu/mL or g of yeast and mold |
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What are some preservatives used for ointments?
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Methylparaben, propylparaben, p-hydroxybenzoates, phenols, benzoic acid, sorbic acid, quaternary ammonium salts
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What practice is important for preserving ointments?
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Hygienic practices.
Make sure the patient knows to wash hands first so they don't contaminate the rest of the ointment. Some ointments encourage microbial growth while others discourage it! |
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What are the properties of pharmaceutically elegant ointment?
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- Proper packaging (no dents in tube, properly sealed, non-greasy)
- Uniform (color, appearance, consistency) - Non-gritty - Smooth |
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What does a counterirritant ointment do?
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Induces a mild irritation to disguise a more severe pain (menthol, capsaisan)
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What does a rubefacient ointment do?
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Induces a mild irritation with erythema, gives a feeling of warmth and possibly causes itching.
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What does an antiseptic ointment do?
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Kills microorganisms
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What does an anesthetic ointment do?
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Numbs the nerve endings
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What does an astringent ointment do?
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Causes protein precipitation, dries out the skin, stops bleeding.
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What does a protectant ointment do?
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Provides a physical barrier to the environment
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What does an emollient ointment do?
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Imparts moisture to the skin and softens it
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What does an anti-inflammatory ointment do?
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Decreases inflammation on the skin
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What does sunblock ointment do?
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Prevents UV rays from damaging the skin
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What does an antipruritic ointment do?
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Decreases itching
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What does a keratolytic ointment do?
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Promotes desquamation by loosening the keratin in the skin. Wort or callus remover.
DO NOT SELL TO DIABETIC PATIENTS |
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What are the application of ointments to mucosal membranes?
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- Ophthalmic - ointments must be sterile
- Rectal - Ointment tubes for rectal use have a special applicator tip which should be cleaned after use - Vaginal - Vaginal ointments and creams are applied using a special applicator or contraceptive creams can be placed on the diaphragm. |
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What are transdermal drug delivery systems designed for?
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Designed to support the passage of drug substances from the surface of the skin, through its various layers, and into the systemic circulation.
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What is percutaneous absorption?
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The absorption of substances from outside the skin to positions beneath the skin, including entrance into the blood stream
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What does transcellular penetration mean?
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Penetration through cells
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What does intercellular penetration mean?
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Penetration between cells
i.e. lecithin |
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What does transappendageal penetration mean?
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Penetration via hair follicles
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Look at the flow chart on page 90
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Look at the flow chart on page 90
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What are the 9 factors affecting percutaneous absorption?
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1) Drug concentration
2) Surface area of application 3) Physiochemical attraction of the drug to the skin rather than the vehicle 4) Ability of the vehicle to cover the skin and mix with the sebum 5) Ability of the vehicle to increase hydration of the skin 6) Rubbing the site of application 7) Thickness of the stratum corneum 8) Length of the time drug is in contact with the skin 9) Multiple applications |
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How can you enhance percutaneous absorption?
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Reduce the resistance of the stratum corneum by altering physiochemical properties.
by: 1) Alter hydration of stratum corneum 2) Effect a change in the structure of the lipids and lipoproteins in the intercellular channels through solvent action or denaturation 3) Aide in the transport of ionizable drugs |
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What is the new system that can enhance percutaneous absorption? (not widely used yet)
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ZP Patch transdermal technology
Adhesive patch with titanium screen supporting precision microinjections that penetrate the skin to reduce resistance of the stratum corneum - Can enhance drug delivery through skin - Creates advantage for peptide drugs and other macromolecules - Microprojections can be coated with drug for immediately delivery - ZP patch applicator is used to apply the patch to the skin |
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What are the two methods for evaluating percutaneous absorption?
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In vitro - transdermal cells
In viv - animal and human models |
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How do in vitro evaluations of percutaneous absorption work?
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Two transdermal cells with a membrane between them.
One side has drug, the other side has a receptor solution After a period of time you check if drug has crossed membrane into receptor solution. |
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Know the diffusion calculation on page 93!
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Know the diffusion calculation on page 93!
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When calculating DM/dt (change in amount of drug per unit time) What do we assume?
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Steady state - Change in concentration in the membrane over time is zero.
"Sink" conditions - As soon as the drug passes through the membrane it is removed. |
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What are the two types of transdermal dosing systems?
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1) The transdermal system controls the rate of drug delivery to the skin ("rate-controlling)
2) The skin controls the rate of drug absorption. |
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If skin controls the rate of drug absorption, what do we need to keep in mind>?
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Variation in the skin will affect the amount absorbed.
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What are the design features and objectives of rate-controlling transdermal drug delivery systems? (7)
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1) Deliver the drug at a controlled rate for absorption into the systemic circulation
2) The system should possess the proper physico-chemical characteristics to permit the ready release of the drug substance and facilitate its partition from the delivery system into the stratum corneum 3) The system should occlude the skin to ensure the one-way flux of the drug substance 4) The transdermal system should have a therapeutic advantage over other dosage forms and drug delivery systems 5) The system's adhesive, vehicle, and active agent should be nonirritating and nonsensitizing to the skin 6) The patch should adhere well to the patients skin and its physical size, appearance, and placement on the body should not be a deterrant to use. 7) The system should not permit the proliferation of skin bacteria beneath the occlusion |
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Most transdermal systems consists of what four components?
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1) Impermeable backing membrane that supports the system.
2) Polymer layer which serves as the drug reservoir 3) Microporous membrane filled with a nonpolar membrane 4) Adhesive film to make close contact with the skin and maintain the device in the desired position. |
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Describe the reservoir transdermal drug delivery systems.
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- Oldest type on the market
- Least complicated system - Drug reservoir is usually viscous liquid or semisolid - Overdose if cut or punctured. Membrane type |
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Describe the matrix transdermal drug delivery systems.
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- Second olest type on the market
- Drug matrix is usually flexible disk Monolith |
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Describe the drug-in-adhesive transdermal drug delivery system.
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- Newest type on the market
- Drug matrix is prepared using adhesive - Thinner than previous patches Monolithic type |
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Describe the multilaminate transdermal drug delivery system
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- Not yet on the market
- Potential for longer duration of action Membrane + monolithic |
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What are some patient instructions for transdermal drug delivery systems?
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- Remove the old patch before applying a new one
- Properly dispose of old patch - Share info carefully!! |
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When should a patch be removed?
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When it is no longer releasing the active ingredient at a constant rate (no matter how much drug is left!)
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Know the calculation for amount released at time t on page 96
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Know the calculation for amount released at time t on page 96
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Why do you need to do a drug release test?
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Used to ensure that drug is released from the patch at a constant and predictable rate
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What apparatuses are used for drug release test?
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Paddle over disk
Cylinder Reciprocating holder (flat or angled disk or cylinder) |
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How are drug release tests done?
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Define apparatus, dissolution medium, volume.
Temperature at 32 +- 0.5*C Sample intervals at certain times Analyze the drug See individual monograph |
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Acceptance levels, describe them
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Level 1: No system lies outside each of the stated ranges in individual monograph
Level 2: Average of 12 systems lies within each of the stated ranges. No individual value is outside the stated range by more than 10% of the average of the stated range. Level 3: Average of 24 systems lies within each of the stated ranges. Not more than 2 of the 24 systems are outside the stated ranges by more than 10% of the average stated range. None of the systems is outside the stated range by more than 20% of the average of the stated range. |
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How many numbers of systems to test at each acceptable level in a drug release test?
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Level 1 = 6
Level 2 = 6 Level 3 = 12 |
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What are some advantages of a transdermal drug delivery system?
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1) Avoids variable absorption and metabolism associated with oral therapy
2) Can be used when oral administration of the drug is unsuitable 3) Avoids the risks and inconveniences of parenteral therapy 4) Provides prolonged delivery of the drug over time and therefore improves patient compliance 5) Exdtends the activity of drugs having short half-lives 6) Provides capacity to terminate the drug effect by removal of the application system. 7) Provides ease of rapid identification of medication in case of emergency |
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What are some variables associated with absorption and metabolism of oral therapy?
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pH
Enzymatic activity Interactions with GI contents Avoids "first pass effect" |
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What are the disadvantages of transdermal delivery systems?
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1) Unsuitable for drugs that irritate or sensitize the skin
2) Only relatively potent drugs are suitable for transdermal delivery dfue to skin's impermeability 3) Technical difficulties associated with adhesion of the system to different skin types and under various environmental conditions. 4) Difficult and expensive to develop and manufacture. |
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Know the drug release profile picture on page 98
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Know the drug release profile picture on page 98
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Why is nicotine not good for transdermal systems?
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Addicts need a spike of nicotine to get a similar effect as smoking
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Why is nitroglycerin not good for transdermal systems?
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You need a nitrate free interval for it to have a good effect
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Transdermal patches are an ______________ for most drugs
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transdermal patches are an ADVANTAGE for most drugs
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First transdermal delivery system approved by the FDA was for?
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Motion sickness
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Drugs currently available as what?
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TOPICAL patch only!!
Not for transdermal absorption |
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Advantages of other dosage forms available for transdermal delivery
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Dosing flexibility
Adhesive problems |
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Disadvantages of other dosage forms currently available for transdermal delivery?
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Dose measurement
Contact time with skin Accidental contact |
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What is the patch that caused a safety announcent from the FDA on july 2010?
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Evamist, estradiol patch. Was rubbing off on babies
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Describe transmucosal drug delivery.
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Small adhesive patch applied to upper gum, usually for 24 hours
Cydot by 3M Faster onset and more rapid decline of plasma levels Excellent gingival tolerance and comfortable to patients Striant testosterone buccal system 30mg q12h |
