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24 Cards in this Set
- Front
- Back
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Why must a pharmaceutical buffer be composed of a weak acid and its salt?
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1. The weak acid removes added OH- (base)
HA + OH- <--> H2O +A- 2. the salt removes added H+ (Acid) A- + H3O+ <--> HA + H2O |
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Why are most pharmaceutical buffers based on acetic acid, cirtic acid, glycine, or phosphoric acid?
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The need to have a pKa close to the pH (needs to provide a useable pH range) and the need for a pharmacologically inert buffer.
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In designing a buffer, why is a weak acid with a pKa close to the desired pH selected?
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The maximum buffer capacity occurs with pH=pKa. Under these conditions the concentration of the weak acid, HA, equals the concentration of the salt, A-.
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What factors should be considered in selecting the pH?
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1. Use pH stability profile to select pH of maximum stability. This will give drug the longest shelf life. (Use pH stability profile- each drug has a unique profile.)
2. Minimize irritation (This is secondary. For example, if the pH was different in the eye- it would sting- but this would be transiet. STABILITY is the first priority.) |
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What are four ways to minimize irritation due to pH?
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A. Match pH of the body fluid (tears pH 7.4)
B. Minimize buffer capacity (competition between buffer capacity of body fluid and buffer capacity of drug- drugs with lower bc will be easier to overcome) C. Minimize volume administered D. Administer slowly (IV) |
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Sterility and preservative requirements of ampuls
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STERILE/NO PRESERVATIVE
-must be sterile, single dose, used only once, no preservative needed. |
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Sterility and preservative requirements of multiple dose vials
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STERILE/ PRESERVATIVE
- must be sterile, may contain up to 10 doses (exception for insulin)- need preservative to kill organisms introduced during use. |
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Sterility and preservative requirements of ophthalmics
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STERILE/ PRESERVATIVE
- must be sterile, must contain a preservative if packaged in multiple dose container- Preservative must kill QUICKLY- may be using every hour. The liquid may touch the eye and the container- contaminate the rest of the solution- (Note: Opthalmics are very innefficient- 5% of the drug stays in the eye long enough to do anything) |
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Sterility and preservative requirements of oral liquids
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NOT STERILE/ PRESERVATIVE
- need not be sterie but don't want pathogens. FDA limits the number or organisms to less than 100/mL. Need preservative fo multiple dose packages. If the number of organisms is very low the chance of a pathogen being there is also very low. |
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Sterility and preservative requirements of oral solids
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NOT STERILE/ NO PRESERVATIVE
- bacteria can't grow without water. May be carriers of pathogens. Salmonella is cheif caoncern. Test raw materials and clean manufacturing facility. No preservative. |
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What properties of the cell membrane are used to select compounds as preservatives?
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Preservatives adsorb to the bacterial membrane and disrupt the membrane. The membrane is lipophilic and has a net negative surface charge. There are two mechanisms:
1) Adsorption due to lipid solubility of the preservative- (alcohols, acids, esters) - this is the mechanism that most preservative act by- but often makes is more difficult to get into solution 2) Adsorption due to electrostatic attractions (quaternary ammonium compounds)- very water soluble |
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Be able to give an example of a pharmaceutical preservative which is an alcohol.
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a. Ethanol- if used as a preservative probably used as a cosolvent also- requires greater than 15%, limited to oral products; lost due to volatility.- not in eye drops/ IV- limited to oral
b. Benzyl alcohol- also has local anesthetic action, burning taste so not used orally, very water soluble, stable over wide pH range. Widely used i parentals c. Chlorobutanol-camphor-like odor and taste so it is not used orally, used in parentals and opthalmis, it is volatile and is lost through rubber stoppers and plastic containers |
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Understand why the published killing concentration of preservatives may be inadequate to preserve a solution, suspension, or emulsion dosage form.
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1. pH- only the unionized specie of weak acids is effective as a preservative. Thus, benzoic acid and sorbic acid lose activity when the pH increases. The pKa of benzoic acid is 4.2 and sorbic acid is 4.8. Need to add more total weak acid when pH is above pKa in order to have efective concentration of unionized specie. (Example- need more and more total benzoic acid- but only around 40 mg- constant of ionized)
2. Complex formation- only the uncomplexed (free) preservaive is active- tied to the polymer is not available to kill bug 3. Adsorption by solids- only unadsorbed preservative is active. Quaternary ammonium preservatives are bound by solids with negative surface charge. 4. Chemical stability- must consider the shelf-life in terms of both the drug and the preservative-PH very critical 5. Interaction with package (Ex. type of stopper or type of plastic bottle) |
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Know the components that may be required in a solution dosage form. Be able to give an example of each type.
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A. Solvent
B. Buffer C. Antioxidant D. Preservative E. Flavor and sweetener |
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Don't forget to look over the matching Study Questions- numbers 10-12.
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The Advantages of Solution Dosage Forms
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A. Homogeneous- no problems of content uniformity-this is unique- EVERY other dosage form is concerned with uniformity
B. Easy to manufacture Mixing tank--> Filter/ Polishing--> Fill C. Good bioavailability- introducing in a form able to pass GI tract--> in solution |
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Disadvantages of Solution Dosage Forms
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A. Taste
B. Not convienent |
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Definition of a Pharmaceutical Buffer
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A solution of a weak acid and its salt. (Weak bases and their salts are not used because they have a pharma action)
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Antimicrobial Preservation Problems
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1. Protect patient from pathogens
2. Maintain potency and stability of dosage form |
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Explain the challenge test- required by USP.
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1. Stimulates contamination during use.
2. Uses 5 organisms. a. Candida alicans- yeast b. Aspergillus niger- mold c. Escherichia coli d. Pseudomonas aeruginosa e. Staphococcus aureus f. may add another additional bug that they have a history of problems with 3. Require biocidal effect on non-spore formers (must KILL- count must go down to zero) and biostatic effect on spore formers (must show no growth- number must stay the same) |
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Ideal preservative:
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1. Effective in low concentrations against a widevariety of organisms
2. Soluble in formulation 3. Non-toxic- toxic to bug not to people 4. Stable |
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Be able to give an example of a pharmaceutical preservative which is an acid.
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Only active in unionized (lipid soluble) form- terrrible preservatives and pH 6-8.
a. Benzoic acid- pKa=4.2, used in oral products b. Sorbic acid- pKA=4.8, used in oral products, excellent for molds and yeast- food |
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Be able to give an example of a pharmaceutical preservative which is an ester.
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trade name=parabens- widely used orally, don't ionize but hydrolyze at pH above 7, anesthetize tongue, different esters (methyl, ethyl, propyl, and butyl paraben) have different bacterial spectrum. Most lipophilic (High MW- propyl paraben and butyl (as high as you can get while maintaining solubility) paraben) are best against old and yeast while less lipophilic (methyl paraben and ethyl paraben) are best against bacteria. The low aqueous solubility is a problem. Often most and less lipophilic used in pairs
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Be able to give an example of a pharmaceutical preservative which is a quat.
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Used in opthalmics- fast kill- very water soluble- have incompatibilities due to positive charge
a. Benzalkonium chloride (Zephirin) b. cetyltrimethylammonium chloride -mouthwash(Cepryn)- not oral- toxicity |
