lecture 1

Question 1

solution

Answer 1

homogeneous molecular dispersion

Question 2

emulsion

Answer 2

oil in water or water in oil

Question 3

suspension

Answer 3

solid in water or oil

Question 4

advantages of solution dosage forms

Answer 4

-homogeneous: no problem of content uniformity
-easy to manufacture
-good bioavailability

Question 5

components of solution dosage forms

Answer 5

-active ingredient
-solvent
-buffering agent
-preservative
-antioxidant, chelating agent
-flavor and sweetener

Question 6

solvent?

Answer 6

-water, vegetable oil (for long acting parenteral)
-co solvents (ethanol, glycerin, propylene glycol)

Question 7

T/F the buffer principle is when a solution of a strong acid and a salt of it conjugate base

Answer 7

false it is a weak acid

Question 8

weak acid removes

Answer 8

added base (OH-)
HA + OH- <——> H2O + A-

Question 9

salt removes

Answer 9

added acid (H+)
A- + H3O+ <——–> HA H2O

Question 10

handersen-hasselbalch equation

Answer 10

pH= pKa + log ([A-]/[HA])

Question 11

buffering capacity

Answer 11

-ability of a buffer to resist a change in pH due to added OH- or H+
-B= (change of acid or base added)/ (change of pH)
-max when pH= pKa

Question 12

van slyke equation

Answer 12

b= 2.3C (Ka[H3O+])/(Ka + [H3O+])^2

Question 13

what are the two common pharmaceutical buffers

Answer 13

citrate buffers and phosphate buffers

Question 14

what is the purpose of antimicrobial preservatives

Answer 14

-protect patient from pathogens
-maintain potency and stability of dosage forms

Question 15

what are the mechanism of action of antimicrobial preservatives

Answer 15

-preservatives adsorb to the bacterial membrane and disrupt the membrane. The membrane is lipophilic and has a net negative surface charge
-adsorption due to lipid solubility (alcohols, acids, esters)
-adsorption due to electrostatic attraction (quaternary ammonium compounds)

Question 16

bacterial content allowed in ampules

Answer 16

Must be sterile, single dose, no preservative needed

Question 17

bacterial content allowed in multiple dose vials

Answer 17

Must be sterile, may contain up to 10 doses, need a preservative to kill microorganisms introduced during use.

Question 18

bacterial content allowed in ophthalmic solutions

Answer 18

Must be sterile, must contain a preservative if packaged in multiple dose container

Question 19

bacterial content allowed in oral liquids

Answer 19

Need not be sterile but should not contain pathogens. FDA limits the number of organisms (e.g., E. coli) to be less than 100 per mL. Need preservative for multiple dose packages.

Question 20

ideal preservatives

Answer 20

-Effective in low concentrations against a wide variety of
organisms
-Soluble in formulation
-Non-toxic
-Stable

Question 21

bacterial content allowed in oral solids

Answer 21

Less likely to carry bacteria than liquid forms. Pathogen contamination is still a concern
(e.g., Salmonella). Test raw materials and be sure that the manufacturing facility is clean.

Question 22

pharmaceutical preservatives in alcohol

Answer 22

-Ethanol: Requires greater than 15%, limited to oral products, may be lost due to volatility.
-Benzyl alcohol: Also has a local anesthetic action. Burning taste – not used orally. Water soluble, stable over wide pH range. Widely used in parenterals.
-Chlorobutanol: Campor-like odor and taste – not used orally. Used in parenterals and ophthalmics. Volatile, lost through rubber stoppers and plastic containers

Question 23

pharmaceutical presevatives acids

Answer 23

-Only active in unionized (lipid-soluble) form.
-Benzoic acid (pKa = 4.2): Used in oral products.
-Sorbic acid (pKa = 4.8): Used in oral products, excellent for molds and yeast

Question 24

pharmaceutical preservatives esters of p-hydroxybenzoic acid (parabens)

Answer 24

-Widely used orally. Not ionize but hydrolyze rapidly at pH values above 7. Anesthetize tongue.
-Most lipophilic ones (Propyl paraben and butyl paraben) are best against mold and yeast; less lipophilic ones (methyl paraben and ethyl paraben) are best against bacteria.
-Low solubility is a problem.
-Cause skin sensitization when used in dermatological products

Question 25

factors affecting preservative action

Answer 25

-pH: Only the unionized species of weak acids are effective as a preservative. Need to add more total weak acid when pH is above pKa in order to have effective concentration of unionized species.
-Complex formation: Only the uncomplexed (free) preservative is active.
-Adsorption by solids: Only the unadsorbed preservative is active.
-Chemical stability: Consider the shelf-life

Question 26

pharmaceutical preservatives quaternary ammonium compounds

Answer 26

-Benzalkonium chloride (Zephirin)
-Cetyltrimethylammonium chloride (Cepryn)
-Widely used in ophthalmics. Very water soluble and fast killing. Incompatibility issues due to positive charge

Question 27

antioxidants

Answer 27

-Drug substances are less stable in aqueous media than solid dosage forms.
*Acid-base reactions, acid or base catalysis, oxidation, or reduction may occur from ingredient-ingredient interactions or container-product interactions

Question 28

antioxidant oxidation

Answer 28

-Main degradation pathway of pharmaceuticals
◦ Vitamins, essential oils, fats, and oils
-Auto-oxidation (automatic reaction with oxygen without drastic external interference)
-Initiated by heat, light, peroxides, metals (copper or iron) à free radicals à react with oxygen à more free radicals.

Question 29

antioxidant free-radical scavengers

Answer 29

Retard, delay oxidation by rapidly reacting with free radicals
* Propyl, octyl, dodecyl esters of gallic acid
* Butylated hydroxyanisole (BHA); Butylated hydroxytoluene (BHT)
* Tocopherols; Vitamin E

Question 30

antioxidants reducing agents

Answer 30

Have lower redox potentials than drug; more readily oxidized.
* Sodium bisulfite: 2NaHSO3 + O2 à 2NaHSO 4
* Ascorbic acid
* Thiols

Question 30

antioxidants chelating agents

Answer 30

-Antioxidant synergists
-Little antioxidant effect themselves
-Remove trace metals
* Citric acid; EDTA (Ethylenediaminetetraacetic acid)