Liquid Dosage Forms

Question 1

liquid dosage forms

Answer 1

-solution (homogenous molecular dispersion)
-emulsion (oil in water)
-suspension (solid in water or oil)

Question 2

Solution dosage form examples

Answer 2

-injectables
-nasal, opthalmic, otic, irrigation solutions
-enemas
-douches
-gargles
-juices

Question 3

Advantages of solution dosage forms

Answer 3

-homogenous (content uniformity)
-easy to manufacture
-good bioavailability

Question 4

Components of solution dosage forms

Answer 4

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

Question 5

Solvent

Answer 5

-water, oils (for long-acting)
-co solvent (ethanol, glycerin)

Question 6

Buffer principle

Answer 6

-solution of WEAK Acid and salt of CONjugate Base
-weak acid removes added base (OH-)

HA + OH- <–> H2O + A-

-salt removes added acid (H+)

A- + H3O+ <–>. HA + H2O

Question 7

Henderson Hasselbach

Answer 7

pH = pKa + log[A-/HA]

Question 8

Buffering capacity

Answer 8

-ability of a buffer to resist a change in pH due to added OH- or H+
-Van Slyke equation
-max when pH = pKa

Question 9

van slyke equation

Answer 9

B = (acid or base added/pH)

B = 2.3 C (Ka[H3O+]/((Ka+[H3O+])^2)
-C= total buffer concentration = [HA] + [A-]
-max when pH = pKa

Question 10

Common pharmaceutical buffers

Answer 10

-citric acid
-phosphoric acid
-also glycine and acetic acid

Question 11

Citrate buffers

Answer 11

-

Question 12

Phosphate buffers

Question 13

Selection of pH

Answer 13

-use pH that provides maximum stability for drug
-minimize irritation by adjusting pH to be same as pH of body fluid 7.4

Question 14

If you cannot match pH of body fluid,

Answer 14

-minimize buffering capacity
-minimize volume
-administer slowly

Question 15

Antimicrobial preservatives purpose

Answer 15

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

Question 16

Antimicrobial preservatives mechanism of action

Answer 16

-absorb and disrupt bacterial membrane
-via lipid solubility or electrostatic attraction

Question 17

bacterial membrane

Answer 17

-lipophillic
-negative surface charge

Question 18

Adsorption due to lipid solubility (antimicrobial preservatives)

Answer 18

-alcohols
-acids
-esters

Question 19

adsorption due to electrostatic attraction (antimicrobial preservatives)

Answer 19

quarternary ammonium compounds

Question 20

bacterial content allowed in dosage forms

Answer 20

-ampules (sterile)
-multiple dose vials (sterile)
-ophthalmic solutions (sterile)
-oral liquids
-oral solids

Question 21

Ampules

Answer 21

-must be sterile
-single dose
-no preservative needed

Question 22

Multiple dose vials

Answer 22

-must be sterile
-up to 10 doses
-NEED preservative to kill microorganisms

Question 23

Ophthalmic solutions

Answer 23

-must be sterile
-preservative if packaged as multiple dose use

Question 24

Oral liquids

Answer 24

-not sterile but no pathogens
-e. coli <100 per ml
-need preservative

Question 25

oral solids

Answer 25

-less likely to carry bacteria than liquids -test raw materials -clean manufacturing facility

Question 26

Ideal preservatives

Answer 26

-effective in low concentrations against a wide variety of organisms -soluble in formulation -non-toxic -stable

Question 27

Pharmaceutical preservatives

Answer 27

-alcohols -acids -esters -quarternary ammonium compounds

Question 28

Alcohols

Answer 28

-ethanol -benzyl alcohol -chlorobutanol

Question 29

ethanol

Answer 29

-requires more than 15% -limited to oral -may be lost due to volatility

Question 30

Benzyl alcohol

Answer 30

-local anesthetic action -burning taste--not used orally -water soluble -stable over wide pH range -used in parenterals

Question 31

Chlorobutanol

Answer 31

-campor-like odor and taste -not used orally -parenterals and ophtalmics -volatile, lost through rubber and plastic

Question 32

Acids

Answer 32

-only active in unionized (lipid-soluble) form -benzoic acid (oral)pka4.2 -sorbic acid (oral, good for mold and yeast) pka4.8

Question 33

Esters of P-hydroxybenzoic acid (parabens)

Answer 33

-widely used orally -not ionize but hydrolyze rapidly at pH values above 7 -anesthetize tongue -lipophilic ones good for mold and yeast -less lipophilic ones good for bacteria -low solubility is a problem -cause skin sensitizatin when used dermatologically

Question 34

Quarternary ammonium compounds

Answer 34

-benzalkonium chlorise (Zephirin) -Cetyltrimethylammonium chloride (Cepryn) -ophthalmics -water soluble -fast killing -incompatibility issues bc positive charge

Question 35

Factors affecting preservative action

Answer 35

-pH -complex formation -adsorption by solids -chemical stability

Question 36

pH

Answer 36

-only unionized species of weak acids are effective as a preservative -need to add more tatal weak acid when pH is above pKa in order to have effective concentration of unionized species

Question 37

complex formation

Answer 37

-only the uncomplexed (free) preservative is active

Question 38

Adsorption by solids

Answer 38

-only the unadsorbed preservative is active

Question 39

chemical stability

Answer 39

shelf-life

Question 40

Drug substances are less stable

Answer 40

-in aqueous media than solid dosage forms -acid-base reactions, catalysis, oxidation, reduction may occur from container-product interactions

Question 41

Oxidation

Answer 41

-main degradation pathway of pharmaceuticals -vitamins, fats -auto-oxidation -initiated by heat, light, peroxides, metals (cooper or ion) -free radicals --> react with oxygen --> more free radicals

Question 42

auto-oxidation

Answer 42

-automatic reaction with oxygen without drastic external interference

Question 43

Antioxidants

Answer 43

-free-radical scavengers -reducing agents -chelating agents

Question 44

free-radical scavengers

Answer 44

-delay oxidation by rapidly reacting with free radicals -gallic acid, BHT, BHA, Tocopherols, Vit E

Question 45

Reducing agents

Answer 45

-lower redox potentials than drug =. more readily oxidized -sodium bisulfate: 2NaHSO3 + O2 --> 2NaHSO4 -ascorbic acid -thiols

Question 46

chelating agents

Answer 46

-antioxidant synergists -little antioxidant effect themselves -remove trace metals -citric acid, EDTA

Question 47

MAthcing

Answer 47

matching

Question 48

Ka=

Answer 48

-log(pKa)

Question 49

[H3O+] =

Answer 49

-log(pH)