E 1 L 1 - Liquid

Question 1

Solution

Answer 1

Homogenous molecular dispersion

Question 2

Emulsion

Answer 2

Oil in water/water in oil

Question 3

Suspension

Answer 3

Solid in water or oil

Question 4

Examples of solution

Answer 4

Injectables
Nasal Solutions
Ophthalmic solutions
Otic solutions
Irrigation solutions
Enemas
Douches
Gargles
Mouthwashes
Juices

Question 5

Advantages of Solution dosage forms

Answer 5

**Homogenous - no problems of content uniformity
-Easy to manufacture
-Good Bioavailability

Question 6

Components of solution dosage forms

Answer 6

-Active drug (drug)
-Solvent (water/veg, oils, for Long-acting parenteral)
-Co-solvent (ethanol, glycerin, propylene glycol)
-Buffering agent
-Preservative
-Antioxidant, chelating agent
-Flavor and sweetener (sucrose, sorbitol)

Question 7

Buffer principle

Answer 7

A solution of a weak acid and a salt of its conjugate base
-Weak acid removes added base
-Salt removes added acid

Question 8

Common pharmaceutical buffers

Answer 8

Citric Acid
Glycine
Phosphoric acid

Question 9

Antimicrobial Preservatives purpose

Answer 9

-Protect patient from pathogens
-Maintain potency and stability of dosage forms

Question 10

Antimicrobial Preservatives mechanism of action

Answer 10

Preservatives adsorb 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 interaction (ex. quart. amines)

Question 11

Bacterial content allowed in: ampules

Answer 11

Must be sterile, single dose, no preservative needed

Question 12

Bacterial content allowed in: Multi dose vials

Answer 12

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

Question 13

Bacterial content allowed in: Ophthalmic solutions

Answer 13

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

Question 14

Bacterial content allowed in: Oral liquids

Answer 14

Need not to 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 15

Bacterial content allowed in: Oral Solids

Answer 15

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 16

Ideal Preservatives

Answer 16

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

Question 17

Pharm Preservatives: Alcohols

Answer 17

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 ophthalmic. Volatile, lost through rubber stoppers and plastic containers.

Question 18

Pharm Preservatives: Acids

Answer 18

-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 19

Pharm Preservatives: Esters of P-hydroxybenzoic acid (Parabens):

Answer 19

-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 20

Pharm Preservatives: Quaternary ammonium compunds:

Answer 20

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

Question 21

Factors affecting preservative action

Answer 21

-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 22

Antioxidants

Answer 22

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

Question 23

Antioxidants: Oxidation

Answer 23

-Oxidation: 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 ion-> free radicals react-> react with oxygen->more free radicals

Question 24

Antioxidants: Free-radical scavengers

Answer 24

Retard, delay oxidation by rapidly reaction with free radicals
-Propyl, octyl, dodecyl esters of gallic acid
-butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT)
-Tocopherols vitamin E

Question 25

Antioxidants: Reducing agents

Answer 25

-Have lower redox potentials than drug; more readily oxidized
-Sodium bisulfite: 2NaHSO3 +O2 -> 2NaHSO4
-Ascorbic acid
-Thiols

Question 26

Antioxidants: Chelating agents

Answer 26

-Antioxidant synergists
-Little antioxidant effect themselves
-Remove trace metals
(citric acid; EDTA)

Question 27

Chelating agents

Answer 27

EDTA and Citrate

Question 28

pH =

Answer 28

pka + log [A-]/[HA]

Question 29

How to find pKa from Ka

Answer 29

-log(ka)

Question 30

How to do pH when value added

Answer 30

subtract new value from acid, and add new value to conj. salt, and then do pH as normal

Question 31

c =

Answer 31

acid + salt