Influential Factors and Dosage Forms

Question 1

Why pharmaceutical dosage forms?

Answer 1

• Optimum drug effectiveness
  - rate-controlled drug action
  - site-specific drug action
  - liquid preparations of insoluble/unstable drugs
• maximum drug safety
  - safe/convenient/accurate delivery
  - concealing taste
• maximum drug reliability
  - protect drug from gastric acid
  - protect drug from atmospheric oxygen or humidity

Question 2

Influential Factors in Dosage Dorms Design

Answer 2

• molecular size and volume
• drug solubility and pH
• partition coefficient
• polymorphism
• stability
• pKa/dissociation constant
• particle side and dissolution rate
• membrane permeability

Question 3

Stokes-Einstein equation

• what is it?
• what does it mean?

Answer 3

D = RT / 6(pi)(n)r

D= diffusion coefficient cm2/sec
R= gas constant = 8.313 J/Kmol
T=Kelvin
n=solvent viscosity
r=solvated radius of diffusing solute

Therefore: drug diffusivity is inversely proportional to molecular volume, which is dependent on molecular weight and conformation

(Molecular size and volume

Question 4

Drug solubility and pH are affected by

Answer 4

• salt formation
• ester formation or introduction of polar functional groups
• cosolvent
• complex formation
• micronization

Question 5

Solubility of an acidic or basic drug is pH dependent and can be altered by this

Answer 5

Salt formation

Question 6

Polar functional groups include hydroxyl groups, amines, ammonium, aldehydes, and carboxylates

Answer 6

Ester formation or introduction of polar functional groups

Question 7

Solubility of phenobarbital in a mixture of water, alcohol, and glycerol is significantly higher compared to any of these single solvents

Answer 7

Cosolvent

Question 8

Solubility of a drug in a particular solvent may be increased by addition of a third substance which forms an intermolecular complex with the drug

Answer 8

Complex formation (cyclodextrin)

Question 9

Reduces drug particle size

Answer 9

Micronization

Question 10

-pH is one of the most important factors in the

Answer 10

Formulation process as it affects solubility and stability

Question 11

When two immiscible liquids contain a weak acid or base drug, a part of the drug. . .

Answer 11

Goes to the nonpolar phase and the remaining part of the drug goes to the aqueous layer
Like dissolves like: nonpolar species migrates to nonpolar layer—polar species migrate to polar aqueous layer

Partitioning

Question 12

A measure of drug’s distribution in a lipo-hydrophilic phase system an indicates its ability to penetrate biologic multiphase systems (equations)

Answer 12

Partition Coefficient

Octagon-water partition coefficient
(Drug Conc. In octanol)
P= ————————————-
(Drug Conc. Drug in water)

Ionizable Drug
(Drug Conc. In octanol or nonpolar phase)
P= —————————————————————
(1-alpha)(Drug Conc. In water or polar phase)
Alpha=degree of ionization

Question 13

Lipophilicity

Answer 13

LogP

Question 14

Partition Coefficient can be used in

Answer 14

• Drug extraction from plants or biologic fluids
• Transport/Permeation of Drug’s
• Drug absorption from dosage forms
• Antibiotics recovery from fermentation broth

Question 15

Three physical forms of drug systems

Answer 15

• Crystalline: poorly soluble
• Amorphous: more soluble
• Polymorphic: barbiturates, steroids, sulfonamides-exhibit polymorphism

Question 16

Physical forms of a drug can affects its _______ this the extent of its __________

Answer 16

Dissolution rate, absorption

Question 17

Changes in crystal characteristics can influence _____________ and _________ and thus can have important implications in dosage form

Answer 17

Bioavailability and stability

Question 18

Characteristics of pKa/Dissociation Constant

Answer 18

• dependent on the pH of the medium containing the drug
• affects drug absorption, biodistribution and elimination
• adjust vehicle pH to obtain optimum drug solubility and stability

Question 19

pKa PRACTICE PROBLEM

Answer 19

AND EQUATIONS!!!

PRACTICE THEM!!!!!

Question 20

States that drugs are absorbed by passive diffusion depending on the fraction on un-ionized form of the drug at the biological membrane

Answer 20

pH-partition theory

Question 21

Drug degree of optimization depends on both

Answer 21

Their pKa and the salutation pH

Question 22

Ionized drugs are more _____ and have minimal ________ ______ compared to unionized form of the drug

Answer 22

Hydrophilic, membrane transport

Question 23

The pKa of the molecule is the

Answer 23

pH at which there is a 50:50 mixture of conjugate acid-base forms

Question 24

Henderson-Hasselbalch equations for weak acids and weak bases

Answer 24

PRACTICE THEM

Question 25

The pH-partition theory does not hold true for most

Answer 25

Weak acids, which are well-aborted from the small intestine. This is also true for quaternary ammonium compounds (ionized at all pHs but readily aborted from the GI tract)

Question 26

The pH-partition theory does not take account:

Answer 26

• large epithelial surface areas of small intestine compensates for ionization effects
• long residence time in small intestine compensates for ionization effects
• charged drugs (quaternary ammonium compounds, tetracyclines) may interact with opposite charged ions resulting in neutral species-absorbable
• some drugs are adsorbed via active pathways and more
• drug absorption is affected by lipid solubility (thiopentone is more lipid soluble than barbitone and better absorbed)