1.2 Influential Factors In Pharmaceutical Dosage Forms Objectives

Question 1

What are the 3-pharmaceutical dosage forms?

Answer 1

1. Optimum drug effectiveness
   2.Max drug safety
2. Max drug reliability

Question 2

4 Components of rational drug design

Answer 2

1. Drug
2. Disease
3. Disease site
4. Delivery system

Question 3

Why are pharmaceutical dosages important?

Answer 3

1. Safety & accurate delivery of the drug
2. Coated tablet
   - protect drug from atmospheric oxygen or humidity, & eliminate taste
3. Enteric-coated tablet
   - Protect from gastric acid (so it gets delivered tot he correct site rather than absorbed in the stomach)
4. Capsules, coated tabs, flavored syrup
   - Conceal bitter taste and odor
5. Suspensions
   - liquid form of insoluble or unstable drug in desired vehicle (not too stable in a liquid form for long so we constitute it when needed because they have short life as a liquid form)
6. Controlled release tab, caps, & sus
   - Provide controlled-rate of drug in the body
7. Rectal or vaginal suppositories
   - site-specific drug delivery

Question 4

What are the influential factors in dosage form design?

Answer 4

1. Molecular size & volume
   2.. Drug solubility & pH
2. Partition coefficient
3. Polymorphisms
4. Stability
5. pKa/Dissociation constant
6. Particle size & dissolution rate
7. Membrane permeability

Question 5

Molecular size & volume

Answer 5

1. Drug diffusion is inversely proportional to molecular volume
2. MV is dependent on MW & conformation
3. D = RT/6(pi)nr
   - D = diffusion coefficient (cm^2/s)
   - R = gas constant = 8.313 (J/Kmol)
   - T = Temp (K)
   - n = solvent viscosity
   - r = solvated radius of diffusion solvent

Question 6

Drug solubility & pH

Answer 6

pH affect solubility & stability (it depends on the location of the drug and the drug pH)

Question 7

Partition coefficient

Answer 7

1. Measures the drugs distribution in a lipophilic-hydrophilic system & ability to penetrate biologic system
2. P = drug con. in octanol/drug con. in water
3. Log P = logarithm of partition coefficient
   - measured by lipophilicity
   - used for drug extraction from plants/biologic fluid
   - tranpsort/permeation of drug
   - drug absorption from dosage form

Question 8

Polymorphisms

Answer 8

1. Crystalline: poorly soluble
2. Amorphous: more soluble
3. Polymorphic: exhibits both crystalline & amorphous
   *Physical forms affects dissolution rate & absorption

Question 9

pKa/dissociation constant

Answer 9

1. pKa = pH + log HA/A-
2. pKa = pH + log BH+/B

Question 10

What is pH-partition theory

Answer 10

• Drugs are absorbed via passive diffusion depending on the fraction of un-ionized drug at the biological membrane
• Ionization is dependent on pKa (acid=base) & pH
• Ionized drugs are harder to transport through the membrane compared to un-ionized drugs
• Stomach pH = 2, small intestine pH= 7.4

Question 11

Limitations on pH-partition theory

Answer 11

• does not account for compensation of high SA in SI
• doesn’t account for long residence time in SI compensating for ionization effects
• does not account for interactions of charged drugs making an absorbable neutral species
• does not account for drug absorption thru active pathways
• does not account for lipid solubility affecting drug absorption (lipophilic drugs are more easily absorbed)