Exam 1 - Basics

Question 1

Drug considerations in dosage form development:

Answer 1

• aqueous solubility, pKa, partition coefficient

* stability in solution

Question 2

Biopharmaceutical considerations in dosage form development:

Answer 2

• site of action – local? systemic?
• site, mechanism, and extent of absorption
• first pass metabolism?
• desired onset / duration of action

Question 3

Drug Product:

Answer 3

• dissolution, skin permeability
• storage stability, rate of degradation, storage restrictions
• packaging
• excipient compatibility
• patient compliance – taste, smell, mouth-feel, size, dosing frequency, “pharmaceutical elegance”

Question 4

“Manufacturability”:

Answer 4

• powder flow / powder & tablet compaction
• robust process
• cost of goods
• quality control/assurance

Question 5

Pharmaceutics is:

Answer 5

the science of pharmaceutical systems and application to the

design and manufacture of dosage forms

Question 6

Science of pharmaceutics incorporates:

Answer 6

• physical pharmaceutics (chemistry)
• biopharmaceutics
• dosage form design
• manufacturing scale – small, intermediate, large
• microbiology
• product performance/quality testing

Question 7

Drug:

Answer 7

Active Pharmaceutical Ingredient (API)

Question 8

Drug Product:

Answer 8

Dosage Form/Drug-Delivery System

Question 9

Goal of Dosage Form Design:

Answer 9

“Achieve a predictable, reproducible, therapeutic response in a dosage form that is amenable to large-scale manufacture” of predefined and controlled product quality.

Question 10

Important dosage form characteristics:

Answer 10

• stability (chemical/physical)
• uniformity of dosage units
• patient/prescriber acceptability
• appropriate packaging & labeling
• protection from microbial contamination

Question 11

Chemical properties of API:

Answer 11

solubility
particle size,
crystalline/amorphous form

Question 12

Dosage form/API is determined by:

Answer 12

• convenient and efficacious treatment of the disease
• most direct and effective route of delivery to the disease target
• minimize exposure at systemic targets unrelated to disease (minimize adverse effects)

Question 13

Factors guiding design of dosage forms:

Answer 13

1. Biopharmaceutics
2. Physicochemical characteristics of the
   active pharmaceutical ingredient (API)
3. Therapeutic intent – drug target / indication / patient satisfaction

Question 14

Biopharmaceutical Considerations for Dosage Form Design:

Answer 14

• Drug must be in solution
• Absorption generally via passive diffusion or carrier
mediated transport
• Passive diffusion rate – lipid solubility & degree of ionization
• Knowledge of transport carriers/mechanisms can guide drug design

Question 15

Routes of administration that allow drug to be absorbed directly into systemic circulation:

Answer 15

buccal 
respiratory
rectal
im
sc

Question 16

Routes of administration that allow drug to be directly delivered into systemic circulation:

Answer 16

Intravenous

Question 17

Barriers to systemic circulation when drug is administered orally:

Answer 17

GI transit time, absorption rate, portal circulation with potential first pass clearance

Question 18

Rectal administration:

Answer 18

• generally for local effects
• useful for drugs inactivated by the GI environment via oral route
• vomiting or unconscious patients
• avoids first pass
• inconvenient and absorption can be irregular

Question 19

Parenteral administration:

Answer 19

SC, IM, IV, intracardiac, intrathecal

Question 20

Particle size affects:

Answer 20

• dissolution rate
• absorption rate
• product content uniformity and stability

Question 21

Solubility affects passive absorption:

Answer 21

• low solubility – erratic or incomplete absorption
• pH
• can be enhanced by particle size reduction; complexation with hydrophilic polymers (e.g., cyclodextrins)
• can be diminished by excipients (lubricants) or manufacturing processes (over blending, over compaction)

Question 22

Noyes-Whitney Equation:

Answer 22

The process by which molecules of a solid in contact with a liquid leave the solid phase and form a one-phase, homogeneous, molecular mixture with the solvent.

Question 23

Biopharmaceutics Classification System (BCS):

Answer 23

Class I high solubility/high permeability propranolol; metoprolol

Class II low solubility/high permeability ketoprofen; carbamazepine

Class III high solubility/low permeability ranitidine; atenolol

Class IV low solubility/low permeability hydrochlorothiazide; furosemide

Question 24

Therapeutic Considerations in Dosage Form Design:

Answer 24

Delivery of API based on indication

Patient population