KAPS Drug Formulation and Development 3 — Questions and Answers
Question 1: Which preformulation study measures the intrinsic rate of drug dissolution independent of particle size effects?
- Powder dissolution test
- Intrinsic dissolution rate (IDR) using a rotating disk (Correct answer)
- USP Apparatus II paddle method
- Dynamic light scattering
Correct answer: Intrinsic dissolution rate (IDR) using a rotating disk
The intrinsic dissolution rate uses a compressed disk of pure drug at constant surface area, isolating the drug's inherent dissolution properties from particle size effects.
Question 2: In designing a transdermal drug delivery system, which property of the drug is MOST critical for passive permeation through skin?
- High molecular weight (>500 Da)
- Moderate lipophilicity (LogP 1–3) (Correct answer)
- High water solubility (>10 mg/mL)
- Ionic character at physiological pH
Correct answer: Moderate lipophilicity (LogP 1–3)
Optimal transdermal permeation requires moderate lipophilicity (LogP 1–3) to partition into the lipid-rich stratum corneum while retaining enough aqueous solubility to partition into deeper aqueous layers.
Question 3: Which test is performed during tablet development to assess the ability of a tablet to withstand mechanical stress during manufacturing and shipping?
- Disintegration test
- Friability test (Correct answer)
- Hardness test only
- Dissolution test
Correct answer: Friability test
The friability test tumbles tablets in a drum and measures % weight loss, evaluating resistance to abrasion and chipping during handling.
Question 4: A drug substance exhibits polymorphism. Which polymorph is PREFERRED for oral solid dosage form development from a thermodynamic stability standpoint?
- The metastable polymorph with highest solubility
- The most thermodynamically stable polymorph (Correct answer)
- The amorphous form
- The hydrate with highest water content
Correct answer: The most thermodynamically stable polymorph
The most thermodynamically stable polymorph is preferred because it is least likely to convert to another form during storage, ensuring consistent dissolution and bioavailability.
Question 5: Which process converts a drug-polymer solution into a porous solid matrix by sublimation of the frozen solvent under vacuum?
- Spray drying
- Fluid bed granulation
- Lyophilization (freeze-drying) (Correct answer)
- Rotary evaporation
Correct answer: Lyophilization (freeze-drying)
Lyophilization freezes the solution and then removes the solvent by sublimation under vacuum, producing a porous cake ideal for heat-sensitive biologics.
Question 6: During stability testing per ICH Q1A(R2), what are the storage conditions for long-term stability testing of a drug product intended for storage in a refrigerator (2–8°C)?
- 25°C/60% RH
- 30°C/65% RH
- 5°C ± 3°C (Correct answer)
- 40°C/75% RH
Correct answer: 5°C ± 3°C
ICH Q1A(R2) specifies 5°C ± 3°C for long-term stability testing of refrigerated drug products.
Question 7: Which in vitro dissolution apparatus is MOST appropriate for testing soft gelatin capsules and suppositories due to minimal mechanical agitation?
- USP Apparatus I (basket)
- USP Apparatus II (paddle) (Correct answer)
- USP Apparatus III (reciprocating cylinder)
- USP Apparatus IV (flow-through cell)
Correct answer: USP Apparatus II (paddle)
USP Apparatus II (paddle) is recommended for soft gelatin capsules and suppositories, with sinker devices used to prevent floating of the dosage form.
KAPS Drug Formulation and Development 3
Which preformulation study measures the intrinsic rate of drug dissolution independent of particle size effects?