Solubility studies and improvement techniques MCQs With Answer

Introduction: This set of MCQs on solubility studies and improvement techniques is tailored for M.Pharm students preparing for product development and technology transfer exams. The questions probe fundamental concepts such as intrinsic solubility, pH-solubility profiles, Noyes–Whitney dissolution theory, and the effect of polymorphism, particle size and crystallinity on solubility. They also cover practical enhancement strategies: salt formation, co-solvents, surfactants, solid dispersions, cyclodextrin complexation, nanocrystals, hot-melt extrusion, and SEDDS. Each question is designed to test both theoretical understanding and its application in formulation design and scale-up, helping students build competence in selecting and optimizing approaches for poorly soluble drug candidates.

Q1. Which equation quantitatively describes the dissolution rate of a solid drug particle under diffusion-controlled conditions?

• Nernst–Planck equation
• Noyes–Whitney equation
• Arrhenius equation
• Henderson–Hasselbalch equation

Correct Answer: Noyes–Whitney equation

Q2. The Ostwald–Freundlich equation explains the solubility increase of small particles due to which phenomenon?

• Increased crystalline lattice energy
• Surface curvature leading to higher vapor pressure
• Enhanced hydrogen bonding with water
• pH-dependent ionization

Correct Answer: Surface curvature leading to higher vapor pressure

Q3. Which of the following techniques primarily improves apparent solubility by creating a molecularly dispersed amorphous phase of the drug in a polymer?

• Micronization
• Salt formation
• Solid dispersion by spray drying
• Cyclodextrin complexation

Correct Answer: Solid dispersion by spray drying

Q4. When selecting a salt form to improve aqueous solubility, which property of the counterion is most critical?

• Its molecular weight
• Its pKa relative to the drug
• Its optical rotation
• Its melting point

Correct Answer: Its pKa relative to the drug

Q5. Which statement best describes “intrinsic solubility” of a drug?

• Solubility of the drug in presence of surfactant above CMC
• Solubility of the non-ionized form of a drug in a given solvent
• Solubility measured at the drug’s pKa
• Solubility in biorelevant media only

Correct Answer: Solubility of the non-ionized form of a drug in a given solvent

Q6. Which technique reduces particle size to the nanometer range by high-energy wet milling to increase dissolution rate and apparent solubility?

• Hot-melt extrusion
• Jet milling
• Wet media milling to form nanocrystals
• Spray congealing

Correct Answer: Wet media milling to form nanocrystals

Q7. Cyclodextrin complexation primarily enhances solubility by which mechanism?

• Forming covalent bonds with drug molecules
• Encapsulating the hydrophobic moiety inside its hydrophobic cavity
• Altering drug pKa to increase ionization
• Reducing particle size through attrition

Correct Answer: Encapsulating the hydrophobic moiety inside its hydrophobic cavity

Q8. For a weakly basic drug with pKa 8.5, at which pH would you expect maximum aqueous solubility assuming ionization drives solubility?

• pH 2.0
• pH 7.0
• pH 9.5
• pH 12.0

Correct Answer: pH 2.0

Q9. Which parameter is NOT directly improved by particle size reduction?

• Dissolution rate
• Saturation solubility through Ostwald effect (for nanoscale)
• Permeability across a lipophilic membrane
• Surface area to volume ratio

Correct Answer: Permeability across a lipophilic membrane

Q10. Self-emulsifying drug delivery systems (SEDDS) improve oral absorption of lipophilic drugs primarily by:

• Forming microemulsions in the gastrointestinal fluids that improve drug dispersion and lymphatic uptake
• Crystallizing the drug into a more soluble polymorph
• Changing drug chemical structure to a more polar analog
• Increasing stomach pH to enhance dissolution

Correct Answer: Forming microemulsions in the gastrointestinal fluids that improve drug dispersion and lymphatic uptake

Q11. Which analytical technique is most appropriate for detecting residual crystallinity in an ostensibly amorphous solid dispersion?

• Dynamic light scattering (DLS)
• X-ray powder diffraction (XRPD)
• High-performance liquid chromatography (HPLC)
• Ultraviolet-visible spectroscopy

Correct Answer: X-ray powder diffraction (XRPD)

Q12. Hydrotropy enhances solubility by:

• Formation of micelles above a critical micelle concentration
• Increasing thermodynamic activity of water via chaotropic co-solutes that interact with solute molecules
• Complexation with cyclodextrin
• Changing drug crystallinity via milling

Correct Answer: Increasing thermodynamic activity of water via chaotropic co-solutes that interact with solute molecules

Q13. Which of the following is a disadvantage of amorphous formulations compared with crystalline forms?

• Lower intrinsic solubility
• Increased physical instability and tendency to recrystallize
• Poorer dissolution rate
• Impossible to manufacture by spray drying

Correct Answer: Increased physical instability and tendency to recrystallize

Q14. During technology transfer of a solubility-enhanced formulation, which critical quality attribute is most important to monitor to ensure consistent dissolution performance?

• Particle size distribution and polymorphic form
• Color of the final blend
• Optical rotation
• Manufacturer’s logo on the container

Correct Answer: Particle size distribution and polymorphic form

Q15. Which solubility enhancement method would be least appropriate for a drug that is chemically unstable in aqueous solution?

• Cyclodextrin complexation
• Hydrophobic lipid-based formulation (SLN or SEDDS)
• Aqueous co-solvent system for immediate dissolution testing
• Spray-dried amorphous solid dispersion with polymer

Correct Answer: Aqueous co-solvent system for immediate dissolution testing

Q16. The Biopharmaceutics Classification System (BCS) classifies drugs with low solubility and high permeability as which class, and what is the main formulation challenge?

• Class I; rapid dissolution is not required
• Class II; dissolution rate-limited absorption requiring solubility/dissolution enhancement
• Class III; permeability enhancement required
• Class IV; only pH modification required

Correct Answer: Class II; dissolution rate-limited absorption requiring solubility/dissolution enhancement

Q17. In a pH-solubility profile for a weak acid, the pHmax is defined as:

• The pH where intrinsic solubility equals apparent solubility of the ionized form
• The pH of maximum chemical stability
• The pH at which the drug completely precipitates
• The pH where the drug has maximum log P

Correct Answer: The pH where intrinsic solubility equals apparent solubility of the ionized form

Q18. Which scale-up technology is particularly suited for continuous manufacturing of polymeric amorphous solid dispersions with good control over residence time and mixing?

• Batch solvent evaporation in rotary evaporator
• Hot-melt extrusion
• Small-scale spray drying only
• Manual tumble blending

Correct Answer: Hot-melt extrusion

Q19. Which of the following enhances solubility by increasing solvent polarity and reducing cohesive forces among solvent molecules?

• Use of nonpolar oils
• Addition of water-miscible co-solvents like PEG or ethanol
• Use of liposomes
• Salt crystallization

Correct Answer: Addition of water-miscible co-solvents like PEG or ethanol

Q20. The Ostwald ripening phenomenon in nanoparticle suspensions leads to:

• Uniform reduction of particle size over time
• Growth of larger particles at the expense of smaller ones, reducing stability
• Immediate chemical degradation of the drug
• Spontaneous amorphization of crystals

Correct Answer: Growth of larger particles at the expense of smaller ones, reducing stability

Download