Solubility enhancement techniques MCQs With Answer

Solubility enhancement is crucial in pharmaceutics to improve dissolution rate, absorption, and oral bioavailability of poorly water‑soluble drugs. For B. Pharm students, mastering solubility enhancement techniques—such as particle size reduction, solid dispersions, amorphous conversion, salt formation, co‑crystals, pH adjustment, cosolvency, surfactants and micellar solubilization, cyclodextrin complexation, hydrotropy, nanosuspensions, nanoemulsions, and lipid-based systems (SEDDS/SMEDDS)—is essential for effective formulation development. Key concepts include Noyes‑Whitney dissolution, BCS classification, pKa–pH solubility profiles, wettability, and stability (recrystallization control). This knowledge enables rational selection of excipients, processing methods (hot‑melt extrusion, spray drying, lyophilization), and in vitro assessment (IDR, phase‑solubility). Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which statement best distinguishes solubility from dissolution rate?

• Solubility is the amount dissolved at equilibrium; dissolution rate is the speed of dissolving
• Solubility measures speed; dissolution rate measures equilibrium concentration
• Both describe the same property
• Dissolution rate depends only on temperature, not formulation

Correct Answer: Solubility is the amount dissolved at equilibrium; dissolution rate is the speed of dissolving

Q2. In the Noyes–Whitney/Nernst–Brunner equation, which variable is directly increased by micronization?

• Diffusion coefficient (D)
• Boundary layer thickness (h)
• Surface area of the solid (A)
• Saturation solubility (Cs)

Correct Answer: Surface area of the solid (A)

Q3. Which BCS class typically benefits most from solubility enhancement to improve oral absorption?

• Class I (high solubility, high permeability)
• Class II (low solubility, high permeability)
• Class III (high solubility, low permeability)
• Class IV (low solubility, low permeability)

Correct Answer: Class II (low solubility, high permeability)

Q4. For a weakly basic drug (pKa 8), solubility in GI fluids is maximized by which strategy?

• Formulating at intestinal pH 6.8 without modification
• Raising pH above 10 to deprotonate the base
• Lowering pH (acidic microenvironment) to increase ionization
• Adding hydrotropes only

Correct Answer: Lowering pH (acidic microenvironment) to increase ionization

Q5. Salt formation most reliably improves solubility when which condition is met?

• The drug is nonionizable and highly lipophilic
• The drug has an ionizable group and ΔpKa with counterion is ≥2–3
• The drug is already amorphous
• The drug is a strong acid paired with a strong acid

Correct Answer: The drug has an ionizable group and ΔpKa with counterion is ≥2–3

Q6. Which is a common carrier polymer to stabilize amorphous solid dispersions?

• Silicon dioxide only
• Povidone (PVP) or HPMC-AS
• Sodium chloride
• Calcium carbonate

Correct Answer: Povidone (PVP) or HPMC-AS

Q7. Compared to crystalline forms, amorphous drugs generally exhibit:

• Lower apparent solubility and higher stability
• Higher apparent solubility but lower physical stability
• The same solubility and stability
• Higher melting points and higher stability

Correct Answer: Higher apparent solubility but lower physical stability

Q8. Cyclodextrin complexation enhances solubility primarily by:

• Covalent binding to the drug
• Inclusion of hydrophobic moieties into a hydrophobic cavity
• Salt formation with the drug
• Raising the pH of the medium

Correct Answer: Inclusion of hydrophobic moieties into a hydrophobic cavity

Q9. An AL-type phase-solubility diagram (linear increase, slope < 1) typically indicates:

• Precipitation of the complex
• Formation of an insoluble 2:1 complex
• Formation of a soluble 1:1 inclusion complex
• No interaction between drug and ligand

Correct Answer: Formation of a soluble 1:1 inclusion complex

Q10. Which technique can produce molecularly dispersed amorphous solid dispersions?

• Hot-melt extrusion or spray drying
• Simple wet granulation with water only
• Direct compression without excipients
• Ball milling of API alone for 2 minutes

Correct Answer: Hot-melt extrusion or spray drying

Q11. Which surfactant property is critical for micellar solubilization?

• High melting point
• Critical micelle concentration (CMC) and micelle formation above CMC
• Zero HLB value
• Insolubility in water

Correct Answer: Critical micelle concentration (CMC) and micelle formation above CMC

Q12. Cosolvency increases solubility by:

• Decreasing drug ionization
• Increasing dielectric constant of the medium
• Decreasing polarity of the solvent mixture to better solvate the drug
• Forming covalent adducts with the drug

Correct Answer: Decreasing polarity of the solvent mixture to better solvate the drug

Q13. Hydrotropy typically involves:

• Use of low–molecular weight organic salts like sodium benzoate to stack around solutes
• Formation of metallic complexes
• Creation of covalent prodrugs
• Changing crystal habit from needle to plate

Correct Answer: Use of low–molecular weight organic salts like sodium benzoate to stack around solutes

Q14. A self-emulsifying drug delivery system (SEDDS) generally contains:

• Only water and buffer
• Oil, surfactant, and co-surfactant/co-solvent
• API and polymer only
• Only cyclodextrin and API

Correct Answer: Oil, surfactant, and co-surfactant/co-solvent

Q15. Which statement about nanosuspensions (drug nanocrystals) is TRUE?

• They require high oil content to dissolve drug
• They are pure drug particles in the nanometer range stabilized by surfactants
• They cannot improve dissolution rate
• They always increase chemical stability

Correct Answer: They are pure drug particles in the nanometer range stabilized by surfactants

Q16. Pharmaceutical cocrystals differ from salts because cocrystals:

• Involve proton transfer to form ionic species
• Use non-ionizable coformers with neutral API via hydrogen bonding
• Are always less soluble than the API
• Cannot alter dissolution rate

Correct Answer: Use non-ionizable coformers with neutral API via hydrogen bonding

Q17. A eutectic mixture of API with a carrier can enhance dissolution primarily by:

• Increasing particle size
• Lowering the melting point and creating fine dispersions on solidification
• Forming ionic complexes
• Converting API to a hydrate

Correct Answer: Lowering the melting point and creating fine dispersions on solidification

Q18. Supercritical CO₂ processing (e.g., SAS/RESS) can enhance solubility by:

• Producing large coarse crystals
• Generating porous, small particles with increased surface area and reduced crystallinity
• Increasing moisture content
• Forming covalent prodrugs

Correct Answer: Generating porous, small particles with increased surface area and reduced crystallinity

Q19. Which counterion is commonly selected to form a more soluble salt of a weakly basic API?

• Hydrochloride or mesylate
• Sodium
• Calcium
• Magnesium stearate

Correct Answer: Hydrochloride or mesylate

Q20. Wetting agents enhance dissolution mainly by:

• Increasing crystal hardness
• Reducing contact angle and improving penetration of dissolution medium
• Raising melting point
• Forming cocrystals

Correct Answer: Reducing contact angle and improving penetration of dissolution medium

Q21. Hot-melt extrusion improves solubility by:

• Converting API to a stable hydrate
• Dispersing API at molecular level in polymer, often forming amorphous solid dispersions
• Increasing crystal size
• Removing all excipients

Correct Answer: Dispersing API at molecular level in polymer, often forming amorphous solid dispersions

Q22. Which statement about lyophilization (freeze-drying) in solubility enhancement is correct?

• It cannot affect dissolution behavior
• It can create highly porous, rapidly wetting solids and stabilize amorphous forms
• It always crystallizes the API
• It replaces the need for surfactants

Correct Answer: It can create highly porous, rapidly wetting solids and stabilize amorphous forms

Q23. For a weak acid (pKa 4), which statement about pH–solubility is correct?

• Solubility increases as pH decreases below pKa
• Solubility increases as pH rises above pKa (ionization)
• pH has no effect on solubility
• Maximum solubility occurs at pH = pKa for all drugs

Correct Answer: Solubility increases as pH rises above pKa (ionization)

Q24. Intrinsic dissolution rate (IDR) testing is useful primarily to:

• Measure dissolution with changing surface area
• Rank forms (salts/polymorphs) at constant surface area
• Assess permeability across membranes
• Determine partition coefficient

Correct Answer: Rank forms (salts/polymorphs) at constant surface area

Q25. Regarding polymorphism and solubility, which is generally TRUE?

• The most stable polymorph has the highest solubility
• Metastable forms often have higher solubility but may convert to stable forms
• All polymorphs have identical solubility
• Polymorph selection does not affect dissolution

Correct Answer: Metastable forms often have higher solubility but may convert to stable forms

Q26. Mesoporous silica improves apparent solubility primarily by:

• Forming salts with the API
• Confining drug in pores to inhibit crystallization and increase surface area
• Acting as a hydrotrope
• Changing GI pH

Correct Answer: Confining drug in pores to inhibit crystallization and increase surface area

Q27. For o/w emulsions or microemulsions, surfactants with which HLB range are typically preferred?

• HLB 1–4
• HLB 4–6
• HLB 8–18
• HLB 20–30 only

Correct Answer: HLB 8–18

Q28. In nanosuspension stability, a zeta potential with magnitude ≥ about 30 mV generally indicates:

• Poor electrostatic stabilization
• Good electrostatic stabilization against aggregation
• No impact on stability
• Guaranteed chemical stability

Correct Answer: Good electrostatic stabilization against aggregation

Q29. Which equation directly relates dissolution rate to surface area, diffusion coefficient, boundary-layer thickness, and concentration gradient?

• Higuchi equation
• Noyes–Whitney/Nernst–Brunner equation
• Stokes–Einstein equation only
• Michaelis–Menten equation

Correct Answer: Noyes–Whitney/Nernst–Brunner equation

Q30. To meet BCS “high solubility” criteria for the highest dose strength across pH 1–6.8, which development strategy can be effective?

• Using only a hydrophobic lubricant
• Selecting an appropriate salt form with improved aqueous solubility
• Increasing tablet hardness
• Color coating the tablet

Correct Answer: Selecting an appropriate salt form with improved aqueous solubility

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