Physicochemical properties and biological action MCQs With Answer

Introduction: Understanding physicochemical properties and biological action is essential for B. Pharm students preparing for examinations and practice. This concise guide covers key concepts—pKa, solubility, logP/logD, permeability, dissolution, protein binding, ADME, BCS classification, polymorphism, salt forms, and formulation strategies—and explains how these properties influence drug absorption, distribution, metabolism, elimination, and pharmacological effect. Emphasis on lipophilicity, ionization, hydrogen bonding, molecular size and polar surface area helps bridge theory with formulation and therapeutic outcome. Clear MCQs reinforce mechanisms such as ion trapping, micellar solubilization, prodrug design, and stability considerations, improving problem-solving for pharmaceutics and pharmacokinetics. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What does pKa represent for a drug molecule?

• The pH at which the drug is completely ionized
• The dissociation equilibrium constant expressed as pH where 50% of species is ionized
• The partition coefficient between octanol and water
• The maximum solubility of the drug in water

Correct Answer: The dissociation equilibrium constant expressed as pH where 50% of species is ionized

Q2. Which definition best describes logP?

• The logarithm of aqueous solubility
• The distribution coefficient of all ionic species between octanol and water at a given pH
• The partition coefficient of the unionized drug between octanol and water
• The diffusion coefficient of a drug across a membrane

Correct Answer: The partition coefficient of the unionized drug between octanol and water

Q3. How does logD differ from logP?

• logD measures only unionized drug partitioning
• logD is pH-dependent and includes both ionized and unionized species
• logD is always equal to logP at any pH
• logD refers only to distribution into tissues

Correct Answer: logD is pH-dependent and includes both ionized and unionized species

Q4. For which calculation is the Henderson–Hasselbalch equation primarily used?

• Estimating molecular weight from solubility
• Predicting dissolution rate from particle size
• Calculating the ratio of ionized to unionized drug at a given pH
• Determining partition coefficient in octanol

Correct Answer: Calculating the ratio of ionized to unionized drug at a given pH

Q5. How does ionization of a drug generally affect aqueous solubility?

• Ionized forms are typically less soluble in water
• Ionization has no effect on solubility
• Ionized forms are generally more soluble in water than unionized forms
• Unionized forms always precipitate in water

Correct Answer: Ionized forms are generally more soluble in water than unionized forms

Q6. What is the typical effect of increasing lipophilicity on passive membrane permeability?

• Permeability always decreases with increased lipophilicity
• Permeability generally increases with lipophilicity up to an optimal point
• Lipophilicity has no effect on permeability
• Highly lipophilic molecules are always impermeable

Correct Answer: Permeability generally increases with lipophilicity up to an optimal point

Q7. Which polar surface area (PSA) value is most favorable for blood–brain barrier penetration?

• PSA > 200 Ų
• PSA between 140–200 Ų
• PSA < 90 Ų
• PSA has no relation to BBB penetration

Correct Answer: PSA < 90 Ų

Q8. The pH-partition hypothesis states which of the following?

• Ionic species cross membranes more readily than unionized species
• Unionized species cross biological membranes more readily than ionized species
• All drugs cross membranes equally regardless of ionization
• Only charged drugs are absorbed by passive diffusion

Correct Answer: Unionized species cross biological membranes more readily than ionized species

Q9. Which factors appear in the Noyes–Whitney equation for dissolution rate?

• Molecular weight and refractive index
• Surface area, diffusion coefficient, concentration gradient and thickness of diffusion layer
• LogP and pKa only
• Boiling point and melting point

Correct Answer: Surface area, diffusion coefficient, concentration gradient and thickness of diffusion layer

Q10. On what two properties is the Biopharmaceutics Classification System (BCS) based?

• Melting point and crystal habit
• Solubility and permeability
• pKa and logP only
• Protein binding and half-life

Correct Answer: Solubility and permeability

Q11. What is ion trapping?

• Accumulation of non-ionized drug in acidic compartments
• Enzyme-catalyzed binding of drug to ions
• Accumulation of the ionized form of a drug on the side of a membrane where it predominates due to pH differences
• Formation of ionic salts to increase solubility

Correct Answer: Accumulation of the ionized form of a drug on the side of a membrane where it predominates due to pH differences

Q12. How does high plasma protein binding affect pharmacologically active drug concentration?

• Increases free drug concentration in plasma
• Decreases free drug concentration because only unbound drug is pharmacologically active
• Has no effect on free drug concentration
• Transforms the drug into an inactive metabolite

Correct Answer: Decreases free drug concentration because only unbound drug is pharmacologically active

Q13. Why is salt formation commonly used in drug development?

• To increase melting point only
• To improve solubility, dissolution rate and sometimes stability
• To make drugs non-ionizable permanently
• To increase molecular weight

Correct Answer: To improve solubility, dissolution rate and sometimes stability

Q14. What is the main advantage of using liposomes in drug delivery?

• They always decrease drug half-life
• They enable entrapment and targeted delivery of hydrophilic and lipophilic drugs, modifying pharmacokinetics
• They eliminate the need for solubility enhancement
• They convert all drugs into prodrugs

Correct Answer: They enable entrapment and targeted delivery of hydrophilic and lipophilic drugs, modifying pharmacokinetics

Q15. What does the critical micelle concentration (CMC) indicate?

• The concentration above which surfactant molecules aggregate to form micelles
• The minimum concentration required for drug ionization
• The pH at which micelles dissociate
• The partition coefficient of surfactants

Correct Answer: The concentration above which surfactant molecules aggregate to form micelles

Q16. How do surfactants enhance solubility of poorly soluble drugs?

• By decreasing the drug’s pKa
• By micellar solubilization, improving wetting and reducing interfacial tension
• By permanently ionizing the drug
• By increasing particle crystallinity

Correct Answer: By micellar solubilization, improving wetting and reducing interfacial tension

Q17. What is the effect of increasing the number of hydrogen bond donors on membrane permeability?

• Increases permeability by enhancing lipophilicity
• Decreases permeability because hydrogen bonding with water reduces membrane crossing
• No effect on permeability
• Always increases BBB penetration

Correct Answer: Decreases permeability because hydrogen bonding with water reduces membrane crossing

Q18. Which logP range is generally considered favorable for oral drug permeability and balanced solubility?

• logP < -2
• logP between 1 and 3
• logP > 7
• logP exactly equal to 5

Correct Answer: logP between 1 and 3

Q19. What is the primary purpose of designing a prodrug?

• To reduce molecular weight
• To improve solubility, permeability, stability or targeted delivery by metabolic conversion to the active drug
• To eliminate the need for clinical trials
• To permanently block pharmacological activity

Correct Answer: To improve solubility, permeability, stability or targeted delivery by metabolic conversion to the active drug

Q20. How can polymorphism in a drug substance affect its performance?

• Polymorphism only affects color
• Different polymorphs can have different solubility, dissolution rates and stability, impacting bioavailability
• All polymorphs have identical solubility and dissolution
• Polymorphism eliminates the need for formulation studies

Correct Answer: Different polymorphs can have different solubility, dissolution rates and stability, impacting bioavailability

Q21. A weak acid drug with pKa 4.5 is in plasma at pH 7.4. What is the predominant form?

• Predominantly unionized
• Predominantly ionized (deprotonated)
• Exactly 50% ionized
• Completely non-absorbable

Correct Answer: Predominantly ionized (deprotonated)

Q22. For a weak base, Henderson–Hasselbalch can be used to calculate which ratio?

• Ratio of protonated (ionized) to unprotonated (unionized) base
• Ratio of melting point to solubility
• Ratio of logP to logD
• Ratio of protein binding to clearance

Correct Answer: Ratio of protonated (ionized) to unprotonated (unionized) base

Q23. How does increasing molecular weight generally affect oral absorption?

• Higher molecular weight generally favors passive diffusion
• Molecular weight has no influence on absorption
• Higher molecular weight generally decreases membrane permeability and absorption
• Higher molecular weight always increases bioavailability

Correct Answer: Higher molecular weight generally decreases membrane permeability and absorption

Q24. What is polar surface area (PSA) used to predict?

• The drug’s color in solution
• Permeability and oral absorption; low PSA favors membrane crossing
• Only protein binding propensity
• Melting point of crystalline drugs

Correct Answer: Permeability and oral absorption; low PSA favors membrane crossing

Q25. Which method is considered the reference technique for measuring logP?

• PAMPA assay
• Shake-flask method using octanol–water partitioning
• Caco-2 permeability assay
• Mass spectrometry without partitioning

Correct Answer: Shake-flask method using octanol–water partitioning

Q26. How do ionizable functional groups generally influence blood–brain barrier penetration?

• Ionizable groups always enhance BBB penetration
• Bearing ionizable groups typically reduces BBB penetration because they increase polarity and reduce passive diffusion
• Ionizable groups convert drugs into prodrugs for BBB entry
• Ionizable groups are irrelevant for BBB crossing

Correct Answer: Bearing ionizable groups typically reduces BBB penetration because they increase polarity and reduce passive diffusion

Q27. What does amphiphilicity mean in the context of drug molecules?

• A molecule that is only hydrophobic
• A molecule with both hydrophilic and hydrophobic regions, promoting interactions with membranes and micelles
• A molecule that cannot dissolve in water
• A molecule with no functional groups

Correct Answer: A molecule with both hydrophilic and hydrophobic regions, promoting interactions with membranes and micelles

Q28. For BCS class II drugs, which factor is most commonly rate-limiting for oral absorption?

• Permeability across the intestinal wall
• Dissolution and solubility in gastrointestinal fluids
• Protein binding in plasma
• Hepatic clearance

Correct Answer: Dissolution and solubility in gastrointestinal fluids

Q29. What does LogS denote?

• Logarithm of the solubility in water; negative values indicate low solubility
• Logarithm of partition coefficient in octanol
• pKa of a drug
• Permeability coefficient in PAMPA

Correct Answer: Logarithm of the solubility in water; negative values indicate low solubility

Q30. How does gastric pH typically affect absorption of a weak base?

• Acidic stomach pH protonates weak bases, making them more unionized and easily absorbed
• Acidic stomach pH protonates weak bases, making them ionized and less readily absorbed in the stomach
• Gastric pH has no effect on weak bases
• Weak bases are always insoluble in gastric fluid

Correct Answer: Acidic stomach pH protonates weak bases, making them ionized and less readily absorbed in the stomach

Q31. What is the aim of salt screening during drug development?

• To find a salt form that optimizes solubility, stability, manufacturability and bioavailability
• To decrease the drug’s molecular complexity only
• To ensure the drug is always unionized
• To remove all polymorphs

Correct Answer: To find a salt form that optimizes solubility, stability, manufacturability and bioavailability

Q32. Why are enteric coatings used for some oral tablets?

• To ensure immediate release in the stomach
• To prevent release in the stomach and allow release in the intestine, protecting drug or stomach
• To convert drugs into salts
• To increase melting point

Correct Answer: To prevent release in the stomach and allow release in the intestine, protecting drug or stomach

Q33. Which statement differentiates PAMPA from Caco-2 permeability assays?

• PAMPA measures active transport while Caco-2 measures only passive diffusion
• PAMPA models passive permeability across an artificial membrane; Caco-2 includes cellular transporters and efflux mechanisms
• Caco-2 is used only for protein binding
• They are identical in mechanisms assessed

Correct Answer: PAMPA models passive permeability across an artificial membrane; Caco-2 includes cellular transporters and efflux mechanisms

Q34. How is absolute oral bioavailability (F) determined experimentally?

• By comparing AUC after oral dosing to AUC after intravenous dosing, corrected for dose
• From the drug’s pKa alone
• From the logP and logS values only
• By measuring only peak plasma concentration (Cmax)

Correct Answer: By comparing AUC after oral dosing to AUC after intravenous dosing, corrected for dose

Q35. What effect does first-pass hepatic metabolism have on oral bioavailability?

• First-pass metabolism increases oral bioavailability
• First-pass metabolism has no effect on bioavailability
• First-pass metabolism reduces oral bioavailability by metabolizing drug before systemic circulation
• First-pass metabolism only occurs for intravenous drugs

Correct Answer: First-pass metabolism reduces oral bioavailability by metabolizing drug before systemic circulation

Q36. How does lipophilicity generally influence volume of distribution (Vd)?

• Increased lipophilicity tends to increase Vd due to tissue partitioning
• Lipophilicity has no effect on Vd
• Increased lipophilicity always decreases Vd
• Lipophilicity only affects clearance, not Vd

Correct Answer: Increased lipophilicity tends to increase Vd due to tissue partitioning

Q37. Which guideline summarizes physicochemical rules predictive of oral druglikeness?

• Henderson–Hasselbalch rules
• Lipinski’s Rule of Five
• Arrhenius criteria
• Michaelis–Menten rules

Correct Answer: Lipinski’s Rule of Five

Q38. For which class of drugs are oil-in-water emulsions commonly used to improve oral delivery?

• Highly water-soluble drugs needing taste masking
• Lipophilic drugs to enhance solubilization and absorption
• Drugs that are gases at room temperature
• Drugs that are already highly permeable and soluble

Correct Answer: Lipophilic drugs to enhance solubilization and absorption

Q39. How do surfactants enhance oral bioavailability beyond micellar solubilization?

• By increasing drug melting point
• By improving wetting, reducing surface tension, stabilizing supersaturated solutions and sometimes inhibiting efflux transporters
• By converting drugs into crystalline forms
• By eliminating first-pass metabolism

Correct Answer: By improving wetting, reducing surface tension, stabilizing supersaturated solutions and sometimes inhibiting efflux transporters

Q40. What is the main pharmaceutical benefit of micronization of drug particles?

• To increase particle crystallinity
• To reduce particle size, increase surface area and enhance dissolution rate
• To make drugs more lipophilic
• To convert drugs into salts

Correct Answer: To reduce particle size, increase surface area and enhance dissolution rate

Q41. What is ion-pairing in formulation science used for?

• To make drugs more polar
• To pair oppositely charged molecules to increase lipophilicity and membrane permeability
• To neutralize toxicity permanently
• To decrease drug stability

Correct Answer: To pair oppositely charged molecules to increase lipophilicity and membrane permeability

Q42. How does alkalinization of urine influence renal excretion of weak acids?

• Alkalinization decreases excretion of weak acids by reducing ionization
• Alkalinization increases excretion of weak acids by increasing ionization and trapping in urine
• Urine pH has no effect on weak acid excretion
• Alkalinization only affects protein binding

Correct Answer: Alkalinization increases excretion of weak acids by increasing ionization and trapping in urine

Q43. Why is only the unbound fraction of a drug typically subject to clearance?

• Protein-bound drug is irreversibly inactivated
• Only unbound drug is free to cross membranes, interact with enzymes and be filtered/cleared
• Bound drug is always rapidly cleared
• Clearance depends only on logP

Correct Answer: Only unbound drug is free to cross membranes, interact with enzymes and be filtered/cleared

Q44. How can salt forms change the thermal properties of a drug substance?

• Salt forms never change thermal properties
• Salt formation can alter melting point and crystallinity, affecting stability and processing
• Salt forms always reduce melting point to zero
• Salt formation only affects color

Correct Answer: Salt formation can alter melting point and crystallinity, affecting stability and processing

Q45. What effect can chirality have on a drug’s biological action?

• Enantiomers always have identical pharmacokinetics and pharmacodynamics
• Enantiomers can differ in potency, efficacy, metabolism and toxicity
• Chirality only affects solubility
• Chirality is irrelevant in drug design

Correct Answer: Enantiomers can differ in potency, efficacy, metabolism and toxicity

Q46. What defines a zwitterion at physiological pH?

• A molecule that is entirely nonpolar
• A molecule that carries both positive and negative charges but is overall neutral
• A molecule that is permanently ionized as an anion only
• A molecule that cannot dissolve in water

Correct Answer: A molecule that carries both positive and negative charges but is overall neutral

Q47. Which PSA threshold is commonly associated with good intestinal absorption?

• PSA > 200 Ų
• PSA < 140 Ų
• PSA exactly 180 Ų
• PSA is not related to absorption

Correct Answer: PSA < 140 Ų

Q48. Which degradation pathways are routinely evaluated in chemical stability studies?

• Only photodegradation
• Hydrolysis, oxidation, photodegradation and thermal degradation
• Only microbial contamination
• Only changes in particle size

Correct Answer: Hydrolysis, oxidation, photodegradation and thermal degradation

Q49. How do cosolvents increase the solubility of poorly soluble drugs?

• By increasing the polarity of the solvent system and improving drug solvation
• By chemically converting the drug to an ion
• By increasing particle size
• By removing functional groups from the drug

Correct Answer: By increasing the polarity of the solvent system and improving drug solvation

Q50. What general trend is observed between logD and pH for an ionizable drug?

• logD is independent of pH
• logD increases when the drug is more ionized at that pH
• logD decreases at pH values where the drug is predominantly ionized, reflecting reduced lipophilicity
• logD always equals logP

Correct Answer: logD decreases at pH values where the drug is predominantly ionized, reflecting reduced lipophilicity

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com