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PCB Pharmacist Registration practice questions

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Question 1Pharmaceutics and Pharmaceutical Technology

Which dosage form is designed to release drug at a controlled rate over an extended period after a single dose?

  1. Sublingual tablet
  2. Lyophilized powder for injection
  3. Sustained-release tablet Correct answer.
  4. Effervescent granule

Explanation

Sustained-release systems use rate-controlling polymers or coatings so that drug is liberated gradually, maintaining plasma levels over many hours and reducing dosing frequency. The other forms release drug rapidly or require reconstitution and injection.

Question 2Pharmaceutics and Pharmaceutical Technology

Which excipient is added to a tablet formulation primarily to promote disintegration of the compact?

  1. Colorant
  2. Binder
  3. Disintegrant Correct answer.
  4. Glidant

Explanation

Disintegrants such as croscarmellose sodium or starch swell or wick water into the tablet, breaking it into granules and particles to expose surface area for dissolution. Binders hold particles together, glidants improve powder flow, and colorants provide identification.

Question 3Pharmaceutics and Pharmaceutical Technology

In a suspension, which property is most directly improved by adding a suspending agent that raises vehicle viscosity?

  1. Drug solubility
  2. Sterility
  3. Sedimentation rate Correct answer.
  4. Taste masking

Explanation

According to Stokes' law, sedimentation velocity is inversely related to the viscosity of the dispersion medium, so thickening the vehicle slows settling and keeps particles suspended. Solubility, taste, and sterility are governed by other formulation factors.

Question 4Pharmaceutics and Pharmaceutical Technology

Which route of administration avoids first-pass hepatic metabolism most completely for a small lipophilic drug?

  1. Intramuscular
  2. Rectal (upper rectum)
  3. Oral
  4. Sublingual Correct answer.

Explanation

Drug absorbed from the sublingual mucosa drains into the systemic venous circulation, bypassing the portal vein and therefore hepatic first-pass metabolism. Oral absorption enters the portal circulation, and the upper rectum drains partly to the portal system.

Question 5Pharmaceutics and Pharmaceutical Technology

Which unit operation is used to reduce the particle size of a dry powder by impact and attrition in a rotating drum containing grinding media?

  1. Fluid-bed granulation
  2. Ball milling Correct answer.
  3. Freeze drying
  4. Spray drying

Explanation

A ball mill rotates a cylinder containing hard media; the tumbling media crush and shear the powder by impact and attrition, reducing particle size. Spray drying, granulation, and freeze drying build particles or dry liquids rather than comminute solids.

Question 6Pharmaceutics and Pharmaceutical Technology

Which statement describes the purpose of a preservative in a multiple-dose aqueous injection?

  1. It increases the solubility of the active drug.
  2. It sterilizes the product during terminal autoclaving.
  3. It neutralizes pyrogens in the formulation.
  4. It inhibits microbial growth introduced during repeated use. Correct answer.

Explanation

Preservatives such as benzyl alcohol or phenol suppress proliferation of microorganisms that may enter a multi-dose container after the stopper is punctured. They are not sterilants, do not destroy pyrogens, and are not solubilizers.

Question 7Pharmaceutics and Pharmaceutical Technology

Which term describes the amount of drug that reaches systemic circulation unchanged after administration?

  1. Half-life
  2. Clearance
  3. Volume of distribution
  4. Bioavailability Correct answer.

Explanation

Bioavailability expresses the fraction of the administered dose that reaches the systemic circulation in intact form, and for extravascular routes it is compared with an intravenous reference. Half-life, volume of distribution, and clearance are separate pharmacokinetic parameters.

Question 8Pharmaceutics and Pharmaceutical Technology

Which packaging material provides the best barrier against moisture vapor for a hygroscopic tablet?

  1. Polyvinyl chloride blister
  2. Paperboard carton
  3. Aluminum foil blister Correct answer.
  4. Cellophane wrap

Explanation

Aluminum foil is essentially impermeable to water vapor and light when pinhole-free, making it the preferred barrier for moisture-sensitive tablets. Paperboard, PVC, and cellophane transmit moisture vapor to varying degrees.

Question 9Pharmaceutics and Pharmaceutical Technology

A drug has poor aqueous solubility and is a weak base. Which strategy most reliably increases its apparent aqueous solubility in an oral solution?

  1. Adding a chelating agent
  2. Adjusting pH to below its pKa with an acid Correct answer.
  3. Increasing the ionic strength strongly
  4. Raising the pH well above its pKa

Explanation

For a weak base, lowering the pH protonates the molecule and converts it to the more water-soluble ionized form, raising apparent solubility. Chelation, ionic strength, and higher pH do not reliably increase solubility of a weak base.

Question 10Pharmaceutics and Pharmaceutical Technology

Which factor most increases the dissolution rate of a poorly soluble drug according to the Noyes-Whitney relationship?

  1. Increasing particle size
  2. Increasing the diffusion layer thickness
  3. Decreasing surface area
  4. Increasing surface area by micronization Correct answer.

Explanation

The Noyes-Whitney equation shows dissolution rate proportional to surface area and inversely related to diffusion layer thickness. Micronization increases surface area, so more drug contacts the dissolution medium per unit time.

Question 11Pharmaceutics and Pharmaceutical Technology

Which manufacturing method produces soft gelatin capsules by simultaneously filling and sealing two plasticized gelatin ribbons?

  1. Direct compression
  2. Rotary die process Correct answer.
  3. Dip molding
  4. Wet granulation

Explanation

In the rotary die process, two gelatin ribbons pass between rotating dies while fill is injected, and the dies cut and seal the capsule in one continuous operation. Dip molding makes hard gelatin shells, and compression and granulation are tablet processes.

Question 12Pharmaceutics and Pharmaceutical Technology

Which excipient function is served by magnesium stearate in a tablet formulation?

  1. Lubricant Correct answer.
  2. Binder
  3. Disintegrant
  4. Sweetener

Explanation

Magnesium stearate is a hydrophobic lubricant that reduces friction between the tablet and die wall during ejection. Overmixing or excess lubricant can retard disintegration and dissolution, so it is added in small amounts at the end of blending.

Question 13Pharmaceutics and Pharmaceutical Technology

A formulation team observes capping during tablet compression. Which change is most likely to reduce this defect?

  1. Reducing the depth of the die fill
  2. Adding more lubricant to the blend
  3. Increasing the compression force further
  4. Reducing the amount of fines in the granulation Correct answer.

Explanation

Capping often arises from entrapped air and poor bonding when granules contain excessive fines or are too dry. Reducing fines and optimizing granule properties improves air escape and interparticle bonding, reducing the tendency of the cap to separate.

Question 14Pharmaceutics and Pharmaceutical Technology

Which parameter is determined from a powder's Carr's compressibility index of about 30 percent?

  1. Very poor flow
  2. Excellent flow
  3. Good flow
  4. Poor flow Correct answer.

Explanation

Carr's index values of roughly 26 to 31 percent indicate poor flow, while values below about 15 percent indicate good to excellent flow and values above about 32 percent indicate very poor flow. The index is calculated from bulk and tapped densities.

Question 15Pharmaceutics and Pharmaceutical Technology

Which statement best explains why a drug in a hydrophobic matrix tablet shows first-order rather than zero-order release?

  1. Release depends on diffusion through a matrix whose path length increases as drug depletes. Correct answer.
  2. The tablet disintegrates immediately in the stomach.
  3. The drug is released only by osmotic pumping.
  4. The polymer erodes at a perfectly constant rate throughout.

Explanation

In a matrix system the dissolved drug diffuses through a progressively longer and more tortuous channel as the depletion zone deepens, so the release rate declines with time and follows first-order or square-root kinetics. Zero-order release requires a constant driving force or surface area.

Question 16Pharmaceutics and Pharmaceutical Technology

Which sterilization method is appropriate for a heat-labile ophthalmic solution in a sealed glass ampoule?

  1. Dry heat at 160 degrees Celsius
  2. Filtration through a 0.22 micron membrane Correct answer.
  3. Ethylene oxide gas treatment
  4. Moist heat at 121 degrees Celsius

Explanation

Filtration through a sterilizing-grade 0.22 micron membrane removes bacteria without exposing the heat-labile drug to destructive temperatures and is standard for such solutions. Moist heat and dry heat degrade thermolabile drugs, and ethylene oxide is unsuitable for aqueous solutions in sealed ampoules.

Question 17Pharmaceutics and Pharmaceutical Technology

Which test is used to confirm that a parenteral product is free from viable microorganisms?

  1. Particulate matter test
  2. Clarity test
  3. Sterility test Correct answer.
  4. Pyrogen test

Explanation

The sterility test incubates samples in suitable media to detect viable microorganisms. Pyrogen and endotoxin tests detect fever-causing substances, particulate matter tests count particles, and clarity tests detect visible particulates.

Question 18Pharmaceutics and Pharmaceutical Technology

Which factor is most important in determining the sedimentation volume of a flocculated suspension compared with a deflocculated one?

  1. Flocculated suspensions settle rapidly to a large, loosely packed sediment that redisperses easily. Correct answer.
  2. Deflocculated suspensions form a hard cake that cannot be redispersed.
  3. Flocculated suspensions settle slowly to a small, compact sediment.
  4. Deflocculated suspensions settle as loose flocs that are easy to resuspend.

Explanation

Floccules aggregate into loose, open structures that settle quickly but produce a high sedimentation volume and redisperse readily on shaking. Deflocculated particles settle slowly but pack tightly into a hard cake that is difficult to resuspend.

Question 19Pharmaceutics and Pharmaceutical Technology

Which pharmacokinetic parameter is calculated as dose divided by the area under the plasma concentration-time curve after intravenous bolus administration?

  1. Systemic clearance Correct answer.
  2. Elimination half-life
  3. Apparent volume of distribution
  4. Mean residence time

Explanation

After an intravenous dose, clearance equals dose divided by total area under the curve because the entire dose enters the systemic circulation. Half-life, volume of distribution, and residence time require additional relationships or moments of the curve.

Question 20Pharmaceutics and Pharmaceutical Technology

Which unit process is used to coat tablets with a thin polymer film using an aqueous or organic polymer solution sprayed onto a moving bed?

  1. Direct blending
  2. Dry granulation by roller compaction
  3. Pan coating with sugar syrup
  4. Fluid-bed coating Correct answer.

Explanation

Fluid-bed coating suspends tablets in an air stream while a polymer solution is sprayed on and dried, producing a thin, uniform film. Sugar pan coating builds thicker layers, and roller compaction and blending do not apply coatings.

Question 21Pharmaceutics and Pharmaceutical Technology

A pharmacist must prepare an isotonic solution containing a drug that contributes to tonicity. Which approach accounts for the drug's own contribution to osmotic pressure?

  1. Adding 0.9 percent sodium chloride regardless of drug content
  2. Using the sodium chloride equivalent method with the drug's E value Correct answer.
  3. Diluting the solution until the freezing point is zero
  4. Adding sodium chloride equivalent to 0.9 percent of the total weight

Explanation

The sodium chloride equivalent method converts the weight of drug present into its equivalent weight of sodium chloride using the E value, and the remainder needed to reach 0.9 percent is added. This accounts for the drug's own osmotic contribution.

Question 22Pharmaceutics and Pharmaceutical Technology

Which statement correctly describes the role of the diffusion layer in drug absorption from the gastrointestinal tract according to the pH-partition hypothesis?

  1. Un-ionized drug partitions into the lipid membrane, and the unstirred water layer can limit absorption of lipophilic drugs. Correct answer.
  2. The unstirred water layer enhances absorption of highly lipophilic drugs.
  3. Absorption is independent of the drug's ionization state.
  4. Ionized drug partitions readily into the lipid membrane.

Explanation

The pH-partition hypothesis holds that the un-ionized form partitions into the lipid membrane, while the aqueous unstirred layer adjacent to the membrane can become rate-limiting for very lipophilic drugs. Ionized species are poorly membrane-permeable.

Question 23Pharmaceutics and Pharmaceutical Technology

A drug follows linear one-compartment kinetics with a half-life of 6 hours. Approximately what fraction of the steady-state plasma concentration is reached after 18 hours of constant intravenous infusion?

  1. 99 percent
  2. 87.5 percent Correct answer.
  3. 75 percent
  4. 50 percent

Explanation

Steady state is approached exponentially with a half-life of 6 hours, so 18 hours equals three half-lives. The remaining fraction is 0.5 raised to the third power, or 12.5 percent, meaning about 87.5 percent of steady state is reached.

Question 24Pharmaceutics and Pharmaceutical Technology

Which mechanism explains why adding a highly water-soluble excipient can accelerate drug release from a hydrophilic matrix tablet?

  1. The excipient covalently crosslinks the polymer chains.
  2. The excipient increases the polymer's crystallinity.
  3. The excipient lowers the glass transition temperature of the polymer.
  4. The excipient dissolves and creates pores, increasing porosity and diffusional pathways. Correct answer.

Explanation

Soluble fillers leach out of the hydrated matrix, leaving pores that raise porosity and shorten the tortuous diffusion path, so drug release accelerates. Plasticization, crosslinking, and crystallinity changes act through different mechanisms.

Question 25Pharmaceutics and Pharmaceutical Technology

During scale-up of a high-shear wet granulation, which parameter is most useful for keeping the granulation endpoint comparable across batch sizes?

  1. Impeller tip speed Correct answer.
  2. Volume of the granulator bowl
  3. Number of binder additions
  4. Total batch weight

Explanation

Impeller tip speed normalizes the shear and chopper energy experienced by the powder across different bowl sizes, so granule growth and endpoint remain comparable during scale-up. Batch weight and bowl volume change with scale, and binder additions are process choices rather than scaling parameters.

Question 26Pharmaceutics and Pharmaceutical Technology

Which dosage form is designed to release drug at a controlled rate over an extended period after a single administration?

  1. Oral disintegrating tablet
  2. Extended-release tablet Correct answer.
  3. Chewable tablet
  4. Effervescent granule

Explanation

An extended-release dosage form is formulated so that drug is liberated gradually over a prolonged period, reducing dosing frequency and smoothing plasma concentrations. The other forms are designed for immediate or rapid drug liberation rather than prolonged release.

Question 27Pharmaceutics and Pharmaceutical Technology

Which property of a pharmaceutical powder is measured by the angle of repose?

  1. Moisture content of the granules
  2. Particle true density
  3. Flowability of the bulk powder Correct answer.
  4. Degree of crystallinity

Explanation

The angle of repose is the angle formed by a heap of powder poured onto a surface, and a smaller angle indicates better flow because interparticle friction is lower. It is therefore a bulk flow indicator, not a measure of density, moisture, or crystal form.

Question 28Pharmaceutics and Pharmaceutical Technology

A pharmacist prepares a solution by dissolving a drug in a vehicle containing propylene glycol and water. Which term best describes propylene glycol in this formulation?

  1. Buffer
  2. Disintegrant
  3. Suspending agent
  4. Co-solvent Correct answer.

Explanation

Propylene glycol is a water-miscible liquid that blends with water to lower the polarity of the vehicle and improve dissolution of poorly water-soluble drugs, which is the definition of a co-solvent. Suspending agents, disintegrants, and buffers serve unrelated functions in a formulation.

Question 29Pharmaceutics and Pharmaceutical Technology

A tablet formulation is found to have very low porosity and shows prolonged disintegration. Which change in the formulation is most likely to improve disintegration?

  1. Increasing the compression force applied
  2. Adding a higher proportion of a swelling disintegrant Correct answer.
  3. Reducing the proportion of water in the granulation liquid
  4. Coating the tablet with a hydrophobic polymer

Explanation

Disintegrants act by swelling or wicking water into the tablet, so increasing their proportion promotes rapid breakup of the compact. Lower porosity and harder compacts resist water penetration, so raising compression force or adding a hydrophobic coat would worsen rather than improve disintegration.

Question 30Pharmaceutics and Pharmaceutical Technology

A drug is to be formulated as a sterile suspension for intramuscular injection. Which combination of properties is most important for acceptable product quality and patient safety?

  1. Deliberate omission of sterilization because the vehicle is nonaqueous
  2. Reliance on a preservative alone to ensure the product is sterile
  3. Particle size small enough for syringeability and uniform dose, with sterile manufacture and controlled crystal form Correct answer.
  4. A high proportion of particles larger than 100 micrometres to slow dissolution and prolong action

Explanation

For an injectable suspension, particle size must be controlled so the product passes through a needle and delivers a uniform dose, and the product must be manufactured sterilely because a suspension cannot be terminally filtered. Crystal form and particle size also govern dissolution and release, so they must be characterized and controlled.

Question 31Pharmaceutical Chemistry and Medicinal Chemistry

Which functional group is present in a carboxylic acid but absent in an ester?

  1. A carbonyl group conjugated with an aromatic ring
  2. An ether linkage between two alkyl chains
  3. An acidic hydroxyl group attached to a carbonyl carbon Correct answer.
  4. A primary amine attached to a carbonyl carbon

Explanation

A carboxylic acid contains a carbonyl carbon bonded to a hydroxyl group, and this -OH is acidic because the conjugate base is resonance-stabilized. An ester replaces that acidic hydrogen with an alkyl or aryl group, so the acidic hydroxyl is absent.

Question 32Pharmaceutical Chemistry and Medicinal Chemistry

Which property of a drug molecule most directly determines its ability to cross a lipid bilayer by passive diffusion?

  1. Its melting point
  2. Its number of aromatic rings
  3. Its content of chiral centers
  4. Its molecular weight and lipophilicity Correct answer.

Explanation

Passive transcellular diffusion depends mainly on size and lipophilicity, which is why rules such as molecular weight under about 500 and moderate logP are used to predict oral absorption. Ionization also matters, since only the uncharged fraction permeates readily.

Question 33Pharmaceutical Chemistry and Medicinal Chemistry

What is the principal role of glucuronic acid conjugation in drug metabolism?

  1. It replaces the drug's carbonyl with a hydroxyl
  2. It activates the drug for receptor binding
  3. It increases water solubility to promote excretion Correct answer.
  4. It converts the drug into a more lipophilic species

Explanation

Glucuronidation attaches a polar sugar moiety, markedly increasing aqueous solubility and enabling biliary or renal elimination. It is a classic phase II conjugation reaction that generally terminates pharmacologic activity.

Question 34Pharmaceutical Chemistry and Medicinal Chemistry

Which structural feature is characteristic of penicillins?

  1. A beta-lactam ring fused to a six-membered dihydrothiazine ring
  2. A beta-lactam ring fused to a five-membered thiazolidine ring Correct answer.
  3. A macrocyclic lactone ring with a sugar substituent
  4. A peptide chain terminating in D-alanine

Explanation

Penicillins share a bicyclic nucleus in which the four-membered beta-lactam is fused to a saturated five-membered thiazolidine ring. Cephalosporins, by contrast, contain a six-membered dihydrothiazine ring.

Question 35Pharmaceutical Chemistry and Medicinal Chemistry

Which analytical technique is most commonly used to determine the molecular mass of a small-molecule drug?

  1. Mass spectrometry Correct answer.
  2. Polarimetry
  3. Flame photometry
  4. Ultraviolet-visible spectrophotometry

Explanation

Mass spectrometry ionizes molecules and separates them by mass-to-charge ratio, giving the molecular mass and often fragmentation information. UV-visible spectroscopy mainly probes chromophores and gives no direct mass.

Question 36Pharmaceutical Chemistry and Medicinal Chemistry

Which type of bond is primarily responsible for the secondary structure of a protein drug target?

  1. Peptide bonds linking amino acids
  2. Disulfide bonds between cysteine residues
  3. Ionic bonds between side chains
  4. Hydrogen bonds between backbone amide groups Correct answer.

Explanation

Secondary structure such as alpha helices and beta sheets arises from hydrogen bonding between backbone carbonyl and amide groups. Disulfide bridges stabilize tertiary structure, and peptide bonds are the primary backbone linkage.

Question 37Pharmaceutical Chemistry and Medicinal Chemistry

Which statement describes a prodrug?

  1. A drug formulated as a sustained-release tablet
  2. A metabolite that retains full receptor activity
  3. An inactive derivative that is converted to the active drug in the body Correct answer.
  4. A drug that binds irreversibly to its receptor

Explanation

A prodrug is a chemically modified, usually inactive form designed to improve absorption, distribution, or stability, and it undergoes metabolic or chemical conversion to release the active agent. Enalapril is a familiar example that is hydrolyzed to enalaprilat.

Question 38Pharmaceutical Chemistry and Medicinal Chemistry

A weak base drug with pKa 8.4 is placed in the small intestine at pH 6.0. Which statement best describes its ionization?

  1. It is predominantly deprotonated and neutral
  2. It is predominantly deprotonated and negatively charged
  3. It is equally protonated and deprotonated
  4. It is predominantly protonated and positively charged Correct answer.

Explanation

For a weak base, the protonated form predominates when pH is below the pKa. Because 6.0 is more than two units below 8.4, the Henderson-Hasselbalch equation predicts that well over 99 percent of the drug is protonated and carries a positive charge.

Question 39Pharmaceutical Chemistry and Medicinal Chemistry

Which modification of a lead compound is most likely to prolong its duration of action by slowing oxidative metabolism?

  1. Introducing a readily oxidized methyl group
  2. Adding a polar carboxylic acid group
  3. Blocking a metabolically labile position with a fluorine atom Correct answer.
  4. Reducing the molecular weight

Explanation

Fluorine is a bioisostere for hydrogen that resists oxidative attack and can block a site of cytochrome P450 hydroxylation, extending half-life. Adding a methyl group at a labile position typically increases, rather than decreases, oxidation.

Question 40Pharmaceutical Chemistry and Medicinal Chemistry

Two enantiomers of a drug are compared. Which property is expected to differ between them?

  1. Their melting point in an achiral solvent
  2. Their ultraviolet absorption maximum
  3. Their binding affinity at a chiral receptor site Correct answer.
  4. Their molecular formula

Explanation

Enantiomers have identical physical properties in achiral environments but can interact differently with chiral receptors, so potency and selectivity may differ. This is why single-enantiomer development is often pursued.

Question 41Pharmaceutical Chemistry and Medicinal Chemistry

Which structural change to a weakly acidic drug would most increase its aqueous solubility at physiological pH?

  1. Removing all ionizable groups
  2. Esterifying the acidic group
  3. Introducing a basic amine that can form a salt Correct answer.
  4. Adding a bulky lipophilic alkyl chain

Explanation

Adding an ionizable basic center allows salt formation and increases the charged, water-soluble fraction at physiological pH. Lipophilic additions and esterification reduce aqueous solubility.

Question 42Pharmaceutical Chemistry and Medicinal Chemistry

A compound shows high permeability but very low aqueous solubility. Which formulation strategy is most appropriate?

  1. Conversion to a highly crystalline polymorph
  2. Addition of a large excess of inorganic salt
  3. Amorphous solid dispersion with a polymer carrier Correct answer.
  4. Enteric coating of a compressed tablet

Explanation

For a Biopharmaceutics Classification System class II compound, dissolution is rate-limiting, so disrupting the crystal lattice through an amorphous solid dispersion can raise apparent solubility. Highly crystalline forms and salt addition would worsen the problem.

Question 43Pharmaceutical Chemistry and Medicinal Chemistry

Which reaction is the principal route by which phase I metabolism introduces a hydroxyl group into an aromatic ring?

  1. Cytochrome P450-catalyzed oxidation Correct answer.
  2. Nucleophilic aromatic substitution by glutathione
  3. Reductive amination
  4. Acetylation of an amine

Explanation

Cytochrome P450 enzymes catalyze aromatic hydroxylation through an oxidative mechanism, a hallmark phase I transformation. Acetylation and glutathione conjugation are phase II reactions.

Question 44Pharmaceutical Chemistry and Medicinal Chemistry

Which feature of the sulfonamide antibacterials explains their selective toxicity?

  1. They mimic a substrate of a microbial folate synthesis enzyme Correct answer.
  2. They alkylate bacterial ribosomes nonspecifically
  3. They inhibit a transporter found only in mammalian cells
  4. They bind directly to human DNA gyrase

Explanation

Sulfonamides are structural analogs of para-aminobenzoic acid and competitively inhibit dihydropteroate synthase in the microbial folate pathway. Humans obtain folate from the diet and lack this enzyme, giving selectivity.

Question 45Pharmaceutical Chemistry and Medicinal Chemistry

Which change is most likely to convert a potent but nonselective kinase inhibitor into a more selective agent?

  1. Increasing overall lipophilicity
  2. Exploiting a unique residue in the target binding pocket to add a specific interaction Correct answer.
  3. Removing all hydrogen-bond donors
  4. Adding a reactive electrophile

Explanation

Selectivity is usually gained by designing interactions with residues or conformational features unique to the target kinase. Broad increases in lipophilicity or reactive groups tend to raise off-target binding and toxicity.

Question 46Pharmaceutical Chemistry and Medicinal Chemistry

A drug is a substrate for P-glycoprotein. What is the most likely consequence for its pharmacokinetics?

  1. Increased oral bioavailability and tissue accumulation
  2. Faster hepatic phase II conjugation
  3. Reduced intestinal absorption and enhanced efflux from cells Correct answer.
  4. Greater plasma protein binding

Explanation

P-glycoprotein is an ATP-driven efflux transporter that pumps substrates out of enterocytes and other cells, limiting absorption and tissue penetration. Inhibiting the transporter can raise exposure, which is the basis for several drug interactions.

Question 47Pharmaceutical Chemistry and Medicinal Chemistry

Which molecular property is measured by the partition coefficient logP?

  1. Degree of ionization at a given pH
  2. Rate of hepatic clearance
  3. Binding affinity for plasma albumin
  4. Distribution of a neutral compound between octanol and water Correct answer.

Explanation

logP quantifies the equilibrium distribution of the uncharged form of a solute between 1-octanol and water, serving as a standard lipophilicity index. The pH-dependent version, logD, accounts for ionization.

Question 48Pharmaceutical Chemistry and Medicinal Chemistry

Which strategy best improves the oral bioavailability of a drug that is rapidly glucuronidated in the gut wall?

  1. Increasing the dose of the same compound
  2. Adding a second glucuronidation site
  3. Sterically hindering the conjugation site Correct answer.
  4. Converting the drug to a more lipophilic ester

Explanation

Blocking or sterically shielding the site of glucuronidation reduces first-pass conjugation and can raise systemic exposure. Adding another conjugation site or simply raising the dose does not solve the metabolic liability.

Question 49Pharmaceutical Chemistry and Medicinal Chemistry

Which interaction between a drug and its receptor is primarily responsible for high-affinity, reversible binding?

  1. Covalent bond formation
  2. Chelation of a metal ion
  3. Disulfide exchange
  4. Complementary hydrogen bonding and hydrophobic contact Correct answer.

Explanation

Reversible high-affinity binding typically arises from a combination of hydrogen bonds, hydrophobic contacts, and ionic interactions in a complementary pocket. Covalent bonds produce essentially irreversible inhibition.

Question 50Pharmaceutical Chemistry and Medicinal Chemistry

Which property of a lead compound is most improved by reducing its topological polar surface area while keeping lipophilicity moderate?

  1. Plasma protein binding
  2. Hepatic clearance
  3. Aqueous solubility
  4. Blood-brain barrier penetration Correct answer.

Explanation

Lower polar surface area favors passive passage across the blood-brain barrier, provided lipophilicity remains in a moderate range. Excessive reduction of polarity, however, can reduce solubility.