Pharmacology: Drug Absorption and Stability
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What primarily determines the absorption of weak electrolytes in the gastrointestinal tract?

  • The presence of food in the stomach
  • The total dosage of the drug administered
  • The molecular weight of the drug
  • The unionized form of the drug at the site of absorption (correct)

    • Which factor does NOT play a role in the pH-partition theory regarding drug absorption?

  • The presence of enzymes in the gastrointestinal tract (correct)
  • The lipid solubility of the drug
  • The ionization of the drug
  • The drug's ability to pass through the lipid barrier

    • According to the Henderson-Hasselbalch equation for weakly acidic drugs, what does an increase in pH indicate?

  • A greater degree of ionization of the drug (correct)
  • An increase in the drug's stability
  • A higher concentration of the unionized form of the drug
  • A lower pKa value for the drug

    • Which statement is true regarding the gastrointestinal tract's lipid barrier?

    <p>Unionized drugs can pass across the barrier through passive diffusion.</p> Signup and view all the answers

    In the context of drug stability, which factor is most critical for maintaining efficacy during gastrointestinal transit?

    <p>Hydrolysis rates in stomach acid</p> Signup and view all the answers

    What effect does changing a weakly acidic drug from its free acid form to a basic salt form have on the pH of the diffusion layer?

    <p>It increases the pH of the diffusion layer.</p> Signup and view all the answers

    Which polymorph of chloramphenicol palmitate is considered the most stable?

    <p>Form A</p> Signup and view all the answers

    What is the main characteristic of the amorphous form of a drug compared to its crystalline form?

    <p>It dissolves more rapidly.</p> Signup and view all the answers

    What is the effect of increased solvation on the solubility of a crystalline drug?

    <p>It decreases solubility.</p> Signup and view all the answers

    What is the term for a crystalline form produced when a drug associates with solvent molecules?

    <p>Solvate</p> Signup and view all the answers

    Which form of a weakly acidic drug would precipitate out in gastric fluid with a low bulk pH?

    <p>The free acid form</p> Signup and view all the answers

    What is characteristic of metastable polymorphs in relation to solubility?

    <p>They are more soluble than stable forms.</p> Signup and view all the answers

    How do the dissolution characteristics of different polymorphs of a drug impact its bioavailability?

    <p>Different polymorphs have varying dissolution rates affecting bioavailability.</p> Signup and view all the answers

    At what pH level will a weakly acidic drug (pKa 3.0) be predominantly unionized?

    <p>pH 1.2</p> Signup and view all the answers

    Which of the following factors is NOT a limitation of the pH-partition hypothesis?

    <p>The molecular weight of the drug</p> Signup and view all the answers

    What factor primarily influences the aqueous solubility of weak electrolytes?

    <p>pH of the solution</p> Signup and view all the answers

    For a weakly basic drug (pKa 5), at which pH is it predominantly unionized?

    <p>pH 6.8</p> Signup and view all the answers

    How can enteric coated tablets protect drugs like erythromycin from degradation?

    <p>They resist gastric fluid and dissolve in less acidic pH</p> Signup and view all the answers

    What is the relationship between lipid solubility and drug absorption after oral administration?

    <p>Lower lipid solubility leads to poorer absorption.</p> Signup and view all the answers

    What is the impact of partition coefficient on drug absorption?

    <p>Higher partition coefficient correlates with higher absorption.</p> Signup and view all the answers

    What is a disadvantage of complexation with certain dietary components?

    <p>Formation of poorly absorbed complexes</p> Signup and view all the answers

    Which of the following drugs is likely to require administration by injection due to poor absorption after oral administration?

    <p>Gentamicin</p> Signup and view all the answers

    Which of the following is true regarding the adsorption of co-administered drugs?

    <p>It leads to poor absorption of the drug</p> Signup and view all the answers

    Why might bioavailability differ between solvated and nonsolvated forms of a drug?

    <p>They have different dissolution rates</p> Signup and view all the answers

    Which type of compounds are absorbed despite being ionized over the entire pH range of the gastrointestinal tract?

    <p>Quaternary ammonium compounds</p> Signup and view all the answers

    What is the formula for calculating the partition coefficient?

    <p>p = [L] conc / [W] conc</p> Signup and view all the answers

    Which drug interaction involves an excipient within the dosage form leading to poor absorption?

    <p>Mucin + Streptomycin</p> Signup and view all the answers

    What effect does pH have on the dissolution rate of weak electrolyte drugs in the GIT?

    <p>Dissolution rate varies with the pH in the diffusion layer</p> Signup and view all the answers

    What is the role of prodrugs like erythromycin stearate in drug absorption?

    <p>They improve bioavailability by being activated in the intestines</p> Signup and view all the answers

    What is the first step in the process leading to drug absorption?

    <p>Disintegration</p> Signup and view all the answers

    Which model describes a drug dissolution process where the rate is proportional to the concentration difference?

    <p>First order model</p> Signup and view all the answers

    What determines the rate at which a drug reaches the circulatory system?

    <p>The slowest step in the sequence</p> Signup and view all the answers

    Which of the following apparatus is used according to USP for drug dissolution?

    <p>Flow Through Cell Apparatus</p> Signup and view all the answers

    Which apparatus is specifically used for extended-release drug products according to compendial standards?

    <p>Reciprocating cylinder</p> Signup and view all the answers

    In the Noyes-Whitney equation, what does the variable 'h' represent?

    <p>Thickness of the stagnant layer</p> Signup and view all the answers

    What type of drugs does the Paddle over disk apparatus primarily test?

    <p>Transdermal drug products</p> Signup and view all the answers

    What effect does the presence of food in the gastrointestinal tract have on drug dissolution?

    <p>It reduces the rate of diffusion of drug molecules.</p> Signup and view all the answers

    How does gastric and intestinal motility affect the thickness of the diffusion layer around drug particles?

    <p>Increased motility decreases the thickness.</p> Signup and view all the answers

    Which factor increases the dissolution rate of a drug through micellization?

    <p>Presence of surfactants in gastric juice.</p> Signup and view all the answers

    What is the relationship between the intrinsic solubility of a drug and its dissolution rate?

    <p>Dissolution rate is directly proportional to intrinsic solubility.</p> Signup and view all the answers

    Which method of particle size reduction can improve drug dissolution rate?

    <p>Implementing solid dispersions in PEG's.</p> Signup and view all the answers

    What is the effect of increasing fluid intake in the diet on drug dissolution?

    <p>It decreases the concentration of the drug in solution.</p> Signup and view all the answers

    Which of the following factors does NOT affect the diffusion coefficient of a drug?

    <p>Intrinsic solubility of the drug.</p> Signup and view all the answers

    Study Notes

    Physical-Chemical & Formulation Properties

    • The lecture covers physical-chemical factors affecting oral absorption.
    • Key factors include pH-partition theory, lipid solubility of drugs, dissolution, drug stability and hydrolysis in the gastrointestinal tract (GIT), complexation, and adsorption.

    Physical-Chemical Factors Affecting Oral Absorption

    • pH-partition theory: Drugs (weak electrolytes) exist in ionized and unionized forms, with only the unionized form crossing the lipid barrier of the gastrointestinal epithelia.
    • The absorption of a weak electrolyte is determined by the extent of its unionized form at the absorption site.
    • Lipid Solubility of Drugs: Lipophilicity is critical in drug discovery
    • Polar molecules (low lipid solubility, log P < 0) are often poorly absorbed orally, requiring injection.
    • Dissolution: Many drugs are administered in solid dosage forms and must dissolve before absorption.
    • Dissolution is a critical step in drug absorption.
    • The slowest step in the sequence of disintegration, dissolution, and absorption is the rate-limiting step.
    • Various models explain dissolution, including diffusion layer model, Dankwert's model, and interfacial barrier model.

    1- pH-Partition Theory

    • The gastrointestinal epithelia act as a lipid barrier.
    • Drugs absorbed via passive diffusion; lipid-soluble drugs pass across the barrier.
    • Ionized forms (weak electrolytes) of drugs are poorly absorbed, whereas the unionized forms (lipid-soluble) are absorbed.
    • Absorption of weak electrolytes depends on the extent of their unionized form at the absorption site.

    2- Lipid Solubility of Drugs

    • Lipophilicity (lipid-loving property) of a drug is critical in its absorption and discovery.
    • Drugs with low lipid solubility (log P < 0) may be poorly absorbed orally.
    • Partition coefficient (p) relates water and lipid solubility ([L] conc / [W] conc where [L] is lipid phase and [W] is aqueous phase).
    • Higher the p-value, more absorption is observed

    3- Drug Dissolution

    • Drugs in solid dosage forms must dissolve before absorption.
    • Dissolution steps are disintegration, dissolution, and absorption, and the slowest step is crucial.
    • Rate-limiting step determines the overall process.

    4- Drug Stability and Hydrolysis in GIT

    • Drugs susceptible to hydrolysis in the GIT may have reduced bioavailability.
    • Aqueous solubility of weak electrolytes relies on pH.
    • Dissolution rate in GIT will be influenced via solubility and pH.

    5- Complexation

    • Drug complexation can occur in the dosage form or within gastrointestinal fluids.
    • Interactions (beneficial or detrimental to absorption) may occur between the drug and components (dietary, excipients).

    6- Adsorption

    • Insoluble substances can adsorb co-administered drugs causing poor absorption.
    • Adsorption decreases the effective concentration of the drug.

    Formulation Factors Affecting Oral Absorption

    • Drug formulation plays a vital role in delivery to the absorption site.
    • Drug must be in solution within GIT.
    • Bioavailability of drugs can be reduced in certain dosage forms (solid dosage forms tend to have lower bioavailability than aqueous solutions).
    • Excipients are added to improve functional properties.

    Various models/theories which explain dissolution

    • Diffusion layer model/Film theory
    • Dankwert's Model (Penetration or Surface renewal theory)
    • Interfacial barrier model (Double Barrier Mechanism OR Limited Solvation Theory)

    Types of models of mechanism of drug release

    • Zero order
    • First order
    • Higuchi model
    • Korsemeyer Peppas Model
    • Hixon Crowel plot

    Official dissolution Apparatus

    • Basket apparatus
    • Paddle apparatus
    • Flow Through Cell Apparatus
    • Different apparatuses are categorized based on BP (British Pharmacopoeia) and USP (United States Pharmacopeia) classifications

    Dissolution process of a salt form of a weakly acidic drug in gastric fluid

    • The pH of the diffusion layer surrounding a drug affects the absorption process.
    • Salts tend to be more rapidly dissolved at a higher pH.

    E - Crystal form (Polymorphism)

    • Some drugs exist in different crystal forms (polymorphs).
    • These polymorphs (e.g., A, B, C forms) have different solubility and dissolution behaviors.
    • Amorphous forms dissolve faster, potentially leading to differences in bioavailability compared to crystalline forms.

    Solvates (Hydrates)

    • Drugs may form solvates (e.g., hydrates) by associating with solvent molecules.
    • The solvation level affects solubility and dissolution rate.

    Various Factors Affecting Drug Dissolution rate

    • Physiological factors (Diffusion coefficient, Thickness of diffusion layer, Concentration drug in solution in the bulk of GIT fluids)
    • Physicochemical factors (surface area, diffusion coefficient, solubility, salts)
    • pH in GIT

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    Physical-Chemical & Formulation Properties PDF

    Description

    This quiz explores key concepts in pharmacology related to drug absorption, particularly for weak electrolytes. Questions focus on the pH-partition theory, the Henderson-Hasselbalch equation, and factors influencing drug stability in the gastrointestinal tract. Test your understanding of drug forms, solubility, and polymorphism.

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