Drug Absorption - Oral Administration

Drug Absorption - Oral

• Epithelial cell layer controls drug absorption; intestinal epithelium acts as a major barrier.
• Transcellular pathway facilitates drug absorption by allowing drug molecules to partition into cell membranes.
• Drug passage occurs at the apical side (mucosa) then through the basolateral side into systemic circulation, mostly via passive transport.
• Passive transport is energy-independent, occurs through simple diffusion, and follows concentration gradients.
• Predominantly applicable to small lipophilic compounds that can penetrate the phospholipid bilayer of cell membranes.

Lipophilic and Hydrophilic

• Lipophilic substances dissolve well in lipids and non-polar solvents.
• Hydrophilic substances dissolve well in water and polar solvents.
• Principle "like dissolves like"; lipophilic molecules tend to permeate cell membranes due to compatibility with lipid bilayer.

Measuring Drug Lipophilicity

• Simulated absorption using a mixture of lipophilic solvent (octanol) and hydrophilic solvent (water).
• Distribution between the two phases indicates drug's lipophilicity; complete presence in octanol indicates high lipophilicity.

Partition Coefficient and Log P

• Higher Log P values indicate higher lipophilicity; lower Log P values indicate greater hydrophilicity.
• Optimal Log P values determine gastrointestinal absorption efficiency for oral drugs.
• Excessive Log P (e.g., > 5) can lead to bioaccumulation risks (e.g., polychlorinated biphenyls).

Drug Absorption Constraints

• Ionization significantly impacts drug absorption; weak acids and bases can change lipophilicity based on medium pH (Log D).
• Basic functional groups include amines; acidic functional groups include carboxylic acids and phenols.

Oral Pharmaceutical Formulation

• Oral pharmaceuticals, like tablets, contain active pharmaceutical ingredients (API) and excipients which influence bioavailability.
• API characteristics (physical state, particle size) affect absorption.
• Excipients (fillers and lubricants) assist in drug manufacturing and release.

Bioequivalence

• Bioequivalence studies evaluate the comparability of bioavailability between different formulations of the same drug.
• Differences in absorption can arise from variations in drug release kinetics.
• Pharmacokinetic parameters are assessed by comparing serum concentrations after administration.

Targeted Drug Delivery

• Passive Targeting: Utilizes hypoxic conditions within tumors for localized drug activation.
• Active Targeting: Involves drug conjugation to antibodies for specific tissue recognition.
• Example: Ivacaftor for cystic fibrosis, altered by replacing hydrogen atoms with deuterium to enhance pharmacokinetics by reducing metabolic rates and improving efficacy and safety.