The pharmacokinetic journey of drugs from solid oral dosage forms into systemic circulation is multifaceted. It begins with disintegration, a prerequisite ensuring a solid dosage form's subdivision into minute particles. Dissolution occurs next as these granulated entities solubilize in gastrointestinal fluids. This solubilization is crucial for the succeeding stage, permeation, which describes the traversal of the drug across the intestinal membrane and its subsequent entry into the blood circulation.
Critically, drug absorption kinetics can be impeded by either the rate of dissolution or permeation. The dissolution rate is a limiting factor, particularly for lipophilic substances and drugs with inherently low aqueous solubility, including extended-release formulations. Permeation, on the other hand, governs the absorption rate in hydrophilic drugs, dictating their transport through lipid bilayers.
The Biopharmaceutics Classification System (BCS) stratifies drugs into four classes based on their solubility and permeability attributes. Class I compounds exhibit high solubility and permeability and are readily absorbed. Class II drugs are hindered by poor solubility, Class III by diminished permeability, and Class IV face absorption challenges attributed to both low solubility and permeability. Examples include diltiazem (Class I), nifedipine (Class II), insulin (Class III), and taxol (Class IV).
A critical pharmacokinetic parameter, dissolution rate, is also quantified as the rate at which a drug transitions from a solid state to a solubilized form within a given solvent under controlled conditions. Solubility challenges substantially impact the dissolution rate, notably for compounds with aqueous solubility below 1-2 mg/ml within the gastrointestinal pH range of 2 to 8. Nevertheless, drugs such as cisapride overcome low intrinsic solubility through a swift dissolution rate and small therapeutic dose, ensuring sufficient absorption within the gastrointestinal transit period. Dissolution dynamics correlate more with overall drug absorption and bioavailability than absolute solubility.
