JNTU B. Pharmacy III BIOPHARMACEUTICS AND PHARMACOKINETICS Previous Question Paper (February/March - 2022 - R17)

Drug absorption across biological membranes occurs primarily through the following four mechanisms:

1. Passive Diffusion: This is the most common mechanism where drug molecules move from a region of higher concentration to a region of lower concentration. It is a non-energy-requiring process that follows Fick's Law of Diffusion, where the rate of transport is proportional to the concentration gradient and the surface area of the membrane.
2. Carrier-Mediated Transport: This involves specialized membrane proteins that act as carriers. It includes Facilitated Diffusion, which is concentration-gradient driven but faster than passive diffusion, and Active Transport, which requires metabolic energy (ATP) to move drugs against a concentration gradient.
3. Vesicular Transport (Endocytosis): This mechanism involves the engulfment of drug molecules by the cell membrane to form vesicles. It is categorized into Phagocytosis (cell eating of large particles) and Pinocytosis (cell drinking of fluid droplets).
4. Pore Transport (Convective Transport): Small, water-soluble molecules (e.g., urea, water, ions) pass through aqueous-filled protein channels or pores in the membrane. This process is driven by hydrostatic or osmotic pressure differences.

Dosage form factors significantly influence the rate and extent of drug absorption by controlling the release of the drug from the delivery system:

• Disintegration Time: For solid dosage forms like tablets and capsules, the drug must first disintegrate into smaller particles. A longer disintegration time delays the availability of the drug for dissolution, thereby slowing absorption.
• Dissolution Rate: This is often the rate-limiting step for poorly water-soluble drugs. Factors such as particle size, crystal form (polymorphism), and the presence of surfactants in the formulation directly affect how quickly the drug dissolves in the gastrointestinal fluids.
• Excipients: Additives such as binders, lubricants, and disintegrants can either facilitate or hinder absorption. For example, hydrophobic lubricants like magnesium stearate can coat drug particles and retard dissolution, while surfactants can enhance the wetting and solubility of hydrophobic drugs.
• Product Age and Storage: Changes in the physical state of the dosage form over time, such as hardening of tablets or crystal growth, can reduce the dissolution rate and bioavailability of the drug.
• Manufacturing Variables: The compression force used during tableting affects the porosity and hardness of the tablet, which in turn dictates the rate of water penetration and subsequent disintegration.