The physicochemical characteristics of drugs play a crucial role in formulating stable and bioavailable drug products. The solubility of a drug, governed by the varying pH along the GI tract and its dissociation constant (pKa), is pivotal in determining its ionization state and absorption rate. Notably, weak acids and bases remain unionized and are absorbed more rapidly.
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating drug-fluid interactions and accelerating dissolution. Due to their instability in the stomach's acidic environment, certain drugs can be coated with an acid-resistant film, called an enteric coating, to prevent degradation until they reach the intestines for absorption. Despite poor aqueous solubility, lipophilic drugs can absorb effectively due to their high partition coefficients that allow passage through cell membranes. Also, drugs can exist in various structural forms, such as amorphous, polymorphs, and solvates. Interestingly, amorphous forms, exist in a high-energy state, making them more readily soluble than crystals, enhancing drug absorption. These findings underline the importance of considering a drug's physicochemical properties in designing effective and bioavailable drug products.
