Relationship among disintegration, dissolution, and absorption

Relationship among disintegration, dissolution, and absorption

Oral absorption from the GI tract takes place from the drug in aqueous solution at the site of absorption. Therefore, a tablet must disintegrate into primary drug particles and release the drug, that is, the drug should dis-solve in the fluids at the site of absorption, before absorption can take place (Figure 20.5). However, tablets that are intended for chewing or SR do not have to undergo disintegration. Excipients for tablet formulation affect the rates of disintegration, dissolution, and absorption. Systemic absorption of most products consists of a succession of rate processes, such as

·           Disintegration of the DP into granules and primary drug particles

·           Dissolution of the drug from the granules and primary drug particles in an aqueous environment

·           Absorption of drug solution across cell membranes into the systemic circulation

Figure 20.5 Relationship among disintegration, dissolution, and drug absorption from an intact tablet.

Tablet disintegration, dissolution, and drug absorption are influenced by physicochemical properties (e.g., solubility, compactibility, density, and flow) and stability (e.g., to heat, moisture, and light) of the DS; its com-patibility with the excipients in the dosage form; site and extent of drug absorption in the GI tract; and dose. In these processes, the rate at which drug reaches the circulatory system is determined by the slowest step in the sequence. Disintegration of a tablet is usually more rapid than drug dis-solution and absorption. For the drug that has poor aqueous solubility, the rate at which the drug dissolves (dissolution) is often the slowest step, and therefore exerts a rate-limiting effect on drug bioavailability. In contrast, for the drug that has a high aqueous solubility, the dissolution rate is rapid and the rate at which the drug crosses or permeates cell membranes is the slowest or rate-limiting step.

Aqueous solubility and permeability across the intestinal mucosa form the basis of identifying the relative difficulty in formulating drugs for oral delivery through what is known as the biopharmaceutics classification sys-tem (BCS). BCS classifies both the rate of drug permeation and drug solu-bility relative to the highest dose in two categories: high and low. Thus, all drugs can be divided into four distinct categories: I—high solubility, high permeability; II—low solubility, high permeability; III—high solubility, low permeability; and IV—low solubility, low permeability. This classifi-cation system has been used to understand and influence (by formulation design) the oral pharmacokinetics of drugs.