Crystalline Powder

In reality, most dosage forms are tablets containing a crystalline powder of the drug substance. Unlike a solution dose, the amount of drug dissolved in the intestine will increase with time, as the dosage form disintegrates and releases crystalline drug particles. There are no simple pharmacokinetic equations to describe this process. Solution dosage forms of the same drug are unlikely to show differences in the rate and extent of absorption and, therefore, are likely to be bioequivalent. Solution dosage forms will present the total dose in the form of drug that can be absorbed (in solution) with the amount of drug in the lumen falling exponentially, as drug is absorbed at the same rate. However, immediate-release solid dosage forms are likely to have slightly different rates of disintegration due to the choice of tablet excipients and the manufacturing process and potentially larger differences in dissolution rate depending on the drug particle size and the efficiency of wetting provided by the formulation. There is a mechanistically based theory to describe the kinetics of dissolution that will be discussed, and it will be shown how dissolution theory can be used to determine if the combined effect of disintegration and wetting are having a significant impact on drug absorption. Before getting into the more sophisticated treatment of dissolution, the absorption rate equation discussed earlier provides the starting point for a very simple and useful analysis of situations that might present difficulties in drug absorption. Recalling Equation, the integration of this equation over a specified period of time gives the mass of drug absorbed from the GI tract. If nothing limited the amount of drug that could be administered as a solution to the GI tract, then there would be no limit to the amount of drug that could be absorbed. However, drug solubility presents a limit to the amount of drug that can exist as a solution in the GI tract. Any solid crystalline drug administered would continue to dissolve unless its concentration equaled its solubility. At this point, no further drug would dissolve until some of the drug in solution was absorbed. If enough solid drugs were administered so that the rate of dissolution was equal to the rate of absorption, a temporary steady state would exist where the concentration of drug in the GI tract would It can be seen that if enough solid crystalline drug is given so that the rate of dissolution can match the rate of absorption to keep the concentration of drug in the GI tract at its solubility, the rate of absorption becomes constant. If equation is integrated over the typical residence time, that drug would remain in the small intestine tr, with this integration called the maximum absorbable dose (MAD) (11), a simple calculation is the result.