Drug release dissolution rates

Drug release/dissolution rate Plate angular velocity... 

Biopharmaceutic studies (in vitro) Drug release/dissolution Measurement of the rate of drug dissolved under specified conditions... 

In-vitro bioavailahility tests usually form part of the criteria for evaluating the individual batches of a product. These are based on monitoring the rate of release of the drug substance from the pharmaceutical form, usually by observing the dissolution rates of tablets or capsules. 

Figure 4.52. Coefficients of variation that reflect both tablet to tablet and analytical variability. For formulation B, particularly strengths 2 and 3, the drop in CV with higher cumulative release (a - b) is marked, cf. Fig, 4.50. When the dissolution rate is high, individual differences dominate, while towards the end analytical uncertainty is all that remains. The very low CVs obtained with strength 3 of formulation A ( 0.7-0.8%, data offset by +10% for clarity) are indicative of the analytical uncertainty. Because content uniformity is harder to achieve the lower the drug-to-excipient ratio, this pattern is not unexpected.

M Bisrat, C Nystrom. Physicochemical aspects of drug release. VIII. The relation between particle size and surface specific dissolution rate in agitated suspensions. Int J Pharm 47 223-231, 1988. 

A reported application of canonical analysis involved a novel combination of the canonical form of the regression equation with a computer-aided grid search technique to optimize controlled drug release from a pellet system prepared by extrusion and spheronization [28,29]. Formulation factors were used as independent variables, and in vitro dissolution was the main response, or dependent variable. Both a minimum and a maximum drug release rate was predicted and verified by preparation and testing of the predicted formulations. Excellent agreement between the predicted values and the actual values was evident for the four-component pellet system in this study. 

P. Sathe, J. Venitz, and L. Lesko, Evaluation of truncated areas in the assessment of bioequivalence of immediate release formulations of drugs with long half lives and CMax with different dissolution rates, Pharm. Res, 16, 939 (1999). 

Since dosage forms contain more than just active drug, it is of practical interest to understand how the various components from a multicomponent solid influence their own dissolution and release. Nelson [18] was one of the first pharma-ceuticists to ponder this question and perform the initial dissolution studies. Unfortunately, Nelson initially considered the dissolution of interacting solids (benzoic acid + trisodium phosphate), which is a more complicated and more complex situation than simple multicomponent dissolution of noninteracting solids. Nelson did show that for his benzoic acid and trisodium phosphate pellets, there was a maximum increase in benzoic acid dissolution in water at a mole fraction ratio of 2 1 (benzoic acid trisodium phosphate) and that the benzoic acid dissolution rate associated with the maximum rate was some 40 times greater than that of benzoic acid alone. 

EL Parrot, DE Wurster, T Higuchi. Investigation of drug release from solids I. Some factors influencing the dissolution rate. J Am Pharm Assoc 44 269-273, 1955. 

Mechanisms of dissolution kinetics of crystals have been intensively studied in the pharmaceutical domain, because the rate of dissolution affects the bioavailability of drug crystals. Many efforts have been made to describe the crystal dissolution behavior. A variety of empirical or semi-empirical models have been used to describe drug dissolution or release from formulations [1-6]. Noyes and Whitney published the first quantitative study of the dissolution process in 1897 [7]. They found that the dissolution process is diffusion controlled and involves no chemical reaction. The Noyes-Whitney equation simply states that the dissolution rate is directly proportional to the difference between the solubility and the solution concentration ... 

E. K. Anderberg, M. Bisrat, C. Nystrom. Physicochemical aspects of drug release. VII. The effect of surfactant concentration and drug particle size on solubility and dissolution rate of felodipine, a sparingly soluble drug. Int. I. Pharm. 1988, 47, 67-77. 

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