Drug product dissolution profile

The BCS also predicts the possibility of obtaining an in vitro/in vivo correlation. Justification of a biowaiver is based on a combination of the BCS classification of the drug substance and a drug product dissolution profile comparison. In all these instances, an anchor with a bioavailable product is established. Specifically, to obtain a biowaiver for an IR generic product ... 

Low-permeability, high-solubility drugs—Multipoint dissolution profile should be performed in the application/compendial medium at 15,30,45,60, and 120min or until an asymptote is reached. The dissolution profile of the proposed and currently used product formulations should be similar. 

High-permeability, low-solubility drugs—Multipoint dissolution profiles should be performed in water, 0.1 N HC1, and USP buffer media at pH 4.5, 6.5, and 7.5 (five different profiles) for the proposed and currently accepted formulations. Adequate sampling should be performed at 15,30,45,60, and 120min until either 90% of drug from the drug product is... 

C. Determining Drug Product Dissolution Characteristics and Dissolution Profile Similarity... 

Within the realm of physical reality, and most important in pharmaceutical systems, the unconstrained optimization problem is almost nonexistent. There are always restrictions that the formulator wishes to place or must place on a system, and in pharmaceuticals, many of these restrictions are in competition. For example, it is unreasonable to assume, as just described, that the hardest tablet possible would also have the lowest compression and ejection forces and the fastest disintegration time and dissolution profile. It is sometimes necessary to trade off properties, that is, to sacrifice one characteristic for another. Thus, the primary objective may not be to optimize absolutely (i.e., a maxima or minima), but to realize an overall pre selected or desired result for each characteristic or parameter. Drug products are often developed by teaching an effective compromise between competing characteristics to achieve the best formulation and process within a given set of restrictions. 

Chow SC, Ki FYC. Statistical comparison between dissolution profiles of drug products. J Biopharm Stat 1997 7 241-258. 

The method for the evaluation of similarity of dissolution profiles depends on dissolution characteristic of the reference and test drug product. If both formulations (average value of n = 12 each) dissolve at least 85% of label claim within 15 min, dissolution profiles are generally assumed as similar and no further testing or data analysis is required. 

Accuracy. Sample solutions of known concentration (e.g., spiked placebo) are used for the accuracy determination. Experimental work may be organized so that the same stock solutions are used to prepare both linearity and accuracy solutions. The accuracy solution must be exposed to normal test conditions (e.g., mixing in a heated dissolution vessel). Determine any bias that is caused by the sampling and analysis of the solutions. If a dissolution profile of the drug product is required, accuracy determinations at different concentrations of the required profile will need to be performed (e.g., at 40, 75, and 110% of theoretical release). The results are reported as percent theory. 

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