Dissolution compendial requirements

The Joint Panel proposed no in vivo requirements, but individual dissolution testing requirements were adopted in 12 compendial monographs. USP tests measured the time to attain a specified amount dissolved, whereas NF used the more workable test for the amount dissolved at a specified time. Controversy with respect to equipment selection and methodology raged at the time of the first official dissolution tests. As more laboratories entered the field, and experience (and mistakes ) accumulated, the period 1970-1980 was one of intensive refinement of official test methods and dissolution test equipment. 

Compendial Requirements of Dissolution Testing—European Pharmacopoeia, Japanese Pharmacopoeia, United States... 

INTRODUCTION AND IMPLEMENTATION OF COMPENDIAL DISSOLUTION TEST REQUIREMENTS... 

USP recognition of the need to control the in vitro dissolution performance of oral products by some level of compendial requirement was evidenced by the formation of a joint USP-NF panel on physiological availability in 1967. The USP... 

Notification and updated batch record Stability Application/ compendial requirements plus multipoint dissolution profiles in three other media (e.g., water, 0.1/VHC1, and USP buffer media at pH 4.5 and 6.8) until >80% of drug released or an asymptote is reached Apply some statistical test (f2 test) for comparing dissolution profiles No biostudy... 

Dissolution document None beyond app. /compendial requirements... 

Evaluating the results from development and/or scale-up batches of compressed tablets employs the use of control charting techniques, process capability analysis, and prediction intervals as described earlier. The techniques apply equally well to in-process measurements of hardness, thickness, and tablet weight, and compendial requirements such as assay, dose uniformity by content uniformity, and dissolution. 

The documentation necessary to support this type of change are application/ compendial release requirements, batch records, and stability data for one batch with 3 months accelerated stability data in supplement and one batch on long-term stability. Dissolution data requirements depend on three scenarios known as cases that cover a high/low permeability and a high/low drug solubility, as shown in Table 2. No in vivo bioequivalence data are necessary for this submission if the... 

Early optimism about the possibility of in vitro-in vivo correlation was tempered by the need for a performance test that would yield reproducible results (10). Even though not necessarily correlated to bioavailability, dissolution requirements were seen as useful in controlling variables in formulation or processing. Thus, from the start, sources of variability in the results were seen as factors to be minimized in any proposed compendial method. 

Chemistry—Identify location of new site and updated batch records. No other documentation is required beyond application/compendial release requirements, although one batch produced at the new site should be placed on long-term stability and the data should be reported in the annual report. Dissolution data other than normal release requirements are not required nor is in vivo bioequivalence testing required. 

Dissolution documentation—None beyond application/compendial release requirements. 

Delayed release In addition to application/compendial release requirements, a multipoint dissolution profile should be obtained during the buffer stage... 

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