For solid, extended-release oral forms, the dissolution test should show that (a) the product is stable under acidic stomach conditions (e.g., pH 1.2); and b) release into intestinal pH. If a USP method is available, resolution must be performed using that method. If there is no USP method, the DBE recommends for all concentrations of a DR product that dissolution tests be performed under acidic conditions (pH 1.2) for 2 h, followed by neutral media (e.g., pH 6.8). In general, DR products should be resistant to acids under dissolution test conditions (8,9). At present, the DBE does not require additional multimedia resolution testing for DR products that have biphasic clearance (10). Semi-solid dosage forms, including creams, gels, lotions and ointments, are typically intended for topical application (25). At this time, DBE does not request in vitro release test data in support of applications for removal authorization from ANDA for generics in this category. The DBE does not require an in vitro release test for the authorisation of generic semi-solid preparations; The test is also not required as a routine batch-to-batch quality control test. Similarly, the DBE does not consider in vitro release assays as a substitute for in vivo studies on EB of generic semi-solid medicinal products; Therefore, in vitro release tests cannot be used to justify biological exemptions for these products.
However, in vitro release tests for semi-solid medicinal products may be used to support certain types of post-authorisation modifications to generic semi-solid formulations. Such in vitro release test methods to compare the performance of certain types of formulations before and after modification can be developed using an open-chamber diffusion cell system such as a Franz cell system. Therefore, a validated in vitro release test method developed using an open-chamber diffusion cell system, such as a Franz cell system, is useful to support some scaling and post-approval changes of generic semi-solid drugs (25). In vitro dissolution (resolution) tests play a crucial role in the life cycle of a generic drug. When developing a dissolution test for a generic drug to be marketed in the United States, researchers should consider official methods and standards published in the United States Pharmacopeia (USP). The USP describes seven different dissolution devices with which an appropriate dissolution method can be developed based on the properties of the drug (5,6). The dissolution method should be sufficiently robust and reproducible for daily operation, transferable between laboratories and distinguishable enough to distinguish changes that may affect the in vivo performance of the device (7). The Division of Bioequivalence (DBE) of the Bureau of Generic Drugs, U.S. Center for Drug Evaluation and Research, FDA, requires researchers to perform comparative dissolution tests with at least 12 dosage units of test and reference products each. Resolution data shall be generated by sampling the resolution medium at appropriate times to characterize the resolution profile. It is proposed to use three to four or more dissolution times (other than zero) with uniform spacing for rapid dissolution of drugs (8). For the resolution of sustained-release (ER) formulations, longer sampling times are proposed to adequately characterize the complete dissolution profile.
The DBE evaluates the results of in vitro data submitted by ANDA applicants to investigate the performance of the drug`s release mechanism in the presence of alcohol and to consider the results when deciding whether two products are bioequivalent (16, 17). So these are the general reasons why most resolution methods require 500-900ml of resolution media. With these volumes, you can also succeed with most products. This volume is usually small enough that you have a sufficient concentration to read the samples in an HPLC or UV. The volume is also usually high enough to dissolve the drug without resorting to excessive surfactants or exotic media.