It often puzzles people as to how one should select one approach over the other. It is often considered that for quality control (QC) purposes one may use single-point approach, while during product and/or method development stages one may use multi-point sampling approach. The single point approach is often derived from multi-point sampling used during the product development stage. It is important to note that for ER products usually there are no single-point tolerances, even for QC purposes. Should, or do, these approaches provide different outcomes? For example, with the multi-point sampling approach dissolution may be measured at 5, 10, 15, 20, 30, 45 and 60 minutes, and for QC purposes a single sampling time of say 30 minutes may be chosen. The dissolution results at 30 minutes should exactly be the same whether one uses multi-point or single point approach as dissolution is property of the product which remained the same.
For selecting an approach (multiple or single) one may use the following rationale:
It appears that the confusion arises from the division of the tests as either drug dissolution or drug release tests. Often people consider that if the test is referred to a dissolution test then one may use single point sampling, while for a release test one should consider multi-point sampling. However, in reality dissolution and release tests are one and the same thing. If fact, one should consider the test as a drug release based dissolution test. Therefore, it is very important to note that whether it is a QC test or a test for product/method development for an IR or ER product, it is a release-based dissolution test. One monitors (establishes) release characteristics of a drug from a product by measuring the content (dissolution) of the drug in the medium. It does not matter if one takes a sample at 5 minutes or 24 hours, if the drug is released, one needs to take a sample to measure the drug in the medium (dissolution). Therefore, for drug release/dissolution purposes one sample should be sufficient, whether at 5 minutes or 24 hours, to establish whether the drug is releasable from the product or not.
On the other hand, if one were to consider that in addition to the extent of drug release, its rate of release is important as well then one has to measure dissolution at multiple sampling times. It is not a matter of preference, or choice or issues related to type of product (IR or ER), it is the need to establish the rate of drug release/dissolution for a particular product. For example, if it is required for a product to release/dissolve a drug quickly for prompt/immediate action such as painkillers, then there is no point in monitoring the rate. One should decide how fast drug release/dissolution is required and then sample at that time to establish the required dissolution. It is generally assumed that if a drug is released within an hour or so the body may not recognize the differences in the rates, so there may not be a need for going for the extra step. On the other hand, if it is shown that drug is to be released at a certain rate to complete dissolution even for an IR product, then multi-point sampling becomes a need and has to be monitored at different sampling times. Monitoring of the rate of release/dissolution for ER product is critical, to avoid any potential adverse effect (dose dumping or abrupt release) or lack of efficacy (slower than expected).
An important conclusion from the preceding discussion is that the type of sampling approach depends on the expected requirement of drug release/dissolution for the product action. A formulator/analyst is expected to fulfil this requirement.
