BCS (Biopharmaceutic Classification System) is a classification approach in which drugs (APIs) are divided into four classes based on the extent (high or low) of their aqueous solubility and permeability through the GI tract wall, in particular intestinal. In this regard, these four classes are: (I) High Solubility and High Permeability drugs, (II) Low Solubility and High Permeability drugs, (III) High Solubility and Low Permeability drugs and, (IV) Low solubility and Low Permeability drugs.  It is very important to note that BCS relates only to drugs (APIs) and their characteristics and not to the products.

These two factors (solubility and permeability) indeed play a critical role, keeping all other factors equal, for the evaluation of absorption characteristics of drugs in humans. For example, if four drugs, one from each class in equal doses, are administered in solution forms, all would show differences in absorption through GI tract or appearances in the blood stream depending on their solubility/permeability characteristics. Potentially, the drug in the group I would show fast and high absorption (least hindrance to absorption), drug in group IV would show slow and erratic absorption (highest hindrance) while drugs in group II and III would show absorption in between. Therefore, BCS certainly provides a good basis for assessing potential absorption behavior of a drug in humans. Continue reading →

Like any other product evaluation, pharmaceutical products are also evaluated using various analytical tests. Following the product development stage, these tests become quality control or assurance tests and are required to be conducted to establish the quality of the products for sale. Commonly, pharmacopeial, such as USP, standards are followed for this purpose.

For solid oral pharmaceutical products such as tablets and capsules, these tests include: (1) Identification – to establish or confirm the expected identity of the drug within a product; (2) Assay or Potency – to establish the presence of the expected amount of drug in the product; (3) Uniformity of Content – to establish unit to unit (tablet/capsule) variation in the drug amount (4) Drug release/dissolution test – to establish that the drug would be released from the product in an expected and reproducible manner. Continue reading →

A number of guidances are available from different regulatory agencies, in particular the US FDA, to facilitate and expedite drug products development and evaluations. These guidances are related to dissolution method developments, apparatus calibration and product evaluations. In many cases, these guidances and related practices are commonly referred to by their acronyms, such as BCS, IVIVC, SUPAC, bio-waivers, similarity factor (F2) QbD, PVT, mechanical calibration. Examples of such commonly referred guidance documents are listed under the publications section.

It is important to note that these guidances solely or significantly depend on the use of dissolution (Paddle and Basket) apparatuses. Therefore, success or applications of these guidances are dependent on the outcome from these apparatuses.

In recent years, it has generally been recognised that Paddle and Basket apparatuses do not provide relevant and reproducible dissolution results. This is because of the poor hydrodynamics (or lack of efficient stirring and mixing) within dissolution vessels. Therefore, intended benefits from the use of the guidance documents may also become suspect.

Appropriate use and interpretation of the guidance documents require relevant and reproducible results. This may be achieved by conducting dissolution tests using apparatuses which are free from the deficiencies of Paddle and Basket, that is apparatuses with improved and efficient stirring and mixing environments.

FDA provides choices of experimental conditions for conducting drug dissolution/release tests for various drug products (Link). In total there are 789 entries in the database, including 228 where readers are referred to the USP monographs and 16 without suggestions and the sponsors are to develop their own. Therefore, there remains 545 (789-228-16) entries, which are used for the trend analysis. Continue reading →