Drug dissolution, or the rate of in vitro drug release from drug product (primarily oral solid dosage form), has become an important aspect of bio-relevancy, particularly with the advent of new drug delivery systems and the increasing use of poorly soluble drugs. Those cases where poorly soluble and water-insoluble drugs are administered, drug bioavailability becomes dissolution rate limited. It all started in 1897 with the first reference to dissolution by an article published by Noyes and Whitney. They suggested a mathematical relationship, the well known Noyes-Whiney equation, which correlates rate of dissolution of a solid drug to its solubility gradient. A few years later in 1904, Nernst and Brunner studied the application of Fick's law of diffusion to the Noyes-Whiney equation. And by the 1950's, emphasis put on to the relationship of dissolution behavior to bioavailability of drug product. Dissolution testing became official first time in the USP XVIII in the year1970. Only twelve monographs contained dissolution requirement in the USP XVIII. And in the BP, digoxin tablet was the first monograph stipulating such requirement in 1977 BP addendum.
Through the use of in vitro drug release, or dissolution, it is possible to predict the in vivo performance of many drug products. This concept has been acknowledged by FDA, USA and is reflected by the numerous FDA guidances issued on dissolution testing. Guidances such as in vitro-in vivo correlation (IVIVC) and biopharmaceutics classification system (BCS) are receiving more attention worldwide from regulatory bodies. Dissolution testing has been accepted as a critical quality control tool and an aid to formulation development, not only by pharmaceutical industries but also by regulatory bodies. Over the last 20 years there have been significant advancements in dissolution testing, both in the apparatus modification and in the methodology of operation. Today it is becoming increasingly important aspect of IVIVC.
Dissolution testing apparatuses: The USP apparatus, considered robust and well standardized, consists of a container filled with dissolution medium. The apparatus has either a stirring basket or a stirring paddle that creates a flow around solid dosage form, promoting dissolution. These basket and paddle methods are used worldwide for dissolution testing for a variety of drug products. Today the USP includes seven apparatuses for immediate, modified, extended and delayed release products and transdermal products as well. The apparatuses 3 to 7 should be considered on the basis of their superiority for a particular drug product.
Recent activities in dissolution testing: In general, compendial dissolution standards are single-point dissolution tests. And this requirement is 70-80% of the stated drug product dissolved in 45 minutes. In recent years, FDA has placed more emphasis on dissolution profiles.
A dissolution profile can characterize a drug product more precisely than a single point dissolution test. A dissolution profile is recommended by FDA for SUPAC and biowaivers. In an attempt to reduce inter-laboratory variation in dissolution testing, the USP suggests use of chemical calibrators (prednisone tablet and salicylic acid tablet) to standardize the dissolution apparatus. The areas of most recent trend in dissolution testing apparatuses are fibre optic technology and fully automated dissolution apparatuses. The fibre optic detect cell is either located in the basket or paddle and permits continuous measurements without filtering and pumping of samples. Many organizations (Federation Internationale Pharmaceutique, FIP; Pharmaceutical Research and Manufacturers of Americas, PhRMA; and World Health Organization, WHO) are actively involved in the improvement and application of dissolution testing technique. There is a plethora of published studies that examine the increasing scientific attention being directed to dissolution testing.
The primary mission of in vitro dissolution testing is to provide a reasonable prediction of an oral solid dosage form's in vivo performance. Dissolution testing is considered today an important quality control test for measuring performance of a drug product. It is continuing to grow as a critical test to pharmaceutical analysis. Dissolution testing is extremely useful for many drug products that are considered to pose bioavailability problems. It is anticipated that dissolution testing will continue to grow as a meaningful process to help determine when dissolution testing is sufficient to grant a waiver for an in vivo bioequivalence study.
(The author is reader in Pharmacy Annamalai University, TN)