Dissolution testing
In the pharmaceutical industry, drug dissolution testing is routinely used to provide critical in vitro drug release information for both quality control purposes, i.e., to assess batch-to-batch consistency of solid oral dosage forms such as tablets, and drug development, i.e., to predict in vivo drug release profiles. There are three typical situations where dissolution testing plays a vital role: formulation and optimization decisions: during product development, for products where dissolution performance is a critical quality attribute, both the product formulation and the manufacturing process are optimized based on achieving specific dissolution targets. Equivalence decisions: during generic product development, and also when implementing post-approval process or formulation changes, similarity of in vitro dissolution profiles between the reference product and its generic or modified version are one of the key requirements for regulatory approval decisions. Product compliance and release decisions: during routine manufacturing, dissolution outcomes are very often one of the criteria used to make product release decisions.
The main objective of developing and evaluating an IVIVC is to establish the dissolution test as a surrogate for human studies, as stated by the Food and Drug Administration. Analytical data from drug dissolution testing are sufficient in many cases to establish safety and efficacy of a drug product without in vivo tests, following minor formulation and manufacturing changes. Thus, the dissolution testing which is conducted in dissolution apparatus must be able to provide accurate and reproducible results.
Equipment
Several dissolution apparatuses exist. In United States Pharmacopeia General Chapter <711> Dissolution, there are four dissolution apparatuses standardized and specified. They are:- USP Dissolution Apparatus 1 – Basket
- USP Dissolution Apparatus 2 – Paddle
- USP Dissolution Apparatus 3 – Reciprocating Cylinder
- USP Dissolution Apparatus 4 – Flow-Through Cell
- USP Dissolution Apparatus 5 - Reciprocating Disk
General Method
The vessels of the dissolution method are usually either partially immersed in a water bath solution or heated by a jacket. An apparatus is used on solution within the vessels for a predetermined amount of time which depends on the method for the particular drug. The dissolution medium within the vessels are heated to 37 °C with an acceptable difference of ± 0.5 °CThe performances of dissolution apparatuses are highly dependent on hydrodynamics due to the nature of dissolution testing. The designs of the dissolution apparatuses and the ways of operating dissolution apparatuses have huge impacts on the hydrodynamics, thus the performances. Hydrodynamic studies in dissolution apparatuses were carried out by researchers over the past few years with both experimental methods and numerical modeling such as Computational Fluid Dynamics. The main target was USP Dissolution Apparatus 2. The reason is that many researchers suspect that USP Dissolution Apparatus 2 provides inconsistent and sometimes faulty data. The hydrodynamic studies of USP Dissolution Apparatus 2 mentioned above clearly showed that it does have intrinsic hydrodynamic issues which could result in problems. In 2005, Professor Piero Armenante from New Jersey Institute of Technology and Professor Fernando Muzzio from Rutgers University submitted a technical report to the FDA. In this technical report, the intrinsic hydrodynamic issues with USP Dissolution Apparatus 2 based on the research findings of Armenante's group and Muzzio's group were discussed.
More recently, hydrodynamic studies were conducted in USP Dissolution Apparatus 4.