Evaluating the dissolution of a candidate molecule for an activepharmaceutical ingredient (API) before it is developed into amedicinal product has proven to be fundamental in the developmentof solid dosage forms for oral use that contain poorly soluble drugs(classes II and IV of the Biopharmaceutics Classification System[BCS]), since in these cases, dissolution is considered to be a limitingstep in absorption.1,2In the current scenario, the majority of molecules that are nowavailable or under development present this characteristic and teststhat enable to predict the release of the active substance can providevaluable data, facilitating the work of formulators, directly resultingin economy of resources and reduction in the time required tolaunching newmedicinal products.3−5Among the tests available, intrinsic dissolution enables thedissolution analysis of a pure drug, in a similar fashion to aconventional test. Accordingly, an apparatus that maintains aconstant surface area of the drug exposed to the medium must beused, since, contrary to solubility, intrinsic dissolution is not relatedto equilibrium, but rather the speed with which the drug is releasedfrom the matrix to the dissolution medium.6,7Intrinsic dissolution has been used for many years to charac-terize APIs, especially in preformulation studies, and it is especiallyuseful because of the small quantity of sample that is necessary toconduct the tests, as well as the fact that it may be applied both inthe stages prior to development (more precisely, in the prospectionof new chemical entities), the selection of raw material at thepreformulation stage and in the routine analysis of raw material ina quality assurance laboratory.4,8 Table 4.1 lists some examples ofintrinsic dissolution applications.

This Stimuli article discusses the approach for the development of a new general chapter on solubility determination for veterinary drug products. Possible procedures are discussed, with emphasis on the shake-flask method. Recommendations are included on the test conditions for products to treat dogs and cattle. The Expert Panel welcomes comments from the public and stakeholders.

A primary challenge for the pharmaceutical laboratory is to maximize throughput with optimum compliance. A technique-dependent test like dissolution is a primary target for implementing varying levels of automation, from semiautomated sampling equipment to fully robotic systems. Instrumentation flexibility will be required in the laboratory of the future to minimize the potential for error caused by manual intervention and to fully utilize the dissolution apparatus with automated sampling and onand offline UV or HPLC analytical systems. This article offers suggestions for determining the level of automation needed to obtain peak performance based on the product(s), laboratory requirements, and regulatory compliance associated with laboratory automation.

The concept of small-volume dissolution arises from the need to determine the dissolution rate from low-dose, generally high potency drugs or drugs with analytical techniques that are not very sensitive. Novel drug delivery products including subcutaneous implants, ocular systems, microspheres, nanospheres, and combination products such as drug-eluting stents (DES) have demanded more from traditional dissolution and drug-release apparatus. To maintain quantitative levels of analyte during the dissolution test, a reduction in vessel volume accompanied by an alteration of compendial dissolution apparatus may be required (1). The utilization of small-volume dissolution apparatus stems from the need to provide accurate, reliable data for decision-making during drug development stages and assurance of quality when the formulation reached full-scale production, as well as to maintain future assurance of product quality and stability. This topic will explore the use and general limitations of typical compendial USP apparatus, noncompendial modifications to the standard USP apparatus, and non-USP apparatus designed to yield small-volume dissolution methods with reliable results. in addition, related issues concerning apparatus calibration, method development, and method validation of the modified dissolution apparatus will be reviewed.