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By: Xujin Lu

Xujin LuWhile dissolution testing is considered one of the most important in-vitro tests for pharmaceutical products, there continues to be gaps among many practitioners in understanding its role and the correct execution of testing. There are multiple reasons for the continued existence of these knowledge gaps, including a lack of systematic training on dissolution testing in college education courses, fewer new graduate students entering the pharmaceutical industry with training in the fundamentals of dissolution, and the continual need for scientists to refresh their dissolution skills and learn the new requirements in pharmacopeia and regulatory guidances related to in-vitro dissolution testing and applications. To address these issues, the AAPS In Vitro Release and Dissolution Testing focus group has developed an ecourse to provide a detailed review of the fundamentals and latest approaches and tools used in in-vitro dissolution testing for solid oral dosage forms.

In-vitro release and dissolution testing plays a vital role in several areas during drug development, including formulation design, drug delivery optimization, stability studies, and manufacturing quality control. Dissolution can be affected by drug substance factors (solubility, permeability, dissolution rate), dosage form factors (formulation design, composition and manufacturing processes), as well as the methods used for its assessment (apparatus, method, dissolution medium). This ecourse starts with a discussion of the Biopharmaceutics Classification System (BCS) classification of drug substances and then steps through the fundamentals of in-vitro release and dissolution testing. Dissolution is often a regulated analysis, and compliance with good manufacturing practices is mandatory for quality control of the drug products and stability studies. Adherence to the monographs in pharmacopeias is also expected. When addressing method development and validation issues, this ecourse emphasizes that many variables and uncertainties need to be evaluated during method development: (a) the physiochemical properties of the drug substance and the formulation characteristics; (b) the media selection; (c) the choice of apparatus and operation parameters; and (d) the sampling and sample analysis. Regulatory expectations, throughout method validation, including assessment of method variability, rationale for use of surfactants, justification of the use of atypical apparatus and agitation, demonstration of appropriate discriminatory power, and understanding of Critical Quality Attributes, are also presented.

Dissolution testing is a performance test as well. The in vitro dissolution data can be used for prediction of in-vivo performance, which has been an important application in pharmaceutical development. This ecourse contains modules for introduction of in-vitro in-vivo correlation (IVIVC) related topics. For examples, (1) the regulatory requirement of dissolution testing to capture clinically relevant product attributes; (2) the replacement of dissolution test by disintegration testing when specific criteria are met; (3) the discriminating ability in regard to a drug product bioavailability and bioequivalence; and (4) the acceptance of in-vitro dissolution testing in some situations as a reliable surrogate for biowaivers in drug product lifecycle management and generic product development. Importantly, this ecourse addresses how a dissolution test can be “predictive,” and when and how IVIVC can be developed.

Dissolution for Solid Oral Dosage Formulations consists of 12 lectures to fill knowledge gaps and present related fundamentals. All lectures are prepared and presented by academic and industrial experts in the field of in-vitro drug release and dissolution. The organizing team is confident that dissolution analysts and scientists involved with the development of solid oral dose formulations will benefit from taking this ecourse. We also look forward to feedback to help with developing new lectures on special topics related to in-vitro dissolution to meet further needs.

Xujin Lu, Ph.D., is a Senior Principal Scientist at Bristol-Myers Squibb Company.  Lu was the chair of the AAPS In Vitro Release and Dissolution Testing Focus Group from 2013 -2015, and is a current member of the Editorial Advisory Board of Dissolution Technologies.