Characterization of the In Vitro Drug Exchange Profile of a Modified-Release Parenteral Solution for Veterinary Use

Abstract

The release or exchange profile of an active pharmaceutical ingredient (API) from its carrier or formulation matrix is an important characteristic of a drug product, especially for that of a long-acting or modified-release formulation. The ability to measure this phenomenon in vitro assures that the product is manufactured using the intended quality of raw materials, including API and excipients, and that control of the overall compounding process is maintained. Developing and validating an in vitro drug exchange (IVDE) method that is capable of reproducibly demonstrating quality required addressing some fundamental challenges. Primarily, a suitable medium was identified to extract the API over a reasonable amount of time to generate a release profile, while also ensuring the API does not degrade in this medium during the exchange interval and brief storage prior to being assayed. Secondarily, a system and processes that can be used in a quality control (QC) laboratory setting to enable extraction, sampling, and quantitative measurement of the API exchanged from one medium (phase) into another was designed. The final challenge was the ability to differentiate high-quality drug product from others containing the same API in what could be a lesser quality, or perhaps even a completely different formulation. To meet the third objective, the method development strategy included comparison of the release profiles of the developmental product against numerous other formulations. These included a commercial product containing the same API in a different matrix, lab-scale batches containing the same API and excipients at variable concentrations, lab-scale batches containing similar or related excipients, and lab-scale batches containing degraded excipients. Statistical criteria were set to demonstrate that the method was capable of discriminating the IVDE profiles of the developmental formulation from all others. In addition, the same criteria were set for QC testing at release and real-time stability intervals to assure long-term quality of the drug product.

In Vitro Release Test Methods for Drug Formulations for Parenteral Applications

“…The guidance provided by formulation type in this article should also be considered for veterinary formulations. One recent example reported by Folger et al describes the work conducted for a veterinary drug product consisting of a lipophilic drug dissolved in a low-viscosity oily matrix (27). This work included the identification of a suitable medium, which dissolved the drug over time without degrading it, and the development of a system and methodology that could be used in the quality control lab and could discriminate a quality product from one that was formulated or processed incorrectly.…”

Meeting Report: USP Workshop on In Vitro Testing for Meeting Future Challenges for Veterinary Dosage Forms

“…The next case study was presented by Timothy Priddy (Boehringer-Ingelheim) whose article on characterizing the in vitro drug exchange profile of a modified-release parenteral solution for veterinary use appears in this issue of Dissolution Technologies (20).…”