Adaptive perfusion: An in vitro release test (IVRT) for complex drug products. 2021

Deval Patel, and Ying Zhang, and Yixuan Dong, and Haiou Qu, and Darby Kozak, and Muhammad Ashraf, and Xiaoming Xu
Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA; Office of Quality Surveillance, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.

In this work, adaptive perfusion, a pressure-driven separation method based on the principle of tangential flow filtration (TFF) was developed for investigating the rate and extent of drug release from drug products containing particulates, such as emulsions, suspensions, liposomes, drug-protein complexes. The TFF filters were pre-conditioned with unique conditioning solutions and processes to improve the fiber reproducibility and robustness. The adaptive perfusion method achieved size-based separation of the particulates with simultaneous analysis of the released drug as well as remaining drug. By contrast to conventional dialysis methods, the adaptive perfusion method can be used to measure the rate and extent of the drug release from drug solution, drug loaded micelles and nanoemulsions via adjustment of the filter molecular weight cutoff, feed flow rate or back-pressure. Notably, the adaptive perfusion method provided discriminatory drug release profiles for drug in solution, in micelles, and in small, medium, and large globule size nanoemulsions. The drug release profile obtained using adaptive perfusion method was found significantly faster (e.g., minutes rather than hours) and higher (e.g., >60%) than the release obtained using dialysis method. The IVRT method presented here is free from the constraints of rate-limiting factors, such as diffusion through dialysis membrane, and has potential to be extended further to examine the impact of manufacturing process on drug distribution and release characteristics of other challenging complex drug products.

UI MeSH Term Description Entries
D010477 Perfusion Treatment process involving the injection of fluid into an organ or tissue. Perfusions
D004655 Emulsions Colloids formed by the combination of two immiscible liquids such as oil and water. Lipid-in-water emulsions are usually liquid, like milk or lotion. Water-in-lipid emulsions tend to be creams. The formation of emulsions may be aided by amphiphatic molecules that surround one component of the system to form MICELLES. Emulsion
D006435 Renal Dialysis Therapy for the insufficient cleansing of the BLOOD by the kidneys based on dialysis and including hemodialysis, PERITONEAL DIALYSIS, and HEMODIAFILTRATION. Dialysis, Extracorporeal,Dialysis, Renal,Extracorporeal Dialysis,Hemodialysis,Dialyses, Extracorporeal,Dialyses, Renal,Extracorporeal Dialyses,Hemodialyses,Renal Dialyses
D015203 Reproducibility of Results The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results. Reliability and Validity,Reliability of Result,Reproducibility Of Result,Reproducibility of Finding,Validity of Result,Validity of Results,Face Validity,Reliability (Epidemiology),Reliability of Results,Reproducibility of Findings,Test-Retest Reliability,Validity (Epidemiology),Finding Reproducibilities,Finding Reproducibility,Of Result, Reproducibility,Of Results, Reproducibility,Reliabilities, Test-Retest,Reliability, Test-Retest,Result Reliabilities,Result Reliability,Result Validities,Result Validity,Result, Reproducibility Of,Results, Reproducibility Of,Test Retest Reliability,Validity and Reliability,Validity, Face
D065546 Drug Liberation Release of drugs from DOSAGE FORMS into solution. Drug Dissolution,Drug Release,Dissolution, Drug,Liberation, Drug,Release, Drug

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