Integrating biopharmaceutics risk assessment and in vivo absorption model in formulation development of BCS class I drug using the QbD approach
| Autor: | Sun K. Kim, Naseem A. Charoo, Rodrigo Cristofoletti |
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| Rok vydání: | 2017 |
| Předmět: |
Drug
Computer science Chemistry Pharmaceutical media_common.quotation_subject Pharmaceutical Science 02 engineering and technology Pharmacology Models Biological Risk Assessment 030226 pharmacology & pharmacy Intestinal absorption Quality by Design Biopharmaceutics 03 medical and health sciences 0302 clinical medicine Generic drug Drug Discovery Drugs Generic Humans Fluconazole media_common Active ingredient Organic Chemistry 021001 nanoscience & nanotechnology Intestinal Absorption Solubility Biochemical engineering 0210 nano-technology Critical quality attributes Risk assessment |
| Zdroj: | Drug Development and Industrial Pharmacy. 43:668-677 |
| ISSN: | 1520-5762 0363-9045 |
| DOI: | 10.1080/03639045.2016.1278013 |
| Popis: | Clinically relevant critical quality attributes (CQA's) were identified for the development of generic drug products containing fluconazole and potential design spaces relevant to the clinical application of the drug candidate was explored.A simplified scoring system for the biopharmaceutics risk assessment roadmap (BioRAM) is proposed to guide product development.Factorial design of experiments was employed to study the effect of formulation and process variables on CQA's. The in vivo model was developed for predicting the fraction of drug absorbed and to identify the effect of formulation components on drug absorption.BioRAM yielded low scores for fluconazole absorption with respect to severity (risks of sub and supra-bioavailable drug products), probability of incidence of bioinequivalent results and capacity of detection. The results demonstrated that dissolution was highly influenced by the active pharmaceutical ingredient (API) polymorphism and the ratio of diluents. Process variables (mixing time, lubricant concentration, lubrication time and filling speed) did not impact the clinical outcome of the formulation with respect to dissolution and content uniformity.Understanding the clinical implications of the adopted formulation approach led to the construction of purposeful design space and control strategy. |
| Databáze: | OpenAIRE |
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