Description:
Dissolution is critical for absorption and bioavailability, and for product quality assessments during drug product life cycle. Dissolution methods predictive of in vivo drug performance enable linking the drug product quality to its use in the patient/consumer. The objective of this effort is to evaluate a novel dissolution system developed by Rohm and Haas based on a series solids transfer approach which incorporates drug pharmacokinetic characteristics to simulate a biomimetic system. The Rohm and Haas three chamber dissolution system in which the media pH, flow rates and volumes of simulated gastric and intestinal fluids can be independently controlled, was used to study products classified according to the Biopharmaceutics Classification System (BCS). The publicly available plasma drug concentration-time profiles of eight selected products (propranolol, bupropion, ibuprofen, metformin, acetaminophen, azithromycin, doxycycline and furosemide), representing all four BCS classes, and their release profiles simulated utilizing the Rohm and Haas system were explored to determine the suitability and the feasibility of this system to mimic in vivo drug plasma concentration-time profiles and also, distinguish among oral dosage forms that have immediate and extended release characteristics.
This presentation will describe our current efforts focusing on assessment of the Rohm and Haas system utilizing the above representative drugs.
The following observations were made:
1) Overall, the Rohm and Haas system could simulate in vivo drug concentration-time profiles for the test dosage forms that were consistent with the profiles used to develop the system algorithm.
2) The deviations observed, albeit limited, may be explained by differences in drug solubility and/or release characteristics.
These exploratory efforts warrant further evaluation of the Rohm and Haas in vitro system as it provides a unique approach in characterizing in vivo dissolution of drug products.
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Author
Dr. Lucinda F. Buhse
Director, Food and Drug Administration, Division of Pharmaceutical Analysis, OTR/OPS/CDER/FDA |
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Author
Elsbeth G. Chikhale
Food and Drug Administration, Office of New Drug Quality Assessment, OPS/CDER |
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Author
Swapan K. De
Food and Drug Administration, Office of New Drug Quality Assessment, OPS/CDER |
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Author
Dr. William H. Doub
Lead Chemist, R&D, Food and Drug Administration, Division of Pharmaceutical Analysis, OTR/OPS/CDER/FDA |
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Author
Dr. Zongming Gao
Research Scientist, Food and Drug Administration, Division of Pharmaceutical Analysis, OTR/OPS/CDER/FDA |
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Author
Robert (Donghao) Lu
Food and Drug Administration, Office of New Drug Quality Assessment, OPS/CDER |
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Author
Mr. Houda Mahayni
Regulatory Review Officer, Food and Drug Administration, Office of New Drug Quality Assessment, OPS/CDER |
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Author
Mr. Pramoda K. Maturu
Food and Drug Administration, Office of New Drug Quality Assessment, OPS/CDER |
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Author
Tarun D. Mehta
Food and Drug Administration, Office of New Drug Quality Assessment, OPS/CDER |
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Author
Dr. Arzu Selen
Associate Director, Food and Drug Administration, Office of New Drug Quality Assessment, OPS/CDER |
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