Tags

Type your tag names separated by a space and hit enter

An In Vitro Dissolution Method for Testing Extended-Release Tablets Under Mechanical Compression and Sample Friction.
J Pharm Sci. 2022 06; 111(6):1652-1658.JP

Abstract

The release and dissolution of an active pharmaceutical ingredient (API) from the solid oral formulation into the gastrointestinal (GI) tract is critical for the drug's absorption into systemic circulation. Extended-release (ER) solid oral dosage forms are normally subjected to physical shear and grinding forces as well as pressure exerted by peristaltic movements when passing through the GI tract. The complex physical contraction and sample friction exerted by the GI tract are not simulated well by compendial dissolution methods. These limitations render traditional in vitro dissolution testing unable to discriminate and predict a product's in vivo performance. The objective of this study was to develop a dissolution method that better simulates the GI environment that products are subject to when taken by patients. A newly designed Mechanical Apparatus under GI Conditions (MAGIC) was assembled with a dissolution platform and mechanical capabilities to allow in vitro dissolution testing under sample contractions and friction. The dissolution platform, with medium flow-through configuration, was manufactured by 3D printing. A 60 mg polymer matrix-based ER nifedipine product was tested. To simulate GI physiological conditions during the dissolution testing, the flow rate of the medium, and a combination of mechanical compression with rotation induced sample friction at various rotation frequencies were explored. The polymer matrix-based nifedipine ER formulation used here failed its controlled release functionality in the simulated GI environment under mechanical compression and sample friction. The results showed that the MAGIC system, with flow-through configuration under compression and sample friction, has advantages over compendial methods in testing ER solid oral formulations.

Authors+Show Affiliations

US Food and Drug Administration, Center for Drug Evaluation and Research, Division of Complex Drug Analysis, St. Louis, MO, 63110. Electronic address: zongming.gao@fda.hhs.gov.US Food and Drug Administration, Center for Drug Evaluation and Research, Division of Complex Drug Analysis, St. Louis, MO, 63110.US Food and Drug Administration, Center for Drug Evaluation and Research, Division of Complex Drug Analysis, St. Louis, MO, 63110.US Food and Drug Administration, Center for Drug Evaluation and Research, Division of Complex Drug Analysis, St. Louis, MO, 63110.US Food and Drug Administration, Center for Drug Evaluation and Research, Division of Complex Drug Analysis, St. Louis, MO, 63110.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34742730

Citation

Gao, Zongming, et al. "An in Vitro Dissolution Method for Testing Extended-Release Tablets Under Mechanical Compression and Sample Friction." Journal of Pharmaceutical Sciences, vol. 111, no. 6, 2022, pp. 1652-1658.
Gao Z, Cao LNY, Liu X, et al. An In Vitro Dissolution Method for Testing Extended-Release Tablets Under Mechanical Compression and Sample Friction. J Pharm Sci. 2022;111(6):1652-1658.
Gao, Z., Cao, L. N. Y., Liu, X., Tian, L., & Rodriguez, J. D. (2022). An In Vitro Dissolution Method for Testing Extended-Release Tablets Under Mechanical Compression and Sample Friction. Journal of Pharmaceutical Sciences, 111(6), 1652-1658. https://doi.org/10.1016/j.xphs.2021.10.036
Gao Z, et al. An in Vitro Dissolution Method for Testing Extended-Release Tablets Under Mechanical Compression and Sample Friction. J Pharm Sci. 2022;111(6):1652-1658. PubMed PMID: 34742730.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An In Vitro Dissolution Method for Testing Extended-Release Tablets Under Mechanical Compression and Sample Friction. AU - Gao,Zongming, AU - Cao,Leo N Y, AU - Liu,Xiaofei, AU - Tian,Li, AU - Rodriguez,Jason D, Y1 - 2021/11/04/ PY - 2021/06/23/received PY - 2021/10/29/revised PY - 2021/10/29/accepted PY - 2021/11/8/pubmed PY - 2022/5/25/medline PY - 2021/11/7/entrez KW - Critical quality attributes (CQAs) KW - Extended-release (ER) KW - Gastrointestinal (GI) condition KW - In vitro dissolution testing KW - Mechanical apparatus under GI condition (MAGIC) system KW - Medium flow-through configuration KW - Simulated GI compression and friction SP - 1652 EP - 1658 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 111 IS - 6 N2 - The release and dissolution of an active pharmaceutical ingredient (API) from the solid oral formulation into the gastrointestinal (GI) tract is critical for the drug's absorption into systemic circulation. Extended-release (ER) solid oral dosage forms are normally subjected to physical shear and grinding forces as well as pressure exerted by peristaltic movements when passing through the GI tract. The complex physical contraction and sample friction exerted by the GI tract are not simulated well by compendial dissolution methods. These limitations render traditional in vitro dissolution testing unable to discriminate and predict a product's in vivo performance. The objective of this study was to develop a dissolution method that better simulates the GI environment that products are subject to when taken by patients. A newly designed Mechanical Apparatus under GI Conditions (MAGIC) was assembled with a dissolution platform and mechanical capabilities to allow in vitro dissolution testing under sample contractions and friction. The dissolution platform, with medium flow-through configuration, was manufactured by 3D printing. A 60 mg polymer matrix-based ER nifedipine product was tested. To simulate GI physiological conditions during the dissolution testing, the flow rate of the medium, and a combination of mechanical compression with rotation induced sample friction at various rotation frequencies were explored. The polymer matrix-based nifedipine ER formulation used here failed its controlled release functionality in the simulated GI environment under mechanical compression and sample friction. The results showed that the MAGIC system, with flow-through configuration under compression and sample friction, has advantages over compendial methods in testing ER solid oral formulations. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/34742730/An_In_Vitro_Dissolution_Method_for_Testing_Extended_Release_Tablets_Under_Mechanical_Compression_and_Sample_Friction_ DB - PRIME DP - Unbound Medicine ER -