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In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.
Biopharm Drug Dispos. 2012 Oct; 33(7):366-77.BD

Abstract

The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard.

Authors+Show Affiliations

College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22815122

Citation

Tsume, Yasuhiro, et al. "In Silico Prediction of Drug Dissolution and Absorption With Variation in Intestinal pH for BCS Class II Weak Acid Drugs: Ibuprofen and Ketoprofen." Biopharmaceutics & Drug Disposition, vol. 33, no. 7, 2012, pp. 366-77.
Tsume Y, Langguth P, Garcia-Arieta A, et al. In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen. Biopharm Drug Dispos. 2012;33(7):366-77.
Tsume, Y., Langguth, P., Garcia-Arieta, A., & Amidon, G. L. (2012). In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen. Biopharmaceutics & Drug Disposition, 33(7), 366-77. https://doi.org/10.1002/bdd.1800
Tsume Y, et al. In Silico Prediction of Drug Dissolution and Absorption With Variation in Intestinal pH for BCS Class II Weak Acid Drugs: Ibuprofen and Ketoprofen. Biopharm Drug Dispos. 2012;33(7):366-77. PubMed PMID: 22815122.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen. AU - Tsume,Yasuhiro, AU - Langguth,Peter, AU - Garcia-Arieta,Alfredo, AU - Amidon,Gordon L, Y1 - 2012/08/21/ PY - 2012/03/20/received PY - 2012/06/04/revised PY - 2012/07/03/accepted PY - 2012/7/21/entrez PY - 2012/7/21/pubmed PY - 2013/2/26/medline SP - 366 EP - 77 JF - Biopharmaceutics & drug disposition JO - Biopharm Drug Dispos VL - 33 IS - 7 N2 - The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. SN - 1099-081X UR - https://www.unboundmedicine.com/medline/citation/22815122/In_silico_prediction_of_drug_dissolution_and_absorption_with_variation_in_intestinal_pH_for_BCS_class_II_weak_acid_drugs:_ibuprofen_and_ketoprofen_ L2 - https://doi.org/10.1002/bdd.1800 DB - PRIME DP - Unbound Medicine ER -