Use of In silico Methodologies to Predict the Bioavailability of Oral Suspensions: A Regulatory Approach

Oral suspensions are heterogeneous disperse systems, and the particle size distribution, crystalline form of the dispersed solid, and composition of the formulation can be listed as parameters that control the drug dissolution rate and its bioavailability. The aim of this work was to develop a discr...

Full description

Saved in:

Bibliographic Details
Published in:	Current pharmaceutical design Vol. 29; no. 38; p. 3040
Main Authors:	da Silva Honório, Thiago, Simon, Alice, Machado, Raiane Monteiro Clacino, Rodrigues, Carlos Rangel, do Carmo, Flávia Almada, Cabral, Lucio Mendes, de Sousa, Valeria Pereira
Format:	Journal Article
Language:	English
Published:	United Arab Emirates 01-01-2023
Subjects:	Biological Availability Caco-2 Cells Humans Ibuprofen - chemistry Ibuprofen - pharmacokinetics Solubility Sulfonamides Suspensions Oral suspensions regulatory actions GastroPlusTM dissolution test in silico pharmacokinetics in vitro-in vivo correlation (IVIVC)
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Oral suspensions are heterogeneous disperse systems, and the particle size distribution, crystalline form of the dispersed solid, and composition of the formulation can be listed as parameters that control the drug dissolution rate and its bioavailability. The aim of this work was to develop a discriminative dissolution test, which, in association with in silico methodologies, can make it possible to safely anticipate bioavailability problems. Nimesulide and ibuprofen (BCS class II) and cephalexin (BCS class I) oral suspensions were studied. Previously, solid-state structure and particle size in active pharmaceutical ingredients were characterized and the impact of differences on solubility was evaluated for the choice of discriminative medium. Afterwards, particle size distribution (0.1 to 360 μm), dissolution profile, and permeability in Caco-2 cell of commercial suspensions, were determined. These parameters were used as input for the establishment of the correlation (IVIVC) for the suspensions using the GastroPlus™ with Wagner-Nelson and Loo- Riegelmann deconvolution approach. The predicted/observed pharmacokinetic model showed good correlation coefficients (r) of 0.960, 0.950, and 0.901, respectively. The IVIVC was established for one nimesulide and two ibuprofen suspensions with r between 0.956 and 0.932, and the percent prediction error (%PE) did not exceed 15%. In this work, we have performed a complete study combining approaches with the aim of anticipating the safety and efficacy of oral pharmaceutical suspensions in order to provide a regulatory tool for this category of products in a faster and more economical way.
ISSN:	1873-4286
DOI:	10.2174/0113816128257028231030113156