Next Article in Journal
Developing Body-Components-Based Theranostic Nanoparticles for Targeting Ovarian Cancer
Next Article in Special Issue
In Vitro–In Vivo Correlations Based on In Vitro Dissolution of Parent Drug Diltiazem and Pharmacokinetics of Its Metabolite
Previous Article in Journal
Chitosan-Based Hydrogels Embedded with Hyaluronic Acid Complex Nanoparticles for Controlled Delivery of Bone Morphogenetic Protein-2
Previous Article in Special Issue
An In Vitro Study of the Influence of Curcuma longa Extracts on the Microbiota Modulation Process, In Patients with Hypertension
Open AccessArticle

In Silico Prediction of Plasma Concentrations of Fluconazole Capsules with Different Dissolution Profiles and Bioequivalence Study Using Population Simulation

1
Department of Pharmacy, Faculty of Pharmaceutical Sciences, Universidade de São Paulo—USP, Av. Prof. Lineu Prestes, 580, São Paulo—SP 05508-000, Brazil
2
Department of Pharmaceutical Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Universidade Federal de São Paulo—UNIFESP, Rua São Nicolau, 210, Centro, Diadema—SP 09913-030, Brazil
3
Faculty of Pharmacy & Pharmaceutical Sciences, Katz Group-Rexall Centre for Pharmacy & Health Research, University of Alberta, 11361 – 87 Avenue, Edmonton, AB T6G 2E1, Canada
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(5), 215; https://doi.org/10.3390/pharmaceutics11050215
Received: 26 February 2019 / Revised: 25 March 2019 / Accepted: 29 March 2019 / Published: 5 May 2019
A biowaiver is accepted by the Brazilian Health Surveillance Agency (ANVISA) for immediate-release solid oral products containing Biopharmaceutics Classification System (BCS) class I drugs showing rapid drug dissolution. This study aimed to simulate plasma concentrations of fluconazole capsules with different dissolution profiles and run population simulation to evaluate their bioequivalence. The dissolution profiles of two batches of the reference product Zoltec® 150 mg capsules, A1 and A2, and two batches of other products (B1 and B2; C1 and C2), as well as plasma concentration–time data of the reference product from the literature, were used for the simulations. Although products C1 and C2 had drug dissolutions < 85% in 30 min at 0.1 M HCl, simulation results demonstrated that these products would show the same in vivo performance as products A1, A2, B1, and B2. Population simulation results of the ln-transformed 90% confidence interval for the ratio of Cmax and AUC0–t values for all products were within the 80–125% interval, showing to be bioequivalent. Thus, even though the in vitro dissolution behavior of products C1 and C2 was not equivalent to a rapid dissolution profile, the computer simulations proved to be an important tool to show the possibility of bioequivalence for these products. View Full-Text
Keywords: fluconazole; biowaiver; dissolution; Biopharmaceutics Classification System (BCS); bioequivalence; GastroPlus fluconazole; biowaiver; dissolution; Biopharmaceutics Classification System (BCS); bioequivalence; GastroPlus
Show Figures

Graphical abstract

MDPI and ACS Style

Duque, M.D.; Silva, D.A.; Issa, M.G.; Porta, V.; Löbenberg, R.; Ferraz, H.G. In Silico Prediction of Plasma Concentrations of Fluconazole Capsules with Different Dissolution Profiles and Bioequivalence Study Using Population Simulation. Pharmaceutics 2019, 11, 215.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop