In Vitro–In Vivo Correlation of Efavirenz Tablets Using GastroPlus®
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The aim of the present work was to use GastroPlus™ software for the prediction of pharmacokinetic profiles and in vitro–in vivo correlation (IVIVC) as tools to optimize the development of new generic medications. GastroPlus™ was used to simulate the gastrointestinal compartment and was based on the advanced compartmental absorption and transit model. Powder dissolution and efavirenz tablet dissolution studies were carried out to generate data from which correlation was established. The simulated plasma profile, based on the physicochemical properties of efavirenz, was almost identical to that observed in vivo for biobatches A and B. A level A IVIVC was established for the dissolution method obtained for the generic candidate using the Wagner–Nelson (r 2 = 0.85) and for Loo–Riegelman models (r 2 = 0.92). The percentage of fraction absorbed indicated that 0.5% sodium lauryl sulfate may be considered a biorelevant dissolution medium for efavirenz tablets. The simulation of gastrointestinal bioavailability and IVIVC obtained from immediate-release tablet formulations suggests that GastroPlus™ is a valuable in silico method for IVIVC and for studies directed at developing formulations of class II drugs.
KEY WORDSbioavailability computational simulation efavirenz GastroPlus™ in vivo–in vitro correlation
This work was supported by FAPERJ, Edital CAPES Nanobiotecnologia 2008, and CNPq. We are grateful to Michelle Parvatiyar for her English review.
- 1.Food and Drug Administration. Guidance for industry: bioavailability and bioequivalence studies for orally administers drug products. General Considerations. US Department of Health and Human Services, CDER/FDA; 2003.Google Scholar
- 3.Food and Drug Administration. Guidance for industry: waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a Biopharmaceutics Classification System. US Department of Health and Human Services, CDER/FDA; 2000.Google Scholar
- 11.Simulations Plus, Manual GastroPlus™, California, EUA; 2010.Google Scholar
- 20.International Standard Organization. General requirements for the competence of the material producers. ISO Guide 34, 2009.Google Scholar
- 21.The United States Pharmacopoeia and National Formulary. 34th ed. Rockville, MD: USP Convention Inc.; 2011.Google Scholar
- 22.ICH, validation of analytical procedures: text and methodology (Q2R1), in International Conference on Harmonization; November 2005.Google Scholar
- 24.Brazilian Pharmacopoeia. 5th ed. Brazilian Health Surveillance Agency; 2010.Google Scholar
- 26.Mithani SD, Bakatselou V, TenHoor CN, Dressman JB. Estimation of the increase in solubility of drugs as a function of bile salt concentration. Pharm Res. 1996;10:164–7.Google Scholar
- 31.Rowel RC, Sheskey PJ, Quinn ME. Handbook of pharmaceutical excipients. 6th ed. London: Pharmaceutical Press; 2009.Google Scholar
- 32.Brown CK, Chokshi HP, Nickerson B, Reed RA, Rohrs BR, Shah PS. Acceptable analytical practices for dissolution testing of poorly soluble compounds. Pharm Technol. 2004;28:56–65.Google Scholar