Systematic evaluation of the impact of solid-state polymorphism on the bioavailability of thalidomide.

Autor: de Oliveira GHO; Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal de São João del-Rei - UFJS, Av. Sebastião Gonçalves Coelho 400, Chanadour, Divinópolis, MG CEP: 35501-296, Brazil., do Nascimento SB; Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal de São João del-Rei - UFJS, Av. Sebastião Gonçalves Coelho 400, Chanadour, Divinópolis, MG CEP: 35501-296, Brazil., de Oliveira FM; Programa de Pós-graduação em Ciências da Saúde, Universidade Federal de São João del-Rei - UFJS, Av. Sebastião Gonçalves Coelho 400, Chanadour, Divinópolis, MG CEP: 35501-296, Brazil., Belo VS; Programa de Pós-graduação em Ciências da Saúde, Universidade Federal de São João del-Rei - UFJS, Av. Sebastião Gonçalves Coelho 400, Chanadour, Divinópolis, MG CEP: 35501-296, Brazil., de Alencar Danda LJ; Núcleo Controle de Qualidade de Medicamentos e Correlatos - NCQMC, Universidade Federal de Pernambuco - UFPE, Av. Artur de Sá, S/N. Cidade Universitária, Recife, PE CEP: 50740-520, Brazil., Soares-Sobrinho JL; Núcleo Controle de Qualidade de Medicamentos e Correlatos - NCQMC, Universidade Federal de Pernambuco - UFPE, Av. Artur de Sá, S/N. Cidade Universitária, Recife, PE CEP: 50740-520, Brazil., Fialho SL; Pharmaceutical Research and Development, Ezequiel Dias Foundation, Rua Conde Pereira Carneiro, 80, Gameleira, Belo Horizonte, MG CEP: 30510-010, Brazil., Bedor DCG; Núcleo de Desenvolvimento Farmacêutico e Cosmético - NUDFAC, Universidade Federal de Pernambuco, Av. Artur de Sá, S/N. Cidade Universitária, Recife, PE CEP: 50740-520, Brazil., de Castro WV; Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal de São João del-Rei - UFJS, Av. Sebastião Gonçalves Coelho 400, Chanadour, Divinópolis, MG CEP: 35501-296, Brazil. Electronic address: whocely@ufsj.edu.br.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2019 Aug 01; Vol. 136, pp. 104937. Date of Electronic Publication: 2019 May 23.
DOI: 10.1016/j.ejps.2019.05.015
Abstrakt: Thalidomide (TLD) is used to treat erythema nodosum leprosum (ENL), multiple myeloma, aphthous ulceration and wasting syndrome in HIV patients. The API can be found in two crystalline habits known as α-TLD and β-TLD. The saturation solubility (C s ) and the dissolution profiles under non-sink and sink conditions of both polymorphs were assessed. In addition, mini-capsules containing α-TLD or β-TLD without excipients were orally given (10 mg/kg) to Wistar rats. An intravenous (i.v.) dose was also administrated (5 mg/kg). The C s values for α-TLD and β-TLD were not significantly different (α = 56.2 ± 0.5 μg·mL -1 ; β = 55.2 ± 0.2 μg·mL -1 ). However, the dissolution profile of α-TLD presented the fastest rate and the largest extension of drug dissolution than that from β-TLD (80% in 4 h versus 55% in 4 h). The α-TLD provided a more favorable pharmacokinetic than the β-TLD (maximum plasma concentration - C max : 5.4 ± 0.90 μg·mL -1 versus 2.6 ± 0.2 μg·mL -1 ; area under the curve of the concentration-time profile from time zero to infinity - AUC 0-∞ : 44.3 ± 8.8 μg·h·mL -1 versus 33.9 ± 4.7 μg·h·mL -1 ; absolute bioavailability - F: 92.2 ± 18.5% versus 70.5 ± 9.9%, respectively). Drug suppliers and pharmaceutical companies should strictly control the technological processes involved in the TLD API synthesis as well as in the production of the pharmaceutical dosage form in order to guarantee the inter-batch homogeneity and therefore, product compliance.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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