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Evaluation of testosterone compatibility with different excipients for the development of a self-emulsifying drug delivery system

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Abstract

Testosterone is a cholesterol-derived steroidal hormone responsible for male sexual characteristics. Besides undergoing intense hepatic and intestinal metabolism, it presents low aqueous solubility and low intestinal permeability. Various strategies have been investigated to improve the bioavailability of poorly water-soluble such as testosterone, including the use of lipid systems. The main goal of this work was to carry out a pre-formulation study for the development a liquid self-emulsifying drug delivery system (L-SEDDS) with testosterone. The compatibility of the drug with oils and surfactants was investigated using DSC, TG, FTIR and isothermal stress test (IST). Interactions with testosterone were identified for oleic acid, Span 80 and Castor oil, in which greater changes were observed in the DSC and DTG thermal profiles. The incompatibility of the testosterone with these excipients was confirmed by the IST after 15 or 30 days of storage at 50 °C. A phase diagram was constructed using different proportions (w/w) of Captex 355, Tween 80 and Span 85. Formulations were characterized for size, PdI and zeta potential. F4 showed the highest zeta potential values (− 30.70 ± 2.28 mV and − 33.25 ± 1.77 mV) and lowest PdI values (0.232 ± 0.001 and 0.244 ± 0.011) (before and after drug incorporation, respectively). The pre-formulation studies enabled a rational selection of excipients for the development of L-SEDDS containing testosterone, thus reinforcing the importance and applicability of analytical and thermo-analytical techniques in the development of new formulations.

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Acknowledgements

This work was financially supported by the following Brazilian research funding agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Financiadora de Estudos e Pesquisas (FINEP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES – Finance code 001).

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Authors and Affiliations

  1. Centro de Pesquisa, Desenvolvimento Tecnológico e Inovação em Fármacos, Medicamentos e Cosméticos (FarmaTec), Universidade Federal de Goiás, Goiânia, GO, Brazil

    Bárbara Cristina Campos Ribeiro, Emilio Ramos Cintra, Eliana Martins Lima, Luís Antônio Dantas Silva & Danielle Guimarães Almeida Diniz

  2. Alameda Flamboyant, Quadra K, Edifício LIFE Parque Tecnológico Samambaia Campus Universitário UFG, Goiânia, GO, CEP 74690-631, Brazil

    Danielle Guimarães Almeida Diniz

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  1. Bárbara Cristina Campos Ribeiro
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Bárbara Cristina Campos Ribeiro and Emilio Ramos Cintra. The first draft of the manuscript was written by Luís Antônio Dantas Silva and Danielle Guimarães Almeida Diniz. Resources and funding supporte by Eliana Martins Lima. All authors commented on previous versions of the manuscript and approved the final manuscript.

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Correspondence to Danielle Guimarães Almeida Diniz.

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Ribeiro, B.C.C., Cintra, E.R., Lima, E.M. et al. Evaluation of testosterone compatibility with different excipients for the development of a self-emulsifying drug delivery system. J Therm Anal Calorim 148, 159–168 (2023). https://doi.org/10.1007/s10973-022-11751-4

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