Alternative forms of levothyroxine replacement based on formulations with improved drug solubility

• Autor(a) principal: Barreira, António Francisco de Oliveira Gomes
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/160307
• topic: Sodium levothyroxine; API-ILS; bioavailability studies; biopolymers’aerogels; dry powders; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

A substantial portion of the population is affected by thyroid diseases such as hypo- thyroidism. Levothyroxine is therapeutically used to treat hypothyroidism and to suppress thyroid stimulating hormone secretion in other thyroid diseases. In this work, three types of formulations were performed, starting with the synthesis of API-ILs based levothyroxine [T4] as a means to enhance [T4] solubility. For this matter [Na][T4] was combined choline [Ch] and 1-(2-hydroxyethyl)-3-methylimidazolium [C2OHMIM] cations. These two prepared com- pounds and [Na][T4] drug were analyzed by proton and carbon NMR, ATR-FTIR, and ele- mental analysis. The serum, water and PBS solubilities of the API-ILs were compared to the [Na][T4] and for thermal analysis DSC studies were carried through. Permeability assays were performed, and an enhanced adsorption capacity was observed. Additionally, it was revealed by cytotoxicity assays that cellular viability in L929 cells was preserved. Having an higher solubility and a partition coefficient (Kd) slightly inferior to the one of levothyroxine sodium salt, the ionic levothyroxine formulation [T4][C2OHMIM] can be considered as a potential al- ternative to levothyroxine commercial formulations with a good bioavailability. The second approach consisted on synthesis of aerogel matrixes based in a mixture two biopolymers kappa-carrageenan-locust bean gum (60%/40%) functionalized with ionic liquid [EO- MIM][Br]. These biopolymers were characterized by SEM, ATR-FTIR, Nitrogen Adsorption- Desorption, DSC and TGA. A successful impregnation of the [Na][T4] drug and API-ILs syn- thesized into the aerogels with different ratios of functionalization (nf, 1:1, 1:6) was achieved. Finally, the third approach was the development of dry powder formulations, produced through Supercritical CO2-assisted Spray Drying and subsequently assessed in Andersen-Cas- cade Impactor to evaluate aerodynamic properties. Furthermore, release assays with the dry powder’s formulations were accomplished with [Na][T4]_DP presenting a faster release pro- file when compared to [Ch][T4]_DP.