| Texto completo | |
| Autor(es): |
Nascimento, A. L. C. S.
;
Martins, I. C. B.
;
Sposito, L.
;
Morais-Silva, G.
;
Duarte, J. L.
;
Rades, T.
;
Chorilli, M.
Número total de Autores: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | International Journal of Pharmaceutics; v. 653, p. 11-pg., 2024-02-08. |
| Resumo | |
Multidrug therapeutic hybrids constitute a promising proposal to overcome problems associated with traditional formulations containing physical mixtures of drugs, potentially improving pharmacological and pharmaceutical performance. Indomethacin (IND) is a non -selective non -steroidal anti-inflammatory drug (NSAIDs) that acts by inhibiting normal processes of homeostasis, causing a series of side effects, such as gastrointestinal symptoms. Proton pump inhibitors, such as omeprazole (OME), have been used to treat such gastrointestinal tract symptoms. In this work, two new multidrug therapeutic hybrids were prepared (an IND:OME salt and an IND:OME coamorphous system) by ball mill grinding crystalline IND and OME under different conditions, i.e., liquid assisted grinding (LAG) with ethanol and dry grinding, respectively. The crystalline salt returned to a neutral state coamorphous system when submitted to ball mill grinding in the absence of solvent (dry grinding), but the reverse process (LAG of the IND:OME co -amorphous system) showed partial decomposition of OME. The IND: OME co -amorphous system showed a higher physical stability than the neat IND and OME amorphous materials (with an amorphous stability longer than 100 days, compared to 4 and 16 h for the neat amorphous drugs, respectively, when stored at dry conditions at room temperature). Furthermore, OME presented a higher chemical stability in solution when dissolved from a salt form than from the pure crystalline form. The dissolution studies showed a dissolution enhancement for IND in both salt (1.8 -fold after 8 h of dissolution) and coamorphous (2.5 -fold after 8 h of dissolution) forms. Anti-inflammatory activity using a mice paw oedema model showed an increase of the pharmacological response to IND at a lower dose (similar to 5mg/kg) for both IND:OME salt (2.8 -fold) and IND:OME co -amorphous system (3.2 -fold) after 6 h, when compared to the positive control group (IND, administered at 10 mg/kg). Additionally, the anti-inflammatory activity of both salt and co -amorphous form was faster than for the crystalline IND. Finally, an indomethacin-induced gastric ulceration assay in mice resulted in a higher mucosal protection at the same dose (40 mg/kg) for both IND:OME salt and IND:OME coamorphous system when compared with crystalline OME. (AU) | |
| Processo FAPESP: | 18/23357-5 - Cocristais multicomponentes de Anti-Inflamatórios Não Esteróides (AINEs) e Inibidores de Bomba de Prótons (IBPs): desenvolvimento, caracterização e avaliação biológica in vitro e in vivo |
| Beneficiário: | André Luiz Carneiro Soares do Nascimento |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 21/08289-6 - Novas formas sólidas de AINEs e IBPs: desenvolvimento, caracterização e avaliação biológica in vitro e in vivo |
| Beneficiário: | André Luiz Carneiro Soares do Nascimento |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado |