ABSTRACT
ABSTRACT Different solid forms of an active pharmaceutical ingredient can have distinct chemical and physical characteristics. In this work, we studied the solubility and dissolution properties of the described tibolone polymorphic forms (I and II). Both forms were successively recrystallized and characterized by powder X-ray diffraction and attenuated total reflection infrared spectroscopy. Equilibrium solubility and dissolution profiles were performed for both forms. Solubility studies demonstrated that form II is statistically more soluble in water, 0.01 mol L-1 HCl and pH 4.5 acetate buffer. The solubility of forms I and II were explained in terms of crystal packing. Dissolution tests of tablets showed a lower release of polymorphic form II than form I from tablets. The results showed an impact of polymorphism on the quality of tibolone tablets and suggest that tibolone forms I and II can show distinct interactions with pharmaceutical excipients used in tablets. Therefore, only form I is acceptable for the preparation of tablet forms. Based on our results, we propose the quality control on tibolone raw materials using X-ray diffraction analysis and attenuated total reflection infrared spectroscopy.
Subject(s)
Solubility/drug effects , Dissolution/analysis , Spectrum Analysis , Tablets/standards , X-Ray Diffraction/methods , Pharmaceutical Preparations/standardsABSTRACT
A ineficácia clínica de muitos medicamentos tem servido de alerta para estudos mais profundos sobre os componentes da formulação, processos empregados e características físico-químicas dos fármacos. O objetivo deste trabalho foi avaliar a liberação in vitro de comprimidos de fosfato de primaquina disponíveis no Brasil para tratamento da malária, e o desenvolvimento de novas formulações de liberação convencional. Embora os comprimidos de fosfato de primaquina estudados tenham sido aprovados pelos critérios propostos pela Farmacopéia Americana (2006) para o teste de dissolução, não apresentaram desempenho adequado para o perfil de dissolução, mostrando retenção do fármaco durante a liberação. Os resultados indicam a existência de problemas nos comprimidos de fosfato de primaquina analisados, podendo sugerir como um dos fatores responsáveis pelo aparecimento de resistência dos parasitas.
The clinical inefficacy of many medications has served to highlight the need for deeper studies on the formulation components, processes used and physicochemical characteristics of drugs. The objective of this study was to evaluate the in vitro release of primaquine phosphate from tablets available in Brazil for treating malaria, and the development of new formulations for conventional release. Although the primaquine phosphate tablets studied had been approved according to the criteria proposed by the United States Pharmacopoeia (2006) for the dissolution test, they did not present adequate dissolution performance characteristics, in that there was drug retention during the release process. The results indicate the existence of problems in the primaquine phosphate tablets analyzed, and it may suggest that this is one of the factors responsible for the appearance of parasite resistance.
Subject(s)
Humans , Antimalarials/chemistry , Primaquine/chemistry , Area Under Curve , Antimalarials/standards , Brazil , Calorimetry, Differential Scanning , Malaria/drug therapy , Primaquine/standards , Reference Standards , Solubility , Tablets/chemistry , Tablets/standardsABSTRACT
Se realizó un estudio de estabilidad de las tabletas de griseofluvin 125 mg por los métodos de estabilidad acelerada y por vida de estante, con el empleo de la cromatografía líquida de alta resolución como método específico. Se analizó el efecto de la humedad sobre la estabilidad del producto, colocándose en hidrostatos con humedades controladas. Este medicamento de producción nacional cumplió con las especificaciones de calidad descriptivas en la USP XXII. Se comprobó la estabilidd física y química de la formulación durante 36 meses