RESUMEN

Hot-melt extrusion (HME) has gained increasing attention in the pharmaceutical industry; however, its potential in the preparation of solid self-emulsifying drug delivery systems (S-SMEDDS) is still unexplored. This study sought to prepare enteric S-SMEDDS by HME and evaluate the effects of the process and formulation variables on S-SMEDDS properties via Box-Behnken design. Liquid SMEDDS were developed, and carvedilol was used as a class II model drug. Mean size, polydispersity index (PdI) and zeta potential of the resulting microemulsions were determined. The extrudates were then obtained by blending the lipid mixture and HPMCAS using a twin-screw hot-melt extruder. SEM, optical microscopy and PXRD were used to characterize the extrudates. In vitro microemulsion reconstitution and drug release were also studied. L-SMEDDS gave rise to microemulsions with low mean size, PdI and zeta potential (140.04 ±â€¯7.22 nm, 0.219 ±â€¯0.011 and -9.77 ±â€¯0.86 mV). S-SMEDDS were successfully prepared by HME, and an HMPCAS matrix was able to avoid microemulsion reconstitution and retain drug release in pH 1.2 (12.97%-25.54%). Conversely, microemulsion reconstitution and drug release were gradual in pH 6.8 and complete for some formulations. Extrudates prepared at the lowest drug concentration and highest temperature and recirculation time promoted a complete and rapid drug release in pH 6.8 giving rise to small and uniform microemulsion droplets.

Asunto(s)

Química Farmacéutica/métodos , Sistemas de Liberación de Medicamentos , Emulsiones/química , Carbazoles/administración & dosificación , Carbazoles/farmacocinética , Carvedilol , Química Farmacéutica/instrumentación , Liberación de Fármacos , Calor , Concentración de Iones de Hidrógeno , Lípidos/química , Metilcelulosa/análogos & derivados , Metilcelulosa/química , Tamaño de la Partícula , Propanolaminas/administración & dosificación , Propanolaminas/farmacocinética , Solubilidad

RESUMEN

OBJECTIVES: This study sought to evaluate the achievement of carvedilol (CARV) inclusion complexes with modified cyclodextrins (HPßCD and HPγCD) using fluid-bed granulation (FB). METHODS: The solid complexes were produced using FB and spray drying (SD) and were characterised by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction, SEM, flowability and particle size analyses and in vitro dissolution. KEY FINDINGS: The DSC, FTIR and powder X-ray diffraction findings suggested successful CARV inclusion in the modified ß- and γ-cyclodextrins, which was more evident in acidic media. The CARV dissolution rate was ~7-fold higher for complexes with both cyclodextrins prepared using SD than for raw CARV. Complexes prepared with HPßCD using FB also resulted in a significant improvement in dissolution rate (~5-fold) and presented superior flowability and larger particle size. CONCLUSIONS: The findings suggested that FB is the best alternative for large-scale production of solid dosage forms containing CARV. Additionally, the results suggest that HPγCD could be considered as another option for CARV complexation because of its excellent performance in inclusion complex formation in the solid state.

Asunto(s)

Carbazoles/química , Propanolaminas/química , beta-Ciclodextrinas/química , gamma-Ciclodextrinas/química , Rastreo Diferencial de Calorimetría/métodos , Carvedilol , Composición de Medicamentos/métodos , Tamaño de la Partícula , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Difracción de Rayos X/métodos