Solubility Enhancement and Formulation of Mouth Dissolving Tablet of Clonazepam with Solid Dispersion Technology



Título del documento: Solubility Enhancement and Formulation of Mouth Dissolving Tablet of Clonazepam with Solid Dispersion Technology
Revista: Revista de ciencias farmaceuticas basica e aplicada
Base de datos: PERIÓDICA
Número de sistema: 000363792
ISSN: 1808-4532
Autores: 1
1
3
Instituciones: 1MAEER's Maharashtra Institute of Pharmacy, Department of Pharmaceutics, Maharashtra. India
2MAEER's Maharashtra Institute of Pharmacy, Department of Pharmaceutical Chemistry, Maharashtra. India
Año:
Periodo: Ene-Mar
Volumen: 33
Número: 1
Paginación: 83-94
País: Brasil
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Experimental
Resumen en inglés Clonazepam (CLZ) is an anticonvulsant benzodiazepine widely used in the treatment of epilepsy. CLZ is a BCS Class II drug and its bioavailability is thus dissolution limited. The objective of the present study was to prepare solid dispersions (SDs) of CLZ by various techniques, using the amphiphilic carrier Gelucire 50/13 in various proportions, to increase its water solubility. Drug-polymer interactions were investigated by Fourier-transform infrared (FTIR) and Ultra-Violet (UV) spectroscopy. The SDs were characterized physically by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). A phase solubility study was performed and the stability constant (Ks) was found to be 275.27, while the negative Gibbs free energy (ΔGotr) indicated spontaneous solubilization of the drug. The dissolution study showed that the SDs considerably enhanced the dissolution rate of the drug. The FTIR and UV spectra revealed no chemical incompatibility between the drug and Gelucire 50/13. XRD patterns and the DSC profiles indicated the CLZ was in the amorphous form, which explains the improved dissolution rate of the drug from its SDs. Finally, mouth dissolving tablets (MDTs) were prepared from the optimized batches (kneading method) of solid dispersion, using crospovidone and Doshion P544 resin as superdisintegrants. The tablets were characterized by in-vitro disintegration and dissolution tests. The study of the MDTs showed disintegration times in the range 32.0±0.85 to 20.0±1.30 sec and dissolution was faster than for the commercial preparation. In conclusion, this investigation demonstrated the potential of solid dispersions of a drug with Gelucire 50/13 for promoting the dissolution of the drug and contributed to the understanding of the effect of a superdisintegrant on mouth dissolving tablets containing a solid dispersion of a hydrophobic drug
Disciplinas: Química
Palabras clave: Química farmacéutica,
Clonazepam,
Gelucire 50/13,
Dispersión sólida,
Solubilidad,
Tabletas
Keyword: Chemistry,
Medicinal chemistry,
Clonazepam,
Gelucire 50/13,
Solid dispersion,
Solubility,
Tablets
Texto completo: Texto completo (Ver HTML)