RESUMO

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 (?Gotr) 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.

Assuntos

Clonazepam , Composição de Medicamentos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Solubilidade , Comprimidos

RESUMO

The selection of a suitable superdisintegrant for a rapidly disintegrating dosage form is of the utmost importance, since disintegration time (DT) is a critical parameter. An experimental design was implemented, to find out the effects of superdisintegrants (sodium starch glycolate, crospovidone, croscarmellose sodium and methacrylic copolymer with divinyl benzene), at 2, 4, 6% w/w, on tablet hardness, with respect to DT. Methacrylic copolymer with divinyl benzene (at 4 wt%) was selected as the best superdisintegrant, adequate for the formulation of dispersible Tramadol tablets. With increasing hardness, there was a considerable increase in DT at all concentrations of superdisintegrants. A combination of crospovidone and methacrylic copolymer with divinyl benzene showed a remarkable drop in DT to 0.33 min. The stability of the batch with lowest DT was also tested under various conditions and the results suggested that there was no degradation over the test period.