SOLUBILITY ENHANCEMENT OF CARBAMAZEPINE USING LYOPHILIZED SOLID DISPERSION TECHNIQUE FOR ORAL ADMINISTRATION OF CAPSULES

Mulchand Shende*, Yogesh Gavhane and Pradeep Mundkar

ABSTRACT

Carbamazepine (CBZ) belongs to BCS Class-II used to control some types of seizures in the treatment of epilepsy and neuropathic pain by blocking use-dependent sodium channels. The main objective of research work was to the suitable enhancing solubility of carbamazepine for oral administration of capsules. The lyophilized of CBZ were prepared employing different concentrations of polaxamer 407 and skimmed milk powder in different combinations as a carriers by lyophilization solid dispersion technique using 32 factorial design. CBZ was compatible with both the polymers and it was confirmed by FTIR and DSC study. Total nine formulations were designed and are evaluated for physicochemical properties, differential scanning calorimetry, X-Ray powder diffractometry, water content, saturation solubility, compressibility and fluidity, assay, and in-vitro drug release. All of lyophilized batches showed 1.84 to 4.94 times increase in saturation solubility. Its amorphous nature was confirmed from reducing melting point with low ΔH in DSC and minimizing of RDC in XRD. Polynomial equations were developed for saturation solubility, in-vitro drug release and validity were verified by designing 2 check point formulations. The maximum drug release was observed for batch F9 (93.98±1.90%) than pure CBZ (28.38±0.10%) after 80 min. This might be due increase in wettability and decrease in crystallinity of CBZ particles with hydrophilic polymers. Formulated solid dispersions showed improvement in flow properties and compressibility of CBZ. All the batches were stable in normal temperature and humidity conditions in the form of drug contents. There were no any color changes which revealed stability of CBZ.

Keywords: Carbamazepine; amorphous solid dispersions; oral administration; lyophilization technique.