Carbamazepine and Polyethylene Glycol Solid Dispersions: Preparation, in Vitro Dissolution, and Characterization

Abstract

The objective of this study was to prepare solid dispersions of carbamazepine (CBZ) using polyethylene glycol (PEG) 4000 and PEG 6000, measure the dissolution, and characterize using x-ray diffraction, DSC, and IR spectroscopy. Solid dispersions were prepared by either the melt or solvent methods. A comparison of dissolution profiles of the solid dispersions indicated dramatic increases in the rate and extent of CBZ dissolution from solid dispersions. The dissolution of physical mixtures provided evidence of the solubilizing effects of PEGs. Untreated CBZ exhibited 10.09 ± 2.92% dissolution in 10 min (D_l0); whereas, a melt of PEG 6000 and CBZ at a ratio of 6: 1 provided 36.49 ± 1.97% and a melt of PEG 4000 and CBZ at a ratio of 6: 1 gave a D₁₀ of 23.59 ± 1.45%. The rate and extent of dissolution of CBZ were significantly higher when blends of the PEGs were employed to prepare solid dispersion. The melt method provided significantly higher rate and extent of dissolution of CBZ than the solvent method. Also, the rate and extent of dissolution of CBZ were significantly greater when the solid dispersion was cooled at room temperature as opposed to with ice (faster). X-ray diffractometry revealed almost a complete loss of crystallinity of CBZ in solid dispersions. IR spectrometry indicated an increase in amorphocity of the PEGs after melting. IR spectra suggested that no complexation occurred between the PEGs and CBZ. Alterations in the crystallinity of the system were also supported by the DSC thermograms. Decreasing heats of fusion implied decrease in crystallinity, which would be expected to provide greater dissolution rates. Peak melting temperatures obtained from the thermograms ruled out the possibility of the formation of a eutectic mixture. However, the formation of solid solution could also be a possible mechanism for the increase in dissolution.