Hard gelatin capsules containing hot melt extruded solid crystal suspension of carbamazepine for improving dissolution: Preparation and in vitro evaluation

Aqueous solubility is one of the key parameters for achieving the desired drug concentration in systemic cir-culation for better therapeutic outcomes. Carbamazepine (CBZ) is practically insoluble in water, is a BCS class II drug, and exhibits dissolution-dependent oral bioavailability. This study explored a novel application of hot-melt extrusion in the manufacture and development of a thermodynamically stable solid crystal suspension (SCS) to improve the solubility and dissolution rate of CBZ. The SCSs were prepared using sugar alcohols, such as mannitol or xylitol, as crystalline carriers. The drug-sugar blend was processed by hot melt extrusion up to 40% (w/w) drug loading. The extruded SCS was evaluated for drug content, saturation solubility, differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), in vitro release, and stability studies. The physicochemical characterization revealed the highly crystalline existence of pure drug, pure carriers, and extruded SCS. FTIR analysis did not reveal any physical or chemical incompatibilities between the drug and sugar alcohols and showed a homogeneous CBZ distribution within respective crystalline carriers. The SEM micrographs of the solidified SCS revealed the presence of approximately 100 mu m crystalline agglomerates. In vitro dissolution and solubility studies showed that the CBZ dissolution rate and solubility were improved significantly from both crystalline carriers for all tested drug loads. The SCSs showed no significant changes in drug content, in vitro release profiles, and thermal characteristics over 3 months of storage at accelerated stability conditions (40 +/- 2 degrees C/75 +/- 5% RH). As a result, it can be inferred that the SCS strategy can be employed as a contemporary alternative technique to improve the dissolution rate of BCS class II drugs via HME technology.

Automated summary

This study explored the use of hot-melt extrusion to develop a thermodynamically stable solid crystal suspension (SCS) for improving the solubility and dissolution rate of carbamazepine (CBZ), a BCS class II drug. The SCSs, prepared using sugar alcohols as crystalline carriers, showed significantly improved dissolution rate and solubility. Stability studies confirmed that the SCSs maintained drug content, in vitro release profiles, and thermal characteristics over 3 months.