Effect of Different Stabilizers and Polymers on Spherical Agglomerates of Gresiofulvine by Emulsion Solvent

ABSTARCT:Emulsion Solovent Diffusion (EDS) technique combines crystallization and agglomeration directly to generate spherical agglomerates with improved micromeretic properties, thus obviating need for further processing by granulation and agglomeration. The present study was focused on spherical crystallization of an antifungal drug Gresiofulvine (GRV) using above mentioned ESD technique in which distilled water as an external phase and the internal phase consisted of dichloromethane which acts as good solvent as well as bridging liquid for recrystallization and agglomeration process. Apart from being poorly water-soluble, GRV exhibits poor flow and compressibility owing to its irregular shaped crystal habit and electrostatic charge. The spherical agglomeration was carried out in the presence of different polymers (hydroxyl propyl cellulose (HPC), Eudragit-RLPO) and stabilizers (Beta cyclodextrin, poloxomer-F68 and Polyethylene glycol. The pure GRV and the prepared agglomerates were characterized in terms of production yield, drug content, solubility, in-vitro release profile, flowability,density,packability , thermal behavior (differential scanning calorimetry-DSC), X-ray diffraction (XRD), Fourier transforms infra red spectroscopy (FTIR).The optimized spherical agglomerates exhibited excellent physicochemical and micromeritic properties, solubility, dissolution rate, flowability and packability when compared with pure drug as well as the physical mixture of drug with excipients.The XRD also revealed a characteristic decrease in crystallinity. The dissolution studies demonstrated a marked increase in the dissolution rate in comparison with pure drug and physical mixture. The DSC showed a decrease in the melting enthalpy indicating disorder in the crystalline content. FTIR study reveals there are no chemical changes in prepared recrystallized agglomerates. The considerable improvement in the dissolution rate of GRV from optimized crystal formulation was attributed to the wetting effect of polymers, decreased drug crystallinity, altered surface morphology and micronization.If this process can be scaled-up to manufacturing level, this technology has the potential to provide the directly compressed spherical agglomerates with improving the physicochemical and micromeritic properties.