Evaluation of various processes for simultaneous complexation and granulation to incorporate drug–cyclodextrin complexes into solid dosage forms

Abstract

Insoluble drugs often formulated with various excipients to enhance the dissolution. Cyclodextrins (CDs) are widely used excipients to improve dissolution profile of poorly soluble drugs. Drug-CD complexation process is complex and often requires multiple processes to produce solid dosage form. Hence, this study explored commonly used granulation processes for simultaneous complexation and granulation. Poorly soluble drugs ibuprofen and glyburide were selected as experimental drugs. Co-evaporation of drug:CD mixture from a solvent followed by wet granulation with water was considered as standard process for comparison. Spray granulation and fluid bed processing (FBP) using drug:CD solution in ethanol were evaluated as an alternative processes. The dissolution data of glyburide tablets indicated that tablets produced by spray granulation, FBP and co-evaporation-granulation have almost identical dissolution profile in water and 0.1% SLS (>70% in water and >60% in SLS versus 30 and 34%, respectively for plain tablet, in 120 min). Similarly, ibuprofen:CD tablets produced by co-evaporation-granulation and FBP displayed similar dissolution profile in 0.01 M HCl (pH 2.0) and buffer pH 5.5 (>90 and 100% versus 44 and 80% respectively for plain tablets, 120 min). Results of this study demonstrated that spray granulation is simple and cost effective process for low dose poorly soluble drugs to incorporate drug:CD complex into solid dosage form, whereas FBP is suitable for poorly soluble drugs with moderate dose.

Development of carvedilol-cyclodextrin inclusion complexes using fluid-bed granulation: a novel solid-state complexation alternative with technological advantages

“…The authors showed a significant improvement in drug dissolution from pellets based on complexes of the drug with cyclodextrins. However, there have been few reports in the literature of the complexation of drugs with cyclodextrins using FB granulation . In this study, we explored FB granulation as a possible method of producing inclusion complexes and compared it with SD, one of the most efficient methods of obtaining inclusion complex in the solid state.…”

“…Some studies have reported the drying of drug : cyclodextrin solutions by spouted or FB apparatus . In addition, there are reports on the preparation of solid complexes by FB coating and, more recently, FB granulation …”

“…[23,24] In addition, there are reports on the preparation of solid complexes by FB coating [25,26] and, more recently, FB granulation. [27] Accordingly, improvements in the inclusion complex formation methods of CARV : cyclodextrin, making them more suitable for industrial processing, may finally provide a commercial product of CARV : cyclodextrin in the form of inclusion complexes. This study sought to evaluate carvedilol inclusion complexes with cyclodextrins formed using FB granulation.…”