Process optimization and characterization of carvedilol solid dispersion with hydroxypropyl-beta-cyclodextrin and tartaric acid

作者：Yuvaraja K^*; Das Sanjoy Kumar; Khanam Jasmina

来源：Korean Journal of Chemical Engineering, 2015, 32(1): 132-140.

DOI：10.1007/s11814-014-0192-2

• Simplex Lattice Design
• Ionized Carvedilol-hydroxypropyl-beta-cyclodextrin-tartaric Acid Complex
• Dissolution Rate
• Solubility

The present investigation concerns the experimental design in preparing a solid dispersion of ionized carvedilol with hydroxypropyl-beta-cyclodextrin (HP beta CD), tartaric acid (TA) by adopting 'kneading technique'. Simplex lattice design has been chosen to develop model equations that correlate the process variables such as HP beta CD (mg), TA (mg), and kneading time (min) with the response variables, such as solubility (mg/mL) and drug release (%) from the solid dispersion. Software-generated ANOVA results confirmed the sufficiency of model equations. Results predicted by model equations are in good agreement with that of experimental results. Optimized formulation with variables 'CV: HP beta CD: TA-kneading time' (200mg: 689.6mg: 227.6mg-45 min) showed complete drug release (similar to 99%) within 15 min and enhanced solubility of 1.89mg/mL. The instrumental analysis (DSC, XRD& FTIR) of the optimized solid dispersion suggests a transformation of crystallinity of drug to amorphous form, due to its complexation with HP beta CD. Hence, this combination of drug and carriers suggests an improvement of carvedilol bioavailability.

• 出版日期2015-1