Preparation and optimization of multi-functional directly compressible excipient: an integrated approach of principal component analysis and design of experiments.

Developing a new excipient and obtaining its market approval is an expensive, time-consuming, and complex process. The application of a multivariate analytical approach - principal component analysis (PCA) - in combination with the design of experiments (DoE) approach can make the process of developing co-processed excipient cost-effective and rapid. The present investigation was aimed to demonstrate the applicability of the DoE approach and PCA in developing a co-processed excipient by using the spray drying technique. The preliminary studies suggested a significant effect of inlet air temperature (X 1) and polymer ratio [chitosan chlorhydrate (CC): mannitol - X 2) on critical product characteristics so they were selected as independent variables in 32 full factorial design. The result of regression analysis suggested a significant effect of both independent variables on all response variables. The PCA of practically obtained value suggested a strong effect of all the selected response variables on the model. The prepared co-processed excipient had better tableting properties compared to the physical mixture of excipients and was able to accommodate more than 80% drug without compromising the flow property and compressibility. The present investigation successfully proved the applicability PCA and DoE approach as an effective and rapid tool for optimizing process parameters and formulation composition for preparing a directly compressible co-processed excipient.

Co-processing of cefuroxime axetil by spray drying technique for improving compressibility and flow property.

The aim of the present investigation was to improve the compressibility and flow property of cefuroxime axetil by co-processing it with mannitol and chitosan chlorhydrate using spray drying method. 32 full factorial design, having inlet air temperature and mannitol: chitosan chlorhydrate ratio as independent variables was used for the optimization. Statistical analysis of obtained results revealed that both independent variables had significant effect on response variables (p value < .05). Evaluation of dependent variables suggested, excellent to good flow properties (angle of repose, Carr's index, and Hausner's ratio) for all prepared batches. Desirability function was used for the selection of the optimized batch which was evaluated for Kawakita's equation, Heckel's plot to assess compression behavior of co-processed product under applied pressure. Result of this analysis revealed that the optimized batch product had better compressibility than physical mixture. The tablets prepared by directly compressing spray-dried product, exhibited excellent tensile strength acceptable friability (<1%) and similar release profile when compared with marketed formulation (Similarity factor 89.24 and dissimilarity factor 1.79). So the results of the present investigation concluded that cefuroxime axetil was successfully co-processed with above mentioned excipients by using spray drying method to make it directly compressible.