Design and Development of a Microwave Generated Lactose Monohydrate - Microcrystalline Cellulose Based Multifunctional Excipient Composites for Tablet Formulation using Box–Behnken Design

摘要

The concept of co-processing as a particle engineering technique continues to be used as a tool to enhance the functionality of several existing excipients. This important research was designed to improve the functionality of lactose monohydrate as excipient for direct compression by co-processing with microcrystalline cellulose. Microwave induced diffusion technique was first utilized for manufacturing Co processed lactose monohydrate (LM) - microcrystalline cellulose (MC) composites. The objective of the research was to obtain synergistic effects, incorporating better tablet adherence and hardness capacity. Box-Behnken experimental design was worked out to optimize the proportion of the primary excipients for the co-processed excipient. Fifteen experiments were carried out to assess the effect of primary excipients and mixing time required to prepare a slurry for microwaving treatment on percent fines, angle of repose, Carr’s index, friability, tensile strength, disintegration time as responses. The combination of the co-processed excipient that constructed significant characteristics after optimization was observed to be 70 % alpha-Lactose-monohydrate and 30 % microcrystalline cellulose. Consequently, Microcrystalline Cellulose-Lactose composites (MCLM), a co-processed excipient, was developed that offers functionality for direct compression, as a result of given flowability and compactability. Solid-state characterization was performed on optimized composites to ascertain its particle size, shape, distribution, surface morphology, degree of crystallinity, hygroscopicity, compatibility etc. employing proven analytical methods. Powder characteristics were determined by bulk and tapped densities, angle of repose, porosity, lubricant sensitivity ratio, dilution potential etc. The compaction patterns of MCLM were assessed employing Heckel and Kawakita equations and the compressibility, tabletability, compactability (CTC) profile was determined compared to the physical mixture of the native excipients and Cellactose. Tablets were developed by direct compression using paracetamol as the drug of choice. The results imply that microwave generated MCLM composites offers improved properties in comparison with native MC and LM. The current study highlights the concept of microwave drying technique as a cost-effective means for manufacturing multifunctional directly compressible excipient in comparison to the spray-drying technique.