Understanding the Effects of Associated Factors in the Development of Microsponge-Based Drug Delivery: a Statistical Quality by Design (QbD) Approach Towards Optimization.

The investigation aims to prepare, identify, analyse, and understand the effects of different variables and constant factors associated with developing drug-loaded microsponge formulation by altering variables using the experiment's design. A series of drug formulations were prepared by alteration of variables using the design of experiment (DoE). Shape factors were kept constant. Response surface methodology (RSM) was utilized to optimize the preparation and analyse factors and variables. The RSM and QbD make the process easy to scale up and reproducible to minimize batch-to-batch variation. Critical process attributes (CPAs), such as particle size, yield, and drug entrapment, were analysed and comprehended in the development process to estimate the risk of microsponge-based formulation and method stability. Critical process parameters (CPPs) were identified by trial and error. QbD-driven quasi-emulsion solvent evaporation method was adopted to emulsify the dispersed phase within a continuous aqueous phase to develop the microsponges. The investigation confirmed that the effects of changes in controlling factors were most prominent on response variables. Each response was found in a broad range in terms of average particle diameter (337-461 µm), entrapment efficiency (77.69-94.38%) of the drug, and product yield (76.91-96.38%). The optimum results are a yield of ~ 96%, an average particle size of 347 µm, and entrapment efficiency of ~ 93.55%. An analysis of ANOVA (P value < 0.05) and models were validated. A constant rate of drug release from the optimized product was observed for a period (8 h) with a drug release of 75%. The developed method is reproducible, stable, and reliable.