Study On Influence Of Process Parameters On Quality Of Lovastatin Microspheres By Design Of Experiments

Scale-up of microspheres is major challenge at large scale manufacturing. The foremost objective of this research was to study the impact of key process parameters and formulation parameters, which are significant during scale-up, on the quality characteristic of the lovastatin microspheres. Emulsion solvent evaporation technique was explored to generate microspheres. Including the amount & type of polymer, process parameters like viscosity of the internal and temperatures used for evaporation of the solvent were taken as the factors. The key quality control parameters of the microspheres viz. entrapment efficiency and drug release rate constant were considered as the response variables on which the influence of the factors to be studied. Under response surface methodology, historical data design was employed to design of experiments (DoE) analysis using Stat Ease Design Expert software. Apart from the responses, the microspheres prepared were studied for flow properties, percentage yield and surface morphology. Scanning electron microscopy (SEM) images illustrated that the microspheres were
almost spherical having different surface texture for different polymers. Entrapment efficiency results were found to be in the range of 78.43 – 93.83%; and the values of drug release rate constant were to be in the range of 0.09 – 1.2 h-1 for all the prepared microspheres. Response surface linear model was selected to elucidate the relation between the factors and the responses. Analysis of variance (ANOVA) of the selected model indicated that all the selected factors including the key process parameters had significant influence on both the responses. Later, graphical optimization was performed with the set desirability of maximizing the entrapment efficiency and minimizing the drug release rate constant. The microspheres obtained from the optimised formula were found to have 92.4% entrapment efficiency and 0.102 h-1 as the drug release rate constant. These results signified that the selected factors including the process parameters had substantial influence on the quality characteristics of the prepared microspheres.