Simvastatin is classified as a Biopharmaceutics Classification System Class – II active pharmaceutical ingredient, which means that it has low water solubility and high permeability. The poor water solubility of simvastatin leads to concerns with chronic use, due to it's lower bioavailability. The use of lipid-based drug delivery systems has emerged as one of the approaches to increase the solubility and consequently bioavailability of poorly water soluble lipophilic active pharmaceutical ingredients. In addition, lipid-based systems may, under appropriate conditions, also reduce the effect of first-pass metabolism by exploiting an alternative route of absorption through the lymphatic circulation.
Liquid emulsions offer many advantages of lipid-based systems, but they also have some disadvantages, such as physical instability and reduced chemical stability of active pharmaceutical ingredient. By converting emulsions into dry emulsions, we tried to design a solid dosage form for oral application, which would eliminate the disadvantages of liquid emulsions and maintain the advantages of lipid-based systems by redispersion. Through the spray drying technology we formed particles that allowed us to automatically redisperse the dry emulsion in an aqueous medium. Dry emulsions produced were evaluated in terms of particle size distribution, process yield, flow properties, moisture content, stability of simvastatin in dry emulsion, emulsion reconstitution ability, efficiency of incorporation of the active ingredient and dissolution profile. The results of preliminary formulation development in the initial stages of experimental work served as a starting point for determining the boundaries of the independent variables and setting the experimental design. The independent variables included: concentration of non-aqueous components, oil and emulsifier mass fraction, nozzle geometry and nozzle pressure. Based on the results of the experimental design experiments, we set up models with relatively high determination coefficients and optimize both the emulsion composition and the process parameters in terms of key product quality attributes. We optimized the adequacy of redispersion, chemical stability of simvastatin, and the effectiveness of simvastatin incorporation. Optimization adequacy has been demonstrated in improving the one-month stability of simvastatin in dry emulsions and in the improved reconstitution of the emulsion. By preparing an optimized formulation and measuring the response, we have not confirmed the drug loading model, so we cannot state which parameters and to what extent affect the drug loading of simvastatin into dry emulsions. Enhanced dissolution profile, compared to currently available products on the market, indicates the potential for increased bioavailability after oral administration.
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