The Study of the Influence of Formulation and Process Variables on the Functional Attributes of Simvastatin–Phospholipid Complex
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The aim of the present study was to examine the influence of the formulation and process variables on the entrapment efficiency of simvastatin–phospholipid complex (SPC), prepared with a goal of improving the solubility and permeability of simvastatin.
The SPC was prepared using a solvent evaporation method. The influence of formulation and process variables on simvastatin entrapment was assessed using a central composite design. An additional SPC was prepared using the optimized variables from the developed quadratic model. This formulation was characterized for its physical–chemical properties. The functional attributes of the optimized SPC formulation were analyzed by apparent aqueous solubility analysis, in vitro dissolution studies, dissolution efficiency analysis, and ex vivo permeability studies.
The factors studied were found to significantly influence the entrapment efficiency. The developed model was validated using the optimized levels of formulation and process variables. The physical–chemical characterization confirmed a formation of the complex. The optimized SPC demonstrated over 25-fold higher aqueous solubility of simvastatin, compared to that of pure simvastatin. The optimized SPC exhibited a significantly higher rate and extent of simvastatin dissolution (>98 %), compared to that of pure simvastatin (∼16 %). The calculated dissolution efficiency was also found to be significantly higher for the SPC (∼54 %), compared to that of pure simvastatin (∼8 %). Finally, the optimized SPC exhibited a significantly higher simvastatin permeability (>78 %), compared to that of pure simvastatin (∼11 %).
The present study shows that SPC can be a promising strategy for improving the delivery of simvastatin and similar drugs with low aqueous solubility.
KeywordsBCS class II Solubility Dissolution QbD Design of Experiment (DOE) Phospholipids
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