Preparation of atorvastatin and ezetimibe solid dispersions and nanoparticles and evaluation of their dissolution rate and physicochemical properties

Abstract

Introduction: Low aqueous solubility remains a major concern in the development of pharmaceutical formulations. Solid dispersions are considered as one of the most useful and practical approaches in delivery of poorly water soluble drugs. Objectives: In the present study, solvent evaporation technique and electrospraying method were applied for the preparation of solid dispersions (SDs) and nano-solid dispersions (N-SDs) of atorvastatin calcium (ATV), ezetimibe (EZT) and ATV/EZT combination as poorly water-soluble drugs. Methods: All SD and N-SD formulations were prepared using polyvinylpyrrolidone K30 as an amorphous carrier in different drug to polymer ratios. The prepared formulations were further investigated for their morphological, physicochemical and dissolution properties. Due to the closely overlapping spectral bands of the mentioned drugs, partial least square method was applied in order to evaluate ATV and EZT dissolution profiles in their combined mixtures. Moreover, in vivo efficiency of the prepared SDs was also examined through measurement of serum lipid levels, liver index and histological analysis of the liver tissue in hyperlipidemic rats. Results: Differential scanning calorimetry and powder X-ray diffractometery studies showed that the crystallinity of the drugs were notably decreased during the preparation process. Fourier transformed infrared spectroscopic studies revealed hydrogen-bonding interaction between the drug and polymer in SDs together with N-SDs, which could be result in the improved physical stability. All prepared formulations showed enhanced release for both drugs. Dissolution behavior of N-SDs in 1: 1 drug to polymer ratio was comparable to that of corresponding SDs in 1: 5 drug: polymer ratio, which was indicative of the improved performance of N-SDs. In vivo studies revealed that oral administration of ATV and EZT, individually and in combination form, led to a significant decline (P< 0.05) in serum level of total cholesterol and low density lipoprotein-cholesterol. Moreover, treatment with SD formulations exhibited more beneficial effects on the liver steatosis. Conclusion: According to the obtained results, the in vivo efficiency of the formulations could be affected by their dissolution properties. In the present study, considering the superior performance of N-SDs, it was concluded that the electrospraying method could be taken into account as a novel and effective method in delivery of poorly water-soluble drugs.