Evaluating the discriminatory power of a dissolution assay for rosuvastatin calcium capsules: Solid-state properties and dissolution media

Marilene Lopes Ângelo,Marcus Vinicus De Faria Ramos,André Luís Morais Ruela,Cristina Martiniano Montanari,Magali Benjamim De Araújo,Anna Clara Marques Ferreira,Lucélia Magalhães Da Silva

doi:10.1590/s2175-97902019000117520

Abstract

We propose to evaluate the dissolution properties of rosuvastatin calcium (ROSC) capsules in different media to characterize the discriminatory power of the assay method. Dissolution assays were performed in media with different pH, and including the surfactant sodium dodecyl sulfate (SDS). Several immediaterelease formulations were manufactured using the commercial raw material characterized as amorphous solid. The hydrophobic adjutant magnesium stearate was employed in some formulations due to its negative effect in the wettability and dissolution efficacy of solid dosages. These formulations showed the lower dissolution efficacy values in media without surfactant; however, when SDS was added to the medium, the dissolution efficacy increased, and the discriminatory power was lost. In spite of micellar solubilization does not increase the ROSC solubility, it modifies the discriminatory power of the assay method, increasing the wettability of the powder mixtures. The crystalline form M of ROSC was recrystallized in our laboratory, and it showed lower solubility in water than amorphous solid. However, its dissolution properties were not influenced by SDS. These results are important to develop dissolution assays for other hydrophilic drugs with increased water solubility, once that dissolution media with surfactants increase the wettability of the formulations, leading to an overrated dissolution rate.

Highlights

Rosuvastatin calcium (ROSC) (Figure 1) is a lipidlowering drug that competitively inhibits the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase in the liver
We evaluated the discriminatory power of a dissolution assay for ROSC capsules
Besides the ROSC has a similar solubility in acetate buffer pH 4.5 with or without sodium dodecyl sulfate (SDS), the results demonstrated that the presence of SDS increased the DE% of formulation B; the surfactant increased the wettability of this formulation

Summary

Introduction

Rosuvastatin calcium (ROSC) (Figure 1) is a lipidlowering drug that competitively inhibits the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase in the liver. The equilibrium solubility of ROSC (amorphous solid-state and crystalline form M) was evaluated by the shake-flask method in different aqueous media. The selectivity of the dissolution assay method was determined by evaluating the solutions of the placebo, standard solutions of ROSC at concentration of 20 μg mL−1, and sample solutions of the powder mixture of the capsules diluted at this same concentration.

Results

Conclusion