Preparation and in vitro characterization of rosuvastatin calcium incorporated methyl beta cyclodextrin and Captisol® inclusion complexes.

Despite being the most effective hypolipidemic agent, poor physicochemical properties of Rosuvastatin calcium (RCa) remain challenging obstacles in the development of pharmaceutical dosage forms. Inclusion complexes (ICs) of RCa with cyclodextrin (CD) derivatives; methyl-beta-cyclodextrin (M-ß-CD) and sulfobutylether-beta-cyclodextrin (SBE-ß-CD; Captisol®) were formulated by kneading and freeze-drying (lyophilization) methods. Pysicochemical properties of ICs were evaluated by SEM, DSC, XRD, FT-IR, 1H-NMR analyses. Entrapment efficiency (EE), water solubility, in vitro release analyses were also performed. Safety and efficacy of the ICs were analyzed by cytotoxicity and permeation studies on Caco-2 cell lines. Both CDs indicated AL type phase solubility diagrams showing that [1:1] molar ratio. Apparent stability constants (K1:1) were found to be 60.93 M-1 for M-ß-CD and 158.07 M-1 for Captisol®. High EE in the range of 93.50-105.40% was achieved. Molar solubility of RCa was increased 3.7- and 4.1-fold with M-ß-CD and Captisol® ICs, respectively. In vitro release analyses have indicated the equivalence of dissolution profiles for M-ß-CD and Captisol® based ICs to that of pure RCa (f2 > 50). Cytotoxicity studies on Caco-2 cell lines have revealed the safety of ICs for oral use. Permeability studies demonstrated that selected lyophilized F6 formulation has shown the best permeation rate with Papp value of 3.08 × 10-7 cm·s-1. Considering greater water solubility, lower toxicity, high efficiency of complexation as well as, RCa-like permeability and in vitro release behavior at pH 6.8; Captisol® based lyophilized F6 formulation was selected as the best IC to be used in oral dosage forms of RCa.

Physicochemical characterization and pharmacokinetic evaluation of rosuvastatin calcium incorporated solid lipid nanoparticles.

Rosuvastatin calcium (RCa) is a very efficient antihyperlipidemic agent, however, being a BCS class II drug, results in poor oral bioavailability. The present study focused on the enhancement of oral bioavailability of RCa with solid lipid nanoparticles (SLNs). Physicochemical properties of the particles were evaluated by particle size (PS), polidispersity index (PDI), zeta potential (ZP), DSC, FT-IR, XRD, 1H NMR analyses. Entrapment efficiency (EE), drug loading capacity (DL), in vitro release and release kinetics were also analyzed. Safety and efficacy of the formulations were analyzed by cytotoxicity, permeability and pharmacokinetic studies. PS values were ranged between ∼134 and 351 nm with homogenous size distribution (PDI ∼ 0.130-0.33) and ZP data were valued within the range of ∼-17 mV to -41 mV. The SLN2 formulation showed the best cytotoxicity test results and had medium permeability (Papp 5.72 × 10-6 cm sec-1) while pure RCa resulted in low permeability (Papp 3.08 × 10-7 cm sec-1). According to the stability analyses (3 months) 5 ±â€¯3 °C and 25 ±â€¯2 °C were found suitable storage temperatures for SLNs. Pharmacokinetic studies confirmed significant improvement in Cmax (1.4 fold) and AUClast (8.5 fold) by SLNs in comparison with the pure drug indicating the enhanced biopharmaceutical performance of the RCa loaded SLNs.

Preparation, characterization and pharmacokinetic evaluation of rosuvastatin calcium incorporated cyclodextrin-polyanhydride nanoparticles.

Objective: The aim of the study was to formulate, cyclodextrin (CD)-polyanhydride (PA) nanoparticles (CPNs) with rosuvastatin calcium (RCa) in order to enhance the poor oral bioavailability. Methods: CPNs containing RCa/CD complexes were prepared by a modified solvent displacement method and morphological analyses, particle size (PS), polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), DSC, FT-IR, XRD, 1H-NMR analyses were performed. In vitro release properties, release kinetics, cytotoxicity, in vitro permeability and pharmacokinetic studies were also studied. The stability of the formulations were evaluated during the storage period of 3 months. Results: The physicochemical studies showed that the RCa/CD complexes were well incorporated into CPNs resulted in nanosized particles (215.22 and 189.13 nm) with homogenous size distribution (PDI: 0.203 and 0.182) with relatively high incorporation capacity (76.11 and 68.18%) for the CPN1 and CPN2 formulations respectively. Sustained release of RCa from CPNs were achieved. The cytotoxicity values showed that the safety of the formulations. According to permeability studies, pure RCa had lowest permeability data (3.08 × 10-7 cm⋅s-1 Papp value) while CPNs gained higher permeability data (1.36 × 10-5 and 1.12 × 10-5 cm⋅s-1 Papp values) for the CPN1 and CPN2 formulations respectively. CPN2 formulation was selected for pharmacokinetic studies and analyses results demonstrated that approximately 8-fold relative oral bioavailability enhancement compared to the pure RCa was achieved. Conclusion: Considering the analyses results of the study, CPNs can be regarded as suitable, safe, functional oral delivery systems for RCa with enhanced oral bioavailability.