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

Abstract

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 × 10⁻⁷cm⋅s⁻¹ P_app value) while CPNs gained higher permeability data (1.36 × 10⁻⁵ and 1.12 × 10⁻⁵cm⋅s⁻¹ P_app 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.

Keywords:

• Rosuvastatin calcium
• inclusion complexes
• cyclodextrins
• polyanhydride nanoparticles
• bioavailability

Acknowledgement

Authors would like acknowledge Anadolu University, Faculty of Pharmacy, Doping and Narcotics Analysis Laboratory (DOPNA-LAB) for FT-IR and ¹H-NMR Analyses; Eskişehir Technical University, Faculty of Science, department of Chemistry for SEM analyses and Eskişehir Technical University, Faculty of Engineering, Ceramic Research Center for XRD analyses.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by Anadolu University Scientific Research Project Foundation [No. 1404S289].