Fawaz N S Al-Heibshy1, Ebru Başaran2, Rana Arslan3, Naile Öztürk4, İmran Vural4, Müzeyyen Demirel2. 1. Doctorate Program in Pharmaceutical Technology, Graduate School of Health Sciences, Anadolu University , Eskişehir , Turkey. 2. Faculty of Pharmacy, Department of Pharmaceutical Technology, Anadolu University , Eskişehir , Turkey. 3. Faculty of Pharmacy, Department of Pharmacology, Anadolu University , Eskişehir , Turkey. 4. Faculty of Pharmacy, Department of Pharmaceutical Technology, Hacettepe University , Ankara , Turkey.
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 × 10-7 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.
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.
Authors: Sana Inam; Muhammad Irfan; Noor Ul Ain Lali; Haroon Khalid Syed; Sajid Asghar; Ikram Ullah Khan; Salah-Ud-Din Khan; Muhammad Shahid Iqbal; Imran Zaheer; Ahmed Khames; Heba A Abou-Taleb; Mohammad A S Abourehab Journal: Pharmaceuticals (Basel) Date: 2022-04-18