| Autor: |
Zidan MF; a Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Al-Azhar University , Cairo , Egypt., Ibrahim HM; a Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Al-Azhar University , Cairo , Egypt., Afouna MI; a Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Al-Azhar University , Cairo , Egypt., Ibrahim EA; a Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Al-Azhar University , Cairo , Egypt. |
| Jazyk: |
angličtina |
| Zdroj: |
Drug development and industrial pharmacy [Drug Dev Ind Pharm] 2018 Aug; Vol. 44 (8), pp. 1243-1253. Date of Electronic Publication: 2018 Feb 26. |
| DOI: |
10.1080/03639045.2018.1442844 |
| Abstrakt: |
The aim of this study was to explore the feasibility of complexing the poorly water-soluble drug atorvastatin calcium (AC) with β-cyclodextrin (β-CD) based nanosponges (NS), which offer advantages of improving dissolution rate and eventually oral bioavailability. Blank NS were fabricated at first by reacting β-CD with the cross-linker carbonyldiimidazole at different molar ratios (1:2, 1:4, and 1:8), then NS of highest solubilization extent for AC were complexed with AC. AC loaded NS (AC-NS) were characterized for various physicochemical properties. Pharmacokinetic, pharmacodynamics and histological finding of AC-NS were performed in rats. The prepared AC-NS showed particles size ranged from 408.7 ± 12.9 to 423 ± 15.9 nm while zeta potential values varied from -21.7 ± 0.90 to -22.7 ± 0.85 mV. The loading capacity varied from 17.9 ± 1.21 to 34.1 ± 1.16%. DSC, FT-IR, and PXRD studies confirmed the complexation of AC with NS and amorphous state of the drug in the complex. AC-NS displayed a biphasic release pattern with increase in the dissolution rate of AC as compared to plain AC. Oral administration of AC-NS (1:4 w/w, drug: NS) to rats led to 2.13-folds increase in the bioavailability as compared to AC suspension. Pharmacodynamics studies in rats with fatty liver revealed significant reduction (p < .05) in total cholesterol, triglyceride, LDL-C and increased level of beneficial HDL-C along with improvement in the associated liver steatosis as confirmed through photomicrographs of liver sections. In this study, we confirmed that complexation of AC with NS would be a viable approach for improving oral bioavailability and in vivo performance of AC. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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