| Autor: |
Inam S; Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad 38000, Pakistan., Irfan M; Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad 38000, Pakistan., Lali NUA; Department of Medicine, Fatima Jinnah Medical University, Lahore 42000, Pakistan., Khalid Syed H; Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad 38000, Pakistan., Asghar S; Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad 38000, Pakistan., Khan IU; Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad 38000, Pakistan., Khan SU; Department of Biochemistry, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11432, Saudi Arabia., Iqbal MS; Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam bin Abdulaziz University, Alkharj 11942, Saudi Arabia., Zaheer I; Department of Pharmacology, College of Medicine, Al-Dawadmi Campus, Shaqra University, Al-Dawadmi 11961, Saudi Arabia., Khames A; Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia., Abou-Taleb HA; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Merit University (MUE), New Sohag 82755, Egypt., Abourehab MAS; Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.; Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Minia University, Minia 61519, Egypt. |
| Abstrakt: |
Poor solubility is the major challenge involved in the formulation development of new chemical entities (NCEs), as more than 40% of NCEs are practically insoluble in water. Solid dispersion (SD) is a promising technology for improving dissolution and, thereby, the bioavailability of poorly soluble drugs. This study investigates the influence of a pH-sensitive acrylate polymer, EPO, on the physicochemical properties of rosuvastatin calcium, an antihyperlipidemic drug. In silico docking was conducted with numerous polymers to predict drug polymer miscibility. The screened-out polymer was used to fabricate the binary SD of RoC in variable ratios using the co-grinding and solvent evaporation methods. The prepared formulations were assessed for physiochemical parameters such as saturation solubility, drug content and in vitro drug release. The optimized formulations were further ruled out using solid-state characterization (FTIR, DSC, XRD and SEM) and in vitro cytotoxicity. The results revealed that all SDs profoundly increased solubility as well as drug release. However, the formulation RSE-2, with a remarkable 71.88-fold increase in solubility, presented 92% of drug release in the initial 5 min. The molecular interaction studied using FTIR, XRD, DSC and SEM analysis evidenced the improvement of in vitro dissolution. The enhancement in solubility of RoC may be important for the modulation of the dyslipidemia response. Therefore, pharmacodynamic activity was conducted for optimized formulations. Our findings suggested an ameliorative effect of RSE-2 in dyslipidemia and its associated complications. Moreover, RSE-2 exhibited nonexistence of cytotoxicity against human liver cell lines. Convincingly, this study demonstrates that SD of RoC can be successfully fabricated by EPO, and have all the characteristics that are favourable for superior dissolution and better therapeutic response to the drug. |
