Saba Irshad1, Ikram Ullah Khan2, Syed Haroon Khalid1, Sajid Asghar1, Muhammad Irfan1, Ikrima Khalid1, Nadeem Sabir3, Adnan Ali3, Ahmad Nawaz Khan4, Abid Mehmood Yousaf5, Talib Hussain5, Yasser Shahzad6. 1. Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan. 2. Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan. ikramglt@gmail.com. 3. Department of Physics, Government College University Faisalabad, Faisalabad, Pakistan. 4. Department of Materials Engineering, School of Chemical and Materials Engineering (SCME), National University of Sciences and Technology (NUST), Islamabad, Pakistan. 5. Drug Delivery Research Group, Department of Pharmacy, COMSATS University Islamabad (CUI), Lahore Campus, Lahore, Pakistan. 6. Drug Delivery Research Group, Department of Pharmacy, COMSATS University Islamabad (CUI), Lahore Campus, Lahore, Pakistan. y.shahzad@live.com.
Abstract
BACKGROUND: Clopidogrel (CLOP) is an antiplatelet drug with poor solubility in intestinal fluid, which limits its bioavailability after oral administration. OBJECTIVES: Current study focuses on developing site-specific floating microcarriers of CLOP using solvent diffusion evaporation method (SDEM) for retaining the drug in the stomach, thus improving the solubility of drug for better absorption. METHODS: SDEM was employed to formulate floating microcarriers using lipidic excipients, namely Gelucires (GL) to impart floating properties, in combination with ethyl cellulose as release retarding polymer. RESULTS: Prepared particles were 169 ± 6 μm to 375 ± 13 μm in size, whilst encapsulation efficiency was ranged from 39.6 ± 0.60% to 96.50 ± 3.50%. Electron micrographs depicted discrete spherical microcarriers with porous structure, which amplified with increasing HLB value of GL and concentration of Eudragit E100. FTIR study confirmed absence of major drug polymer interactions while DSC and XRD studies revealed the presence of non-crystalline nature of drug in all formulations. Drug release at pH 1.2 enhanced more than 2-folds with increasing HLB value with 32% cumulative drug release for GL 43/01 and 69% for GL 50/13. More interestingly, adding various proportions of Eudragit E100 to GL 43/01 based formulations resulted in increased drug release as high as 71%. In all formulations, the drug release followed diffusion dependent process. CONCLUSION: It is envisaged that this formulation strategy for CLOP is promising and could possibly be tested in future for its in vivo performance. Graphical abstract Lipid based floating microcarriers of clopidogrel.
BACKGROUND:Clopidogrel (CLOP) is an antiplatelet drug with poor solubility in intestinal fluid, which limits its bioavailability after oral administration. OBJECTIVES: Current study focuses on developing site-specific floating microcarriers of CLOP using solvent diffusion evaporation method (SDEM) for retaining the drug in the stomach, thus improving the solubility of drug for better absorption. METHODS:SDEM was employed to formulate floating microcarriers using lipidic excipients, namely Gelucires (GL) to impart floating properties, in combination with ethyl cellulose as release retarding polymer. RESULTS: Prepared particles were 169 ± 6 μm to 375 ± 13 μm in size, whilst encapsulation efficiency was ranged from 39.6 ± 0.60% to 96.50 ± 3.50%. Electron micrographs depicted discrete spherical microcarriers with porous structure, which amplified with increasing HLB value of GL and concentration of Eudragit E100. FTIR study confirmed absence of major drug polymer interactions while DSC and XRD studies revealed the presence of non-crystalline nature of drug in all formulations. Drug release at pH 1.2 enhanced more than 2-folds with increasing HLB value with 32% cumulative drug release for GL 43/01 and 69% for GL 50/13. More interestingly, adding various proportions of Eudragit E100 to GL 43/01 based formulations resulted in increased drug release as high as 71%. In all formulations, the drug release followed diffusion dependent process. CONCLUSION: It is envisaged that this formulation strategy for CLOP is promising and could possibly be tested in future for its in vivo performance. Graphical abstract Lipid based floating microcarriers of clopidogrel.
Authors: Laura Bond; Stephanie Allen; Martyn C Davies; Clive J Roberts; Arif P Shivji; Saul J B Tendler; Phillip M Williams; Jianxin Zhang Journal: Int J Pharm Date: 2002-08-28 Impact factor: 5.875
Authors: Jelena Mudrić; Katarina Šavikin; Ljiljana Đekić; Stefan Pavlović; Ivana Kurćubić; Svetlana Ibrić; Jelena Đuriš Journal: Pharmaceutics Date: 2021-12-06 Impact factor: 6.321