Abstract
Abstract
 The purpose of our study was to develop Dabigatran Etexilate loaded nanostructured lipid carriers (DE-NLCs) using Glyceryl monostearate and Oleic acid as lipid matrix, and to estimate the potential of the developed delivery system to improve oral absorption of low bioavailability drug, different Oleic acid ratios effect on particle size, zeta potential, entrapment efficiency and loading capacity were studied, the optimized DE-NLCs shows a particle size within the nanorange, the zeta potential (ZP) was 33.81±0.73mV with drug entrapment efficiency (EE%) of 92.42±2.31% and a loading capacity (DL%) of 7.69±0.17%. about 92% of drug was released in 24hr in a controlled manner, the ex-vivo intestinal permeation study using the non-everted sac model shows four folds increment in the permeation of DE-NLCs compared to dabigatran etexilate suspension (DE-S).
Highlights
Chronic anti-coagulation therapy is essential for the prophylaxis and treatment of acute venous thromboembolism (VTE) and including the prevention of cardiogenic thromboembolism in patients with atrial fibrillation and myocardial infarction, VTE is common in traumatic patient or those undergoing major surgical operations or with underlying malignancy and in patients with prolonged immobilization, VTE is an emergency complication with an elevated morbidity and mortality rate, prophylaxis of thrombotic events is considered as standard of care )1,2(
The improvement in oral bioavailability that gained by using Nanostructured lipid carriers (NLCs) as a drug delivery vehicle was related to the fact that NLCs are absorbed mainly through the lymphatic system avoiding the first pas effect, NLCs mechanism of transportation involve the participation of clathrin and caveolae in their transcytosis and it has a permeability glycoprotein (P-gp) efflux pump modulation activity and eventually, enhancing the overall permeability of the encapsulated drug [6, 7, 8]
The lipid matrix of NLCs will be converted by the intestinal lipase to mono, di and triglycerides together with fatty acids that interact with the intestinal bile salts to form a mixed micelle system which has a greater solubilizing capacity of the poorly water soluble drug that delivering it across the stagnant unstirred water layer to the enterocyte and increasing their intestinal permeability [9, 10]
Summary
Chronic anti-coagulation therapy is essential for the prophylaxis and treatment of acute venous thromboembolism (VTE) and including the prevention of cardiogenic thromboembolism in patients with atrial fibrillation and myocardial infarction, VTE is common in traumatic patient or those undergoing major surgical operations or with underlying malignancy and in patients with prolonged immobilization, VTE is an emergency complication with an elevated morbidity and mortality rate, prophylaxis of thrombotic events is considered as standard of care )1,2(. DE shows very low oral bioavailability (3 -7 %) and this is related to the pH dependent aqueous solubility of the drug and permeability glycoprotein (P-gp) mediated efflux [3, 4]. Ex-vivo permeation study of dabigatran etexilate loaded NLCs. a novel drug delivery system should be designed to improve its oral bioavailability by overcoming these limitations. The improvement in oral bioavailability that gained by using NLCs as a drug delivery vehicle was related to the fact that NLCs are absorbed mainly through the lymphatic system avoiding the first pas effect, NLCs mechanism of transportation involve the participation of clathrin and caveolae in their transcytosis and it has a P-gp efflux pump modulation activity and eventually, enhancing the overall permeability of the encapsulated drug [6, 7, 8]. The aim of the present work was to evaluate the NLCs as a mean to improve the intestinal permeability and the oral bioavailability of DE development of DE-NLCs using a rational mixture of solid and liquid lipids together with surfactant stabilizer, and the prepared formulas were tested for their in-vitro physicochemical properties and an ex-vivo intestinal permeability study was conducted
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Schedule a callMore From: Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512)
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