International Journal of Pharmaceutical Investigation, 2016, 6, 3, 148-157.
Published: August 2016
Type: Original Article
Department of Pharmaceutics, Vaagdevi College of Pharmacy, Hanamkonda, Warangal, Telangana, India.
Department of Pharmaceutics, Institute of Pharmaceutical Technology, Sri Padmavathi Mahila University, Tirupathi, Andhra Pradesh, India.
Department of Pharmaceutics, Mother Teresa College of Pharmacy, Hyderabad, Telangana, India.
Faculty of Pharmacy, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, India.
Objective: The objective of the present work was to prepare and evaluate a novel oral formulation for systemic delivery of low molecular weight heparin (LMWH). The formulation consisted of Eudragit S 100-coated positively charged liposomes encapsulating LMWH and a penetration enhancer. Materials and Methods: Positively charged liposomes were first prepared by the thin film hydration method using lipid (soy phosphotidylcholine and cholesterol) and stearyl amine (SA) in the optimum ratio of 16:1, along with cetylpyridinium chloride (CPC) as a penetration enhancer. Prepared liposomes were coated with negatively charged Eudragit S 100 (0.3% w/v). The formulations were studied for various in vitro and in vivo properties. Differential scanning calorimetry (DSC), x-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) studies, and in vitro drug release were used for in vitro characterization of the formulations. Ex vivo permeation studies were performed by using distal small intestine of rat. Oral absorption studies were conducted with the rat model. Results: Coating of the liposomes was confirmed by SEM and particle size determination studies. In vitro release studies of coated liposomes have demonstrated that the release of LMWH was in the following order: Stomach < small intestine < distal small intestine < colon. Ex vivo permeation studies have shown a fivefold increase in permeation of LMWH with Eudragit S 100-coated liposomes compared to uncoated, uncharged liposomes. Oral absorption studies have showed that with Eudragit-coated liposomes, the oral bioavailability of LMWH was improved, compared to plain LMWH solution. This is revealed by a threefold increase in the area under the curve (AUC) of the plasma concentration time curve. Conclusion: A novel formulation for oral delivery of LMWH was thus successfully prepared and evaluated.
Keywords: Colon targeting, Eudragit S 100, Liposomes, Low molecular weight heparin (LMWH), Oral absorption, Permeation .