Preparation and evaluation of a novel oral delivery system for low molecular weight heparin.
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.


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.


CONCLUSIONS
A novel formulation for oral delivery of LMWH was thus successfully prepared and evaluated.
Department of Pharmaceutics, Vaagdevi College of Pharmacy, Hanamkonda, Warangal, Telangana, India.
Nallaguntla
N
Lavanya
Department of Pharmaceutics, Institute of Pharmaceutical Technology, Sri Padmavathi Mahila University, Tirupathi, Andhra Pradesh, India.
Yallamalli Indira
YI
Muzib
Department of Pharmaceutics, Mother Teresa College of Pharmacy, Hyderabad, Telangana, India.
Jithan
J
Aukunuru
Faculty of Pharmacy, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, India.
Umamahesh
U
Balekari
Colon targeting; Eudragit S 100; liposomes; low molecular weight heparin (LMWH); oral absorption; permeation