Oral delivery of low molecular weight heparin microspheres prepared using biodegradable polymer matrix system

Abstract

Parenteral route is preferred for low molecular weight heparin (LMWH) due to poor oral bioavailability. Biodegradable formulation components were evaluated for possible interactions between the physical mixtures using differential scanning calorimetry. LMWH and an absorption enhancer papain were encapsulated in bovine serum albumin matrix and four formulations were spray-dried (MS.1, MS.2, MS.3, MS.4). Formulations were evaluated for product yield, particle size, particle charge and encapsulation efficiency. In vitro release assessed in pH 7.2 phosphate buffer saline (PBS) revealed a burst release effect (60%) for all the formulations except MS.1. In vivo studies performed in male Sprague Dawley rats showed an enhancement in drug absorption for the MS.2 and MS.3 formulations because of papain action on paracellular tight junctions. A significant increase in LMWH oral bioavailability was demonstrated by MS.3 (21%), among the formulations encapsulated with papain.

• Bovine serum albumin
• papain
• spray-drying
• microspheres
• encapsulation
• absorption enhancement