Oral delivery of low molecular weight heparin microspheres prepared using biodegradable polymer matrix system.
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.
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, Atlanta, GA 30341, USA.
Satya Surya Shankar
SS
Lanke
Sanjay G
SG
Gayakwad
James Grady
JG
Strom
Martin J
MJ
D'souza
D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000097:blood; D002152:Calorimetry, Differential Scanning; D016503:Drug Delivery Systems; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D008863:Microspheres; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013608:Tablets, Enteric-Coated / Q000008:administration & dosage / Q000737:chemistry
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D011108:Polymers; D013608:Tablets, Enteric-Coated