Assessment of the in vitro transport parameters for ethanehydroxy diphosphonate through a polyurethane membrane. A potential refillable reservoir drug delivery device.
Calcification (CALC) is the most frequent cause of failure in bioprosthetic heart valves (BHV) fabricated from glutaraldehyde pretreated porcine aortic valve or bovine pericardium. Site specific controlled administration of ethanehydroxy diphosphonate (EHDP), using numerous carriers, has been successful in inhibiting CALC of BHV tissue in an accelerated rat subdermal model, without adverse effects on serum calcium, bone development, or overall somatic growth. The current study was designed to evaluate refillable reservoir devices fabricated from polyurethane (Biomer Woburn, MA) with regard to their transport properties relative to EHDP. The refillable reservoirs were evaluated for EHDP release in vitro at 22 degrees C (under perfect sink conditions) into both a physiologic receptor phase (N-2 hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffer, pH = 7.4) with (1.5 mM) or without Ca2+ present. Transport parameters for EHDP diffusion through the polyurethane membranes used to fabricate the reservoirs were significantly different for the two receptor phases evaluated. The mean diffusion coefficients (D) for EHDP through the polyurethane membrane into each receptor phase were not significantly different. However, an approximately 3.5-fold reduction was observed in the mean value of the partition coefficient (K) for EHDP when EHDP was evaluated for release into a receptor phase that contained 1.5 mM Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)
Johnston
T P
TP
Department of Pharmaceutics, College of Pharmacy, University of Illinois, Chicago 60612.
Webb
C L
CL
Schoen
F J
FJ
Levy
R J
RJ
D000818:Animals; D001705:Bioprosthesis / Q000009:adverse effects; D002114:Calcinosis / Q000517:prevention & control; D004058:Diffusion; D012968:Etidronic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005069:Evaluation Studies as Topic; D006350:Heart Valve Prosthesis / Q000009:adverse effects; D066298:In Vitro Techniques; D015918:Infusion Pumps, Implantable; D007700:Kinetics; D008567:Membranes, Artificial; D011140:Polyurethanes
D008567:Membranes, Artificial; D011140:Polyurethanes; D012968:Etidronic Acid