The addition of calcium ions to starch/Carbopol mixtures enhances the nasal bioavailability of insulin.
To evaluate the influence of calcium poly(acrylates) on the nasal absorption of insulin in rabbits, starch/poly(acrylic acid) (ratio 25/75) (SD 25/75) was neutralised with NaOH and/or Ca(OH)(2). After neutralisation, a mixture of sodium and/or calcium carboxylate was formed depending on the Ca(OH)(2) concentration in the formulation. IR spectroscopy confirmed that most of the calcium molecules in the formulation interacted with acid groups of the acrylic acid polymer. Addition of Ca(OH)(2) to aqueous dispersions containing starch/poly(acrylic acid) yielded powders with an enhanced absorption of insulin after nasal delivery to rabbits in comparison with the equivalent powder without Ca(OH)(2). A mixture of SD 25/75 and Ca(OH)(2) at a ratio of 90/10 neutralised to pH 7.4 with NaOH induced the highest absorption of insulin, obtaining a bioavailability of +/-29% (vs. 19% for an equivalent formulation without Ca(OH)(2)). This increase in nasal delivery was possibly due to a higher elasticity after dispersing this formulation in nasal fluid and to a higher water absorbing capacity. Furthermore, after nasal delivery of (SD 25/75)/Ca(OH)(2) 90/10, a decrease in t(max) was observed, possibly due to a progressive dissociation of Ca(2+)-ions after hydration of the powder resulting in the closing of the tight junctions.
Pringels
E
E
Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
Vervaet
C
C
Verbeeck
R
R
Foreman
P
P
Remon
J P
JP
D000180:Acrylic Resins; D000281:Administration, Intranasal; D000818:Animals; D001682:Biological Availability; D002118:Calcium / Q000008:administration & dosage*; D007328:Insulin / Q000493:pharmacokinetics*; D011145:Polyvinyls / Q000008:administration & dosage*; D011817:Rabbits; D013213:Starch / Q000008:administration & dosage*
D000180:Acrylic Resins; D007328:Insulin; D011145:Polyvinyls; C006912:carboxypolymethylene; D013213:Starch; D002118:Calcium