Abstract
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.
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