Nasal mucoadhesive delivery systems of the anti-parkinsonian drug, apomorphine: influence of drug-loading on in vitro and in vivo release in rabbits

Lyophilized polyacrylic acid powder formulations loaded with apomorphine HC l were prepared and the influence of drug loading on in vitro release and i n vivo absorption studied after intranasal administration in rabbits. These formulations prepared with Carbopol 971P, Carbopol 974P and polycarbophil sustained apomorphine release both in vitro and in vivo. The in vitro relea se rate and mechanism were both influenced by the drug loading: There was n o large influence of drug loading on the time to achieve the peak (T-max) f or a particular polymer, but T-max differed between different polymers. For a particular drug loading, the T-max from Carbopol 971P was the slowest co mpared with that for Carbopol 974P and polycarbophil; however, only-the T-m ax from Carbopol 971P loaded with 15% w/w of apomorphine was significantly longer than polycarbophil of similar drug loading (P= 0.0386). The trend fu rther observed was that increasing drug loading led to increased peak plasm a concentration and area under the curve (AUC). In the second part of this study, a mixture containing an immediate release component and sustained re lease formulation was administered in an attempt to increase the initial pl asma level, as this could be therapeutically beneficial. Only one peak plas ma concentration was observed and the initial plasma concentrations were no higher than those obtained with solely sustained release formulation. The T-max, the peak plasma drug concentration (C-max) and AUC from the lactose- containing formulation were lower than the formulation without lactose but the differences were only marginally statistically significant for C-max (P = 0.0911) and AUC (P = 0.0668), but not T-max (P = 0.2788). (C) 1999 Publi shed by Elsevier Science B.V. All rights reserved.