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 HCl were prepared and the influence of drug loading on in vitro release and in 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 release rate and mechanism were both influenced by the drug loading. There was no large influence of drug loading on the time to achieve the peak (Tmax) for a particular polymer, but Tmax differed between different polymers. For a particular drug loading, the Tmax from Carbopol 971P was the slowest compared with that for Carbopol 974P and polycarbophil; however, only the Tmax from Carbopol 971P loaded with 15% w/w of apomorphine was significantly longer than polycarbophil of similar drug loading (P=0.0386). The trend further observed was that increasing drug loading led to increased peak plasma concentration and area under the curve (AUC). In the second part of this study, a mixture containing an immediate release component and sustained release formulation was administered in an attempt to increase the initial plasma level, as this could be therapeutically beneficial. Only one peak plasma concentration was observed and the initial plasma concentrations were no higher than those obtained with solely sustained release formulation. The Tmax, the peak plasma drug concentration (Cmax) and AUC from the lactose-containing formulation were lower than the formulation without lactose but the differences were only marginally statistically significant for Cmax (P=0.0911) and AUC (P=0.0668), but not Tmax (P=0.2788).
Ikechukwu Ugwoke
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M
Laboratorium voor Farmacotechnologie en Biofarmacie, Campus Gasthuisberg O&N, Katholieke Universiteit Leuven, B-3000, Leuven, Belgium.
Sam
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E
Van Den Mooter
G
G
Verbeke
N
N
Kinget
R
R
D000042:Absorption; D000179:Acrylates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000180:Acrylic Resins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000268:Adhesiveness; D000281:Administration, Intranasal; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001058:Apomorphine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005079:Excipients / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism*; D011817:Rabbits
D000179:Acrylates; D000180:Acrylic Resins; D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D005079:Excipients; C117167:carbopol 974P NF; C030312:calcium polycarbophil; D001058:Apomorphine