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

• Published in: International journal of pharmaceutics Vol. 181; no. 1; pp. 125 - 138
• Main Authors: Ugwoke, Michael Ikechukwu, Sam, Exaud, Van Den Mooter, Guy, Verbeke, Norbert, Kinget, Renaat
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 20.04.1999; Elsevier
• Subjects: Absorption; Acrylates - administration & dosage; Acrylates - pharmacokinetics; Acrylic Resins - administration & dosage; Acrylic Resins - pharmacokinetics; Adhesiveness; Administration, Intranasal; Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; Antiparkinson Agents - administration & dosage; Antiparkinson Agents - blood; Antiparkinson Agents - pharmacokinetics; Apomorphine; Apomorphine - administration & dosage; Apomorphine - blood; Apomorphine - pharmacokinetics; Area Under Curve; Biological and medical sciences; Carbopol; Chemistry, Pharmaceutical; Controlled release; Delayed-Action Preparations; Drug Delivery Systems; Excipients - administration & dosage; Excipients - pharmacokinetics; General pharmacology; Male; Medical sciences; Nasal drug delivery; Nasal Mucosa - metabolism; Neuropharmacology; Parkinson’s disease; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polycarbophil; Rabbits; Carbopol; Nasal drug delivery; Polycarbophil; Apomorphine; Parkinson’s disease; Controlled release; Rabbit; Parkinson disease; Powder; Absorption; Degenerative disease; Bioadhesive system; Release; Nervous system diseases; Pharmaceutical technology; Controlled release form; Intranasal administration; Bioavailability; Lagomorpha; Antiparkinson agent; In vitro; Cerebral disorder; In vivo; Vertebrata; Mammalia; Animal; Central nervous system disease; Acrylic acid polymer; Dosage form; Active ingredient; Pharmacokinetics; Extrapyramidal syndrome
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(99)00018-6

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 ( T max) for a particular polymer, but T max differed between different polymers. For a particular drug loading, the T max from Carbopol 971P was the slowest compared with that for Carbopol 974P and polycarbophil; however, only the T max 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 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).