Intranasal bioavailability of apomorphine from carboxymethylcellulose-based drug delivery systems

Carboxymethyl cellulose (CMC) powder formulation of apomorphine was prepare d by lyophilization and characterized with respect to the in vitro and intr anasal in vivo release of apomorphine in rabbits. This was compared to apom orphine release from degradable starch microspheres (DSM) and lactose, as w ell as in vivo absorption after subcutaneous injection. In vitro apomorphin e release from CMC was sustained, unlike that of DSM and lactose. Changing the drug loading of CMC From 15 to 30% (w/w) influenced drug release rate, which increased with increased drug loading. In vivo absorption of apomorph ine from lactose, DSM and subcutaneous injection were rapid and not sustain ed. Slower absorption rates of apomorphine occurred from CMC. The fastest a bsorption rate was obtained with lactose and the slowest with CMC of 15% (w /w) drug loading. The T-max from the CMC dosage Forms were significantly pr olonged compared to the immediate release for ms. Plasma drug levels were s ustained with CMC. The plasma concentration was maintained within 50% of th e C-max, longer (15% (w/w), 70 min; 30% (w/w), 40 min) compared to the rest (lactose, 20 min; DSM, 25 min, subcutaneous injection, 35 min). The sustai ned plasma level of apomorphine by CMC was achieved with relative bioavaila bilities equivalent to subcutaneous injection. (C) 2000 Elsevier Science B. V. All lights reserved.