The effect of formulation variables on the stability of nebulized aviscumine

The effect of formulation variables on the stability of nebulized aviscumine
12 May 2003
Received 30 October 2002; revised 3 February 2003; accepted 7 February 2003. ; Available online 23 March 2003
Hartwig Steckel, , a, Fadi Eskandara and Klaus Witthohnb
International Journal of Pharmaceutics
Volume 257, Issues 1-2 , 12 May 2003, Pages 181-194
ScienceDirect
a Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University, Gutenbergstr. 76, 24118, Kiel, Germany
b VISCUM AG, Technologiepark Bergisch Gladbach, 51429, Bergisch Gladbach, Germany
Abstract
The pulmonary drug delivery of proteins present an alternative to parenteral and oral administration. Nebulization of aqueous protein solutions is an ideal method for pulmonary application of therapeutic proteins considering the difficulties of their formulation as MDIs or DPIs. This research presents the effect of variable excipients on the stability of freeze-dried aviscumine after reconstitution and nebulization. Formulations containing different lyoprotectants have been lyophilized and reconstituted with isotonic salt solution. The loss of aviscumine activity in the nebulizer reservoir and after nebulization with a PariBoy? air-jet nebulizer, a Multisonic? ultrasonic nebulizer and a Systam? ultrasonic nebulizer was determined by a binding assay. The effect of variable lyoprotectants such as 8% (w/v) Dextran T1, HES130, HES450, HP--CD and 6% (w/v) HES450 plus 2% (w/v) mannitol on the stability of aviscumine to air-jet and ultrasonic nebulization has been evaluated. Only 50% of aviscumine activity was retained after 20 min nebulization, where 8% (w/v) HES450 was shown to be the best stabilizer. Stabilization of aviscumine by the addition of variable surfactants as 0.01 and 0.1% (w/v) Poloxamer 188, 0.03 and 0.1% (w/v) PEG 8000, 0.03 and 0.1% (w/v) Solutol HS15 and 0.03 and 0.1% (w/v) octanoyl-N-methyl-glucamide to the reconstitution solution has also been studied. By the addition of 0.03% (w/v) octanoyl-N-methyl-glucamide, 70% of the activity was retained after 20 min nebulization.
Author Keywords: Nebulizer; Octanoyl-N-methyl-glucamide; Stability of proteins; Lyoprotectants; Aviscumine
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