Enhanced permeation of diazepam through artificial membranes from supersaturated solutions.
The present work consists of studies of saturated and supersaturated solutions of diazepam (DZP) in [glycofurol (GF)/water] cosolvent systems, which are a potential dosage form for intranasal administration of DZP in rapid response to epileptic seizure emergencies. Equilibrium solubility of DZP increased in a convex manner with GF content, and also increased with temperature. Rapidly mixed supersaturated 40 mg/mL solutions displayed temporal stability, with long periods before onset of crystallization. Permeation of supersaturated DZP across polydimethylsiloxane (PDMS) membranes, chosen as an in vitro model for nasal mucosa, was shown to be well described by Theeuwes's transference equation, when DZP was formulated up to three times its solubility in a particular cosolvent vehicle. Transference and time lag were independent of vehicle composition, indicating that permeation enhancement was due virtually exclusively to enhanced driving force due to supersaturation. Implications of these results on potential intranasal DZP delivery systems based on supersaturation are discussed.[1]References
- Enhanced permeation of diazepam through artificial membranes from supersaturated solutions. Hou, H., Siegel, R.A. Journal of pharmaceutical sciences. (2006) [Pubmed]
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