Controlled release injectable liposomal gel of ibuprofen for epidural analgesia.
The epidural administration is used commonly in the treatment of pain. Nonsteroidal anti-inflammatory drugs, especially ibuprofen, would have potential in epidural use. Like many epidurally useful drugs it, however, has a short duration of action, which is a limiting factor. To improve epidural pain treatment, a long-acting, single-dose gel injection is being developed. In the present study, the possibility of using liposomal systems to control the release and dural permeation of ibuprofen was investigated in vitro. Liposomal solutions of ibuprofen.Na (20 mg/ml) were prepared by high-pressure homogenization from egg phosphatidylcholine. The liposomal gel consisted of poloxamer 407 and the liposomal solution. No signs in the 1H-NMR spectroscopy of line broadenings or chemical shifts were observed. The liposomal formulations were reproducible and stable. Ibuprofen release in phosphate buffer, pH 7.4, at 37 degrees C from the liposomal solution and the liposomal gel were prolonged significantly compared with their respective solution and gel controls. The liposomal gel controlled ibuprofen release and dural permeation in vitro and showed a permeation pattern favourable for maintaining constant drug levels. The liposomal poloxamer gel represents a new formulation approach to increase the local epidural availability of ibuprofen. It appeared to be a promising injectable controlled-release drug delivery system.
Paavola
A
A
Department of Pharmacy, Pharmaceutical Technology Division, Biocenter 2, PO Box 56, University of Helsinki, Helsinki, Finland. anne.paavola@helsinki.fi
Kilpeläinen
I
I
Yliruusi
J
J
Rosenberg
P
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000378:metabolism; D004337:Drug Carriers; D004355:Drug Stability; D004388:Dura Mater / Q000378:metabolism; D005782:Gels; D007052:Ibuprofen / Q000737:chemistry* / Q000378:metabolism; D066298:In Vitro Techniques; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D010539:Permeability; D010713:Phosphatidylcholines; D020442:Poloxamer; D012995:Solubility; D013552:Swine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D005782:Gels; D008081:Liposomes; D010713:Phosphatidylcholines; D020442:Poloxamer; D007052:Ibuprofen