CONTROLLED-RELEASE AND DURA-MATER PERMEABILITY OF LIDOCAINE AND IBUPROFEN FROM INJECTABLE POLOXAMER-BASED GELS

Epidural administration of drugs is becoming more common in the treatm ent of severe forms of pain. To improve present therapies, a long-acti ng single-dose gel injection would be beneficial. The present study in vestigated the use of three different polymers as additives in injecta ble poloxamer gel in controlling the drug release. The release of lido caine . HCl and ibuprofen Na from 25% poloxamer (PO) gel and poloxamer gel with hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcel lulose (CMC), or dextran (DE) was studied in vitro. Cellulose additive s significantly prolonged ibuprofen release, whereas additives were fo und to have a slight release-increasing effect on lidocaine as compare d with the PO gel. The structural differences of the gels, more than t he macroviscosity, seem to regulate the release of drugs. The drug per meation-prolonging effect of the respective gels, along with the contr ol solutions, was evaluated in vitro using porcine dura mater membrane . The compact gel depot acted as the rate-limiting step, and significa ntly prolonged the dural permeation of both drugs in comparison with c ontrol solutions. The difference in the drug release and permeation-re ducing effects of the gels demonstrated the possibility for interactio ns between dural membrane and the gel. The findings are promising for further experimental in vivo animal testing of these injectable poloxa mer-based gels. (C) 1998 Elsevier Science B.V.