Formulation of controlled release ocular delivery systems of pilocarpine.

摘要

The main objective of this work was to develop Poloxamer 407 (Pluronic F127)-based formulations for controlled ocular delivery of pilocarpine as a model drug. Various additives such as polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC), were incorporated into formulations containing 25% PF127, 1% pilocarpine hydrochloride (PHCL) alone or containing one of the additives. The release of PHCL from the PF127 formulations and the dissolution profile of the formulations are obtained simultaneously at RT and 34°C. The formulations with 25% PF127, 1% PHCL and either 5% MC or 3% HPMC showed the slowest dissolution and also released the drug the slowest of the formulations evaluated in vitro. The PHCL release from the two formulations exhibited a zero-order release and the mechanism of PHCL release seem to be dissolution controlled. Therefore the MC- and HPMC-containing PF127 formulations of PHCL were selected for further in-vivo studies. The miotic response to equal administered volumes of an isotonic solution of 1% PHCL and the MC-containing PF127 formulation of PHCL was measured. The PF127 formulation showed a statistically significant increase in the duration of miosis and the intensity of the miotic response (i.e., higher ocular bioavailability) compared to the same instilled volume of the Isotonic PHCL solution. In the next phase of this work pilocarpine-incorporated polyisobutylcyanoacrylate nanocapsules (PIBCA-NC) were prepared, characterized in vitro and evaluated in vivo in albino rabbit eyes. Here the PIBCA-NC of PHCL containing 1% pilocarpine, of which about 13.5% was incorporated into the nanocapsules, were administered alone or using the aforementioned MC-containing PF127 formulation with 25% PF127 and 5% MC as a vehicle. The in vivo results indicated that the PIBCA-NC dispersion of 1% pilocarpine, when administered using the MC-containing PF127 gel vehicle, significantly improved the duration and the intensity of the miotic response compared to the administration of the same volume of the PIBCA-NC dispersion of 1% pilocarpine alone. Therefore, the PF127 formulations of pilocarpine developed and evaluated thus far, offer considerable promise in terms of their potential to be used for the controlled release ocular delivery of pilocarpine.