EVALUATION OF PLURONIC F127-BASED SUSTAINED-RELEASE OCULAR DELIVERY SYSTEMS FOR PILOCARPINE USING THE ALBINO RABBIT EYE MODEL

The overall objective of this study was to develop Pluronic F127 (PF12 7)-containing formulations of pilocarpine hydrochloride (PHCL) which c an be used for sustained-release ocular delivery of PHCL. The PF127 fo rmulations of PHCL containing methylcellulose (MC) or hydroxypropyl me thylcellulose (HPMC) as an additive had previously exhibited the slowe st dissolution rates and released the drug the slowest in vitro. This study was performed to assess the in vivo performance of these two for mulations using miosis in the albino rabbit eye produced by PHCL as a measure of ocular bioavailability. The PF127MC formulation (20 mu L) h ad a significantly greater intensity of miosis compared to the same vo lume of an isotonic solution of PHCL. The duration and the intensity o f the miotic response increased significantly as the instilled volume of the PF127MC gel formulation increased. The miotic response, express ed as % bioactivity by assigning a value of 100% to the 20 mu L PF127M C treatment, was increased as the volume instilled was reduced from 60 to 20 mu L. However, no difference in bioactivity between the 60 and 100 mu L volumes was observed. In addition, the 100 mu L volumes of bo th the PF127MC and PF127HPMC gel formulations exhibited bioactivity eq uivalent to 20 mu L of an isotonic PHCL solution. Thus, for a given in stilled concentration, the larger the volume instilled the greater the amount of drug present in tear fluid and thus the higher the concentr ation delivered to the iris sphincter muscle and hence the greater the miotic response. However, the fraction of the dose reaching the iris sphincter muscle was greater for the smaller instilled volume. On the basis of these findings and previous in vitro results, the PF127 formu lations of PHCL having MC or HPMC as an additive showed considerable p otential as sustained-release ocular delivery systems for PHCL. This c onclusion was based upon their ability to provide a substantial prolon gation of drug action and an improvement in the ocular bioavailability of pilocarpine compared to conventional eye drops and previously util ized PF127 formulations of PHCL. It appears that ocular bioavailabilit y can be increased more readily by altering both the rheological chara cteristics of the delivery system and by using a smaller dose volume.