The overall objective of this study was to develop pluronic F127 (PF127)-containing formulations of pilocarpine hydrochloride (PHCL) suitable for controlled-release ocular delivery of PHCL. Various aqueous formulations were evaluated containing 1% w/v PHCL and 25% w/v PF127 alone or with one of the following additives present: poly(ethylene glycol) 4600 (PEG), poly(vinylpyrrolidone) 10,000 (PVP), poly(vinyl alcohol) 10,000 (PVA), methylcellulose 15 cP (MC), and hydroxypropyl methylcellulose 80-120 cP (HPMC). The in vitro dissolution of the PF127 formulations and the pilocarpine release profiles from them were obtained simultaneously at 34 degrees C and room temperature using a membraneless in vitro model. It was observed that the PEG- and PVP-containing PF127 formulations of PHCL dissolved the quickest and released the drug at a significantly faster rate than the control PF127 formulation, which had no additive present. The PF127 formulations of PHCL containing MC or HPMC exhibited the slowest dissolution rates and released the drug the slowest. The same rank order was observed at each temperature for the dissolution and PHCL release profiles of each formulation. On the basis of the in vitro results, the PF127 formulations of PHCL containing MC or HPMC as an additive showed potential for use as controlled-release ocular delivery systems for PHCL.

The overall objective of this study was to develop Pluronic F127 (PF127)-containing formulations of pilocarpine hydrochloride (PHCL) which can be used for sustained-release ocular delivery of PHCL. The PF127 formulations of PHCL containing methylcellulose (MC) or hydroxypropyl methylcellulose (HPMC) as an additive had previously exhibited the slowest dissolution rates and released the drug the slowest in vitro. This study was performed to assess the in vivo performance of these two formulations using miosis in the albino rabbit eye produced by PHCL as a measure of ocular bioavailability. The PF127MC formulation (20 microL) had a significantly greater intensity of miosis compared to the same volume of an isotonic solution of PHCL. The duration and the intensity of the miotic response increased significantly as the instilled volume of the PF127MC gel formulation increased. The miotic response, expressed as % bioactivity by assigning a value of 100% to the 20 microL PF127MC treatment, was increased as the volume instilled was reduced from 60 to 20 microL. However, no difference in bioactivity between the 60 and 100 microL volumes was observed. In addition, the 100 microL volumes of both the PF127MC and PF127HPMC gel formulations exhibited bioactivity equivalent to 20 microL of an isotonic PHCL solution. Thus, for a given instilled concentration, the larger the volume instilled the greater the amount of drug present in tear fluid and thus the higher the concentration 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 formulations of PHCL having MC or HPMC as an additive showed considerable potential as sustained-release ocular delivery systems for PHCL. This conclusion was based upon their ability to provide a substantial prolongation of drug action and an improvement in the ocular bioavailability of pilocarpine compared to conventional eye drops and previously utilized PF127 formulations of PHCL. It appears that ocular bioavailability can be increased more readily by altering both the rheological characteristics of the delivery system and by using a smaller dose volume.

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The objectives of our study were to prepare a biodegradable polyisobutylcyanoacrylate (PIBCA) colloidal particulate system of pilocarpine, to incorporate it into a Pluronic F127(PF127)-based gel delivery system, and to evaluate its ability to prolong the release of pilocarpine. Polyisobutylcyanoacrylate nanocapsules (PIBCA-NC) of pilocarpine were prepared by interfacial polymerization. Physicochemical characterization of the colloidal dispersion of PIBCA-NC of pilocarpine was performed by measuring drug loading, particle size analysis, and scanning electron microscopy. Results indicated that approximately 13.5% of pilocarpine was loaded onto the PIBCA-NC, the nanocapsules ranged from 370 to 460 nm, the distribution was narrow, and there was no significant effect of stirring speed on particle size. The PIBCA-NC dispersion of 1% pilocarpine alone (I) and after incorporation into the Pluronic F127 gel delivery system (II) were compared against 1% pilocarpine incorporated into a PF127 gel containing 5% methylcellulose (PF127MC) alone (III) by measuring the miotic response in the albino rabbit eye. Statistical analysis indicated a rank-order for both the duration and intensity of miosis of II > III >> I, with all differences being significant (p < 0.05). Thus, it appears that II increases the contact time of pilocarpine with the absorbing tissue in the eye, thereby improving ocular bioavailability. The PIBCA-NC of pilocarpine dispersed in the PF127MC gel delivery system has considerable potential for achieving a prolonged delivery for such drugs as pilocarpine and other more hydrophobic drugs.