Evaluation of Pluronic F127-Based Sustained-Release Ocular Delivery Systems for Pilocarpine using the Albino Rabbit Eye Model

Abstract

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.

A Nonionic Surfactant/Chitosan Micelle System in an Innovative Eye Drop Formulation

“…The BF1 and BF4 formulations presented surface tension values of 38-39 mN m À1 at 348C (the temperature of the ocular surface), 23 which are similar to those of normal tears (40-50 mN m À1 ). 34 No ocular damage or clinically abnormal signs were observed in the cornea, conjunctiva or iris. Only grades 0 and occasionally 1 were recorded, and no differences between the control and treated eyes for each group of rabbits were observed.…”

A Review of Poloxamer 407 Pharmaceutical and Pharmacological Characteristics

“…The reduction of the volume (e.g., 20 ml instead of 60Y100 ml) administrated in the eyes generally improved the AUC. Indeed, limitation of reflex tearing reduces lachrymal drainage and thus favours drug residence in the pre-ocular structure (82).…”

Delivery of Flt3 ligand (Flt3L) using a poloxamer-based formulation increases biological activity in mice

“…9 The combination of Poloxamer-407 and HPMC provides a drug delivery matrix with slower drug release compared to either component alone. 10,21,25,26 In the present studies, we examined the mobilization properties of Flt3L when formulated in a sustained release matrix composed of Poloxamer-407 and HPMC. Our pharmacokinetic analyses demonstrated that the administration of Flt3L formulated with PG (PG-Flt3L) resulted in sustained delivery.…”