The Ocular Pharmacokinetics and Bioavailability of Puerarin in the Microemulsion With Ion-Triggered in situ Gelling Ophthalmic Delivery System

Abstract

Purpose: : To evaluate the ocular pharmacokintics and conreal penetration of puerarin (PU) after topical application of an ophthalmic solution based on microemulsion with ion-triggered in situ gelling system for puerarin, which is an osajin isoflavone extracted from radix of Pueraria lobata and poorly soluble in water.

Methods: : A microemulsion containing ion-triggered in situ gelling vehicle for ophthalmic delivery of 1% PU (ME-G-PU) and a microemulsion containing 1% PU (ME-PU) with the same pH (5.6) were prepared, respectively. PU solution containing polyvinyl pyrrolidone (PVP-PU) with the same pH was prepared as a control. A single dose of ME-G-PU, ME-PU or PVP-PU was applied to rabbits. Aqueous humor and cornea were collected after application at 5, 15, 30, 60, 120, 180, 240, 360and 480 min. PU concentrations were determined by HPLC with a fluorescence detector after extraction.

Results: : After topically applying ME-G-PU, the PU levels in aqueous humor were significantly increased at 5~480min compared with those of ME-PU and PVP-PU at the corresponding time points (p < 0.05) excluding with that of PVP-PU at 360 min. The highest levels of PU in aqueous humor (C_max, 689.34 ± 449.42ng/mL) were obtained after 60 min application of ME-G-PU, The area under the concentration-time in aqueous humor over 480min (AUC_0-480) for ME-G-PU was increased compared with ME-PU and PVP-PU (108162.3ng/mL•min vs 14638.5 and 36635.5 ng/mL•min). The ME-G-PU produced an over seven-fold and three-fold bioavailability (AUC_0-120) increase in aqueous humors over the ME-PU and PVP-PU, respectively. Peak PU concentration in cornea (92932.40 ± 6992.15 ng/g) was achieved within 5 min after instillation of ME-G-PU, the PU levels in cornea were significantly increased at 5~180min compared with those of ME-PU and PVP-PU at the corresponding time points (p < 0.05). The AUC_0-480 in cornea for ME-G-PU was increased compared with ME-PU and PVP-PU (599901.0 ng/g•min, 190967.5 and 215346.7 ng/g•min). The ME-G-PU produced an over three-fold bioavailability (AUC_0-120) increase in corneas over the ME-PU and PVP-PU, respectively.

Conclusions: : ME-G-PU is superior to ME-PU and PVP-PU by increasing ocular bioavailability.

Keywords: cornea: basic science • drug toxicity/drug effects