Preparation and In Vivo Evaluation of a Lidocaine Self-Nanoemulsifying Ointment with Glycerol Monostearate for Local Delivery.

Ji-Hyun Kang,Chun-Woong Park,Dong-Wook Kim,Kwang-Hwi Yoo,Hyo-Young Park,Seung-Min Hyun,Sang-Duk Han

doi:10.3390/pharmaceutics13091468

Ji-Hyun Kang, Chun-Woong Park + Show 5 more

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https://doi.org/10.3390/pharmaceutics13091468

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Abstract

Lidocaine, a commonly used local anesthetic, has recently been developed into a number of ointment products to treat hemorrhoids. This study examined its efficient delivery to the dermis through the pharmaceutical improvement of hemorrhoid treatment ointments. We attempted to increase the amount of skin deposition of lidocaine by forming a nanoemulsion through the self-nanoemulsifying effect that occurs when glycerol monostearate (GMS) is saturated with water. Using Raman mapping, the depth of penetration of lidocaine was visualized and confirmed, and the local anesthetic effect was evaluated via an in vivo tail-flick test. Evaluation of the physicochemical properties confirmed that lidocaine was amorphous and evenly dispersed in the ointment. The in vitro dissolution test confirmed that the nanoemulsifying effect of GMS accelerated the release of the drug from the ointment. At a specific concentration of GMS, lidocaine penetrated deeper into the dermis; the in vitro permeation test showed similar results. When compared with reference product A in the tail-flick test, the L5 and L6 compounds containing GMS had a significantly higher anesthetic effect. Altogether, the self-nanoemulsifying effect of GMS accelerated the release of lidocaine from the ointment. The compound with 5% GMS, the lowest concentration that saturated the dermis, was deemed most appropriate.

Highlights

IntroductionHemorrhoid disease is the third leading outpatient gastrointestinal diagnosis, accounting for 3.3 million office and emergency department visits in the United States [1]
Hemorrhoid disease is the third leading outpatient gastrointestinal diagnosis, accounting for 3.3 million office and emergency department visits in the United States [1].The self-reported incidence of hemorrhoids in the United States is 10 million per year, corresponding to 4.4% of the population [2,3,4]
L3 had a droplet size at a 1:2 dilution of 108 nm and a polydispersity index (PDI)

Summary

Introduction

Hemorrhoid disease is the third leading outpatient gastrointestinal diagnosis, accounting for 3.3 million office and emergency department visits in the United States [1]. The self-reported incidence of hemorrhoids in the United States is 10 million per year, corresponding to 4.4% of the population [2,3,4]. One important facet of the management of post-hemorrhoidectomy pain is the application of a multimodal pain control strategy [6,7,8]. The procedure-specific post-operative pain management (PROSPECT) working group has released Grade A recommendations for pain management after hemorrhoid surgery, including beyond-conventional oral analgesics, oral diosmin, metronidazole, laxatives, local application of lidocaine, glyceryl trinitrate, cholestyramine ointments, and infiltration with long-acting local anesthetics [9,10]

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