SELF-MICRO EMULSIFYING DRUG DELIVERY SYSTEM OF URSOLIC ACID: FORMULATION DEVELOPMENT, CHARACTERIZATION, PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES FOR DIABETIC COMPLICATIONS

Golla Chandra Mouli,Ciddi Veeresham

doi:10.22159/ijap.2022v14i2.43692

Abstract

Objective: The objective of this study was to develop, characterize, and conduct pharmacokinetic and pharmacodynamic studies on ursolic acid solid self microemulsifying drug delivery system (UA-S-SMEDDS) for the treatment of diabetic complications. Methods: Liquid self microemulsifying drug delivery system (L-SMEDDS) were made with Capryol 90 as an oil, Cremophor EL as a surfactant, and polyethylene glycol (PEG) 400 as a co-surfactant. The surfactant and co-surfactant (Smix) ratios were calculated using a pseudo ternary phase diagram. At different pH levels and with water, the globule size, polydispersity index (PDI), zeta potential (ZP), and dilution were all assessed. S-SMEDDS has developed adsorption to a solid carrier by utilizing L-SMEEDS formulation. The powder properties, liquid retention potential, globule size, PDI, ZP, assay, and pharmacokinetic studies were all evaluated. The pharmacodynamic investigations of the S-SMEDDS formulation in streptozotocin (STZ) induced Wistar rats were evaluated using malondialdehyde (MDA) and glutathione (GSH) determination in tissues and section studies. Results: S-SMEDDS formulation was successfully developed with a droplet size of 163.4±1.475 nm, PDI of 0.251±0.042, a ZP of-21.3±1.02, an assay of 96.21±0.75%. The release studies showed 26.28% (0.1N HCl) and 83.57% (6.8 phosphate buffer) were released in 15 min. When comparing the pharmacokinetics of a UA-loaded S-SMEDDS to the coarse suspension, the S-SMEDDS (F2A) showed a 4.12 fold improvement in UA oral bioavailability. The pharmacodynamic results showed that S-SMEDDS was a higher recovery rate. Conclusion: The developed solid SMEDDS (F2A) formulation proved effective in treating diabetic complications in STZ induced Wistar rats by inhibiting the aldose reductase enzyme.

Highlights

Ursolic acid (UA) is a pentacyclic triterpene that can be found in a variety of herbal remedies [1]
The vehicles in a self-micro emulsifying drug delivery system (SMEDDS) formulation have a high solubilization capacity, ensuring that the drug is completely dissolved, with the results reported in table 1
When comparing SSMEDDS (F2A) to ursolic acid coarse suspension, the reduction in blood glucose level was greater with the formulation of S-SMEDDS (F2A). These findings show that optimized S-SMEDDS (F2A) have a pronounced hypoglycemic effect in diabetic rats

Summary

Introduction

Ursolic acid (UA) is a pentacyclic triterpene that can be found in a variety of herbal remedies [1]. Antimicrobial, anti-inflammatory, anti-tumor, enhanced hair growth, melanocyte proliferation, antidiabetes, and anti-obesity are some of the biological effects of UA [2]. In the intestine, it is absorbed through passive diffusion. It's a P-gp substrate that can be related to the efflux of a drug transporter [3]. To increase the biopharmaceutical features of UA, many drug delivery techniques have been devised. UA formulations have been successfully manufactured using a variety of delivery techniques, including nano-emulsions, nanoparticles, liposomes, cocrystals, and solid dispersions [5-9]

Methods

Results

Conclusion