In vitro characterization and in vivo performance of mefenamic acid-sodium diethyldithiocarbamate based liposomes

Qais Bashir Jarrar,Zainul Amiruddin Zakaria,Muhammad Nazrul Hakim,Manraj Singh Cheema

doi:10.1590/s2175-97902019000117870

Qais Bashir Jarrar, Zainul Amiruddin Zakaria + Show 2 more

Open Access

https://doi.org/10.1590/s2175-97902019000117870

Copy DOI

Abstract

Mefenamic acid (MFA) is a hydrophobic drug with low dissolution rate. This study aimed to develop stable and reproducible aqueous formulations of MFA using liposomes as drug carriers. The drug entrapment, particles size and drug release profiles, and stability and reproducibility of the liposomes were determined. In addition, the maximum tolerated dose (MTD) was determined in rats via the oral and intraperitoneal routes of administration. Also, the anti-inflammatory efficacy of these liposomes was evaluated using carrageenan-induced paw edema model in rats. MFA-DDC based liposomes demonstrated a drug entrapment efficacy of 93.6%, particles size of 170.9 nm, and polydispersity index of 0.24 which were not statistically affected when stored in room and refrigerated temperatures for at least 4 weeks. The MTD of the intraperitoneally administrated MFA-loaded liposomes was 20 mg MFA/kg, whereas for those of oral administrations, it was up to 80 mg MFA/kg. Intraperitoneal dose (80 mg MFA/kg) of MFA-DDC liposomes induced extrapyramidal symptoms associated with significant elevation in serum potassium and muscle enzymes. Moreover, significant inhibition of paw edema was demonstrated by the oral and intraperitoneal routes. These findings suggest that MFA-DDC based liposomes are an effective formulation of MFA and recommend the use of bioequivalence assessments with commercial formulations.

Highlights

Mefenamic acid (MFA) is a member of NSAIDs which poses anti-inflammatory, anti-nociceptive, and antipyretic properties (Cimolai, 2013)
A drug solution was prepared by dissolving an equivalent amount of MFA and diethyl dithiocarbamate (DDC) (100 mg each) in dimethyl sulfoxide (DMSO)
A simple, rapid, effective, and cost-saving method was developed for MFA detection and quantification in liposomal preparations

Summary

Introduction

Mefenamic acid (MFA) is a member of NSAIDs which poses anti-inflammatory, anti-nociceptive, and antipyretic properties (Cimolai, 2013). According to the biopharmaceutical classification system, this drug belongs to class II drugs which are characterized by poor water solubility and low dissolution rate (Abdul Mudalip et al, 2013). Considerable efforts have been given to enhance MFA water solubility as a key element in improving its bioavailability with little progress (Abdul Mudalip et al, 2013; Imai et al, 1991). Liposomes are drug nanocarriers which basically consist of phospholipids bilayer (s) and pose amphiphilic nature that allows entrapping both hydrophilic and hydrophobic drugs and exhibits multiple biopharmaceutical functions (Bozzuto, Molinari, 2015). Liposomes can enhance drugs solubility, improve bioavailability, and protect the entrapped drug from enzymatic degradation (Bozzuto, Molinari, 2015; Kim, Kim Lee, 2013). Determining the in vitro characteristics of liposomes constitutes a basic requirement for prediction the in vivo performance of the liposomes and selection

Objectives

Methods

Results

Conclusion