Liquisolid Systems to Improve the Dissolution of Furosemide

Babatunde Akinlade

doi:10.3797/scipharm.0912-23

Abstract

A liquisolid system has the ability to improve the dissolution properties of poorly water soluble drugs. Liquisolid compacts are flowing and compactable powdered forms of liquid medications. The aim of this study was to enhance the in vitro dissolution properties of the practically water insoluble loop diuretic furosemide, by utilising liquisolid technique. Several liquisolid tablets were prepared using microcrystalline cellulose (Avicel® pH-101) and fumed silica (Cab-O-Sil® M-5) as the carrier and coating materials, respectively. Polyoxy-ethylene-polyoxypropylene-polyoxyethylene block copolymer (Synperonic® PE/L 81); 1,2,3-propanetriol, homopolymer, (9Z)-9-octadecenoate (Caprol® PGE-860) and polyethylene glycol 400 (PEG 400) were used as non- volatile water-miscible liquid vehicles. The liquid loading factors for such liquid vehicles were calculated to obtain the optimum amounts of carrier and coating materials necessary to produce acceptable flowing and compactible powder admixtures viable to produce compacts. The ratio of carrier to coating material was kept constant in all formulations at 20 to 1. The formulated liquisolid tablets were evaluated for post compaction parameters such as weight variation, hardness, drug content uniformity, percentage friability and disintegration time. The in-vitro release characteristics of the drug from tablets formulated by direct compression (as reference) and liquisolid technique, were studied in two different dissolution media. Differential scanning calorimetry (DSC) and Fourier-Transform infrared spectroscopy (FT-IR) were performed. The results showed that all formulations exhibited higher percentage of drug dissolved in water (pH 6.4–6.6) compared to that at acidic medium (pH 1.2). Liquisolid compacts containing Synperonic® PE/L 81 demonstrated higher release rate at the different pH values. Formulations with PEG 400 displayed lower drug release rate, compared to conventional and liquisolid tablets. DSC and FT-IR indicated a possible interaction between furosemide and tablet excipients that could explain the dissolution results. Caprol® PGE-860, as a liquid vehicle, failed to produce furosemide liquisolid compacts.

Highlights

The solubility of active ingredient(s) is a matter of concern to formulators
The higher solubility of the drug in Caprol® PGE 860 compared with other liquid vehicles may be due to the longer non-polar chain of Caprol® PGE 860
Liquisolid tablets containing Synperonic® PE/L 81 as a new liquid vehicle exhibited greater dissolution due to the physical properties of this liquid vehicle which led to increased wetting properties and solubility of the drug; demonstrating higher drug release than those of conventionally made tablets

Summary

Introduction

The solubility of active ingredient(s) is a matter of concern to formulators. The poor dissolution rates of poorly water soluble drugs is still a substantial problem confronting drug development, such as hindering the development of parenteral products and limiting the bioavailability of oral products [1]. Soluble drugs that are administered orally will generally exhibit slow dissolution rates and incomplete bioavailability due to poor wettability of those drugs. This indicates that drugs are not sufficiently wetted before reaching absorption site [2]. As large proportions of new drug candidates have poor aqueous solubility, various formulation strategies were reported to overcome such a problem. Among these techniques is complexation with cyclodextrins, solid dispersion, co-precipitation and recently, the technique of ‘liquisolid compacts’. Since drug dissolution is often the rate limiting step in gastrointestinal absorption, the significant increase in wetting properties and surface area of drug particles available for dissolution from liquisolid compacts may be expected to display enhanced drug release characteristics and, improved oral bioavailability

Objectives

Results

Conclusion