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. Polyoxyethylene-
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.