Abstract

The formulation of hydrophobic drugs into appropriate dosage forms is challenging due
to the problems associated with those drugs such as low solubility and poor dissolution.
Using a liquisolid system is a promising method to improve the dissolution of hydrophobic
drugs and in sustaining the release of hydrophilic drugs, in which solid drugs are
dispersed in non-volatile liquid vehicles. The aim of this research was to use the liquisolid
technique to enhance the dissolution rate of glibenclamide, a model hydrophobic drug,
and to sustain the release of metformin-HCl, as a model hydrophilic drug. The wet
granulation process was applied to liquisolid powders with the aim of overcoming issues
of poor powder flowability and compressibility, especially using high viscosity liquid
vehicles. This process was performed with liquisolid powders prior to compaction into
tablets. Different liquisolid formulations were prepared using three liquid vehicles
(polyethylene glycol400 (PEG® 400), Synperonic® PE/L44 and Cremophor® ELP), at 10
and 30 % w/w drug concentrations for glibenclamide; and 30% and 60% w/w drug
concentrations for metformin-HCl. Avicel®PH102 was used as a carrier, whilst colloidal
silicon dioxide was employed as a coating material to convert the wet mixtures into dry
powders. Potato starch, 5% w/w, as a disintegrant was blended with the mixtures
manually for 10 minutes and then 0.75% of magnesium stearate as a lubricant was added
and mixed for 5 minutes. The final powder (depending on its flowability and
compactability) was then compacted automatically using a single-punch tableting
machine to give tablets with 4 mg for glibenclamide and 40 mg for metformin-HCl.
Prepared liquisolid compacts were characterized by using British Pharmacopeia quality
control tests: uniformity of weight, friability, disintegration, hardness and drug dissolution.
iii
It was found, for both drugs, that by application of wet granulation to liquisolid powder
admixtures, the large-scale production of liquisolid compacts is feasible, which can be
easily adapted to the pharmaceutical industry. In addition to enhancing the flowability and
compressibility of the powders, the glibenclamide dissolution was also improved due to
the enhanced binding of particles and because of the wetting effect of liquid vehicles on
the hydrophobic drug, which make the drug more available for dissolution.
For the sustained release preparations of liquisolid metformin-HCl, hydroxyl propyl
cellulose (HPC) was used as a novel carrier in liquisolid compacts. The results showed
92% drug release after 12 hours using Cremophor®ELP (with 30% w/w drug
concentration) which was the best sustained drug release formulation. Additionally,
Eudragit® RL30D and Eudragit® RLPO have been used to study their effects on drug
release from liquisolid formulations, examining if they can sustain or give more rapid drug
release. Both types of Eudragit revealed immediate release with metformin-HCl rather
than sustained drug release, with the tablets disintegrating within seconds. This suggests
formulating orodispersible metformin-HCl tablets using Eudragit® RL30D as a liquid
vehicle.
In summary, liquisolid technology has led to promising results, not only in enhancing the
drug dissolution of hydrophobic drugs, but also in sustaining and promoting the release
of hydrophilic drugs.