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Development of gellan gum fluid gel as modified release drug delivery systems

Mahdi, Mohammed Hamzah (2016) Development of gellan gum fluid gel as modified release drug delivery systems. Doctoral thesis, University of Huddersfield.

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Abstract

Gelation of polysaccharides under shear conditions results in the formation of a weak gel which is able to resist elastic mechanical deformation at small strains but will flow if subjected to higher strains. The resulting material, described in the literature as a fluid gel or a sheared gel, consists of gelled microparticles which can be formulated to collectively act in bulk, as pourable viscoelastic fluids whilst retaining true gel characteristics at the micro/nano level. The tuneable behaviour of these fluid gel systems makes them potentially useful in pharmaceutical applications. Fluid gels prepared from gellan gum are particularly attractive, due to its sensitivity to physiological fluids, unique rheological and physical properties, and current regulatory approval for use as a food additive and pharmaceutical excipient. Therefore, the aim of the present study was to investigate gellan gum fluid gels as a new modified release drug delivery platform. The formation and production of fluid gels using low acyl (LA) gellan, high acyl (HA) gellan and LA HA gellan blends was investigated and applied in three different dosage forms; a modified release oral liquid, a mucoadhesive nasal spray and a topical formulation.
A modified release oral liquid was designed using a fluid gel prepared from LA gellan gum. It was demonstrated that 0.75 % w/w LA gellan gum fluid gel, containing ibuprofen as the drug, could be formulated to have a similar viscosity profile as a marketed oral ibuprofen liquid. Furthermore, due to the acid insolubility of gels prepared from LA gellan, no ibuprofen was released in stimulated gastric fluid. Subsequent release at pH 7.4 however, was affected by the duration of exposure and strength of the acidic pH used and a linear relationship between onset of release and the preceding duration of acid exposure was observed. Delayed release was a result of increasing gel stiffness, a consequence of the acidity of the initial release media and exposure time. A much faster release rate was measured when exposure time in acid was 10 min compared with 60 min. This study highlights the potential to design fluid gels that are tuned to have a specified stiffness at a particular pH and exposure time allowing the intelligent design oral liquids with specific modified release behaviour.
The second part of this study was to prepare mucoadhesive nasal drug delivery systems to enhance the retention of the nasal spray dosage form in the nasal cavity. Several groups have investigated using LA gellan solution as a drug delivery vehicle but only limited research however, has been performed on HA gellan for this purpose, despite its properties being more conducive to mucoadhesion. HA gellan (even with low concentration 0.25 % w/w) produces highly elastic gels below 60 °C which make it difficult to spray using a mechanical spray device. To address this problem, fluid gels were prepared as these systems can behave as sprayable viscoelastic fluids. In this study the rheological behaviour was investigated and the mucoadhesion behaviour of fluid gels prepared from the two different types of gellan (HA and LA) and fluid gels prepared from a blend of LA HA gellan. The results demonstrated that by preparing fluid gels from a blend of LA HA gellan, the rheological properties were sufficient to spray through a standard nasal spray device. Moreover, the fluid gels significantly enhanced both HA and LA gellan mucoadhesion properties.
In the final part of this thesis the topical application of gellan fluid gels was explored. A range of gellan fluid gel formulations were prepared containing diclofenac sodium for topical application. The rheological results showed that it was possible to produce a topical formulation with a viscosity and the mechanical strength similar to that of the commercially available Voltaren® gel using 1 % w/w of a 50:50 LA HA gellan blend. The permeation results highlighted that the penetration of diclofenac through procaine tissue is significantly increased by increasing gellan concentration and decreasing sodium ion concentration in the formulation.

Item Type: Thesis (Doctoral)
Subjects: R Medicine > R Medicine (General)
R Medicine > RM Therapeutics. Pharmacology
Schools: School of Applied Sciences
Depositing User: Sharon Beastall
Date Deposited: 22 Nov 2016 13:16
Last Modified: 01 Dec 2016 19:33
URI: http://eprints.hud.ac.uk/id/eprint/30293

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