Development of polysaccharide gel-coated pellets for oral administration: swelling and release behavior of calcium pectinate gel.

The aim of this study was to examine the effect of pellet size, pectin type, pectin concentration, and dissolution medium on the swelling and drug release behavior of spherical pellets containing theophylline and coated with 2 different calcium pectinates, using a multi-level factorial design approach. The spherical pellets were prepared by an extrusion-spheronization method and then coated with calcium pectinate using the diffusion-controlled interfacial complexation technique, which provides a defect-free and uniform coating on solid cores. Theophylline release from the pellets was slowed by the application of the coatings. The time to release 50% of the payload (ie, T50) in an acidic medium was approximately 7 minutes from uncoated small pellets and was 55 minutes after an amidated calcium pectinate coat was applied; a comparable coat on large pellets showed a T50 of 93 minutes. Drug release profiles of dry coated pellets showed a lag time (all less than 20 minutes) when the gel coat hydrated and swelled, followed by a zero-order release. It was found that the release rate was controlled by the pellet size, pectin type, pectin concentration, and dissolution medium.

Effect of drug solubility on release behavior of calcium polysaccharide gel-coated pellets.

The aim of this study was to investigate the effect of drug solubility on the release behavior from calcium polysaccharide gel (CaPG)-coated pellets. Three different drugs with similar chemical structure, but different water solubility, namely caffeine (CAF), theophylline (TPL) and theobromine (TBR), were used. Drug-loaded spherical pellets were manufactured by an extrusion-spheronization method. The CaPG was applied on the pellets loaded with different drugs by interfacial complexation coating. The encapsulation efficiency of coated pellets was found to vary from 57.6 to 84.3%, depending on the solubility of the active drug and polysaccharide type. Drug release from different uncoated pellets was relatively unaffected by pH and release media but depended mainly on drug solubility. Release behavior was significantly modified in the pellets coated with CaPG, for all of the drugs tested. Drug release from coated pellets of the different drugs showed different release kinetics. The difference in the drug release is probably due to the difference in the drug dissolution within the core, before its partition and diffusion through the CaPG coat. The CAF dissolved faster and achieved a higher concentration in solution, which drove diffusion. The release of TBR from the coated pellets was much slower than that of the CAF or TPL because of its low solubility. However, the release of all drugs was about four- to sixfold slower for coated than uncoated pellets, suggesting that the coating influenced the retardation of drug release from the coated pellets. Therefore, the CaPG coating may provide a sustained release delivery system for all drugs tested.

Effect of selected non-ionic surfactants on the flow behavior of aqueous veegum suspensions.

The aim of this work was to investigate the influence of some non-ionic surfactants, Tween 80 and Brij 98, on the viscosity and flow behavior of a commercial montmorillonite clay, Veegum Granules. The effect of different concentrations of the surfactants on the shear stress-shear rate rheograms of hydrated concentrated clay suspensions was determined by shear viscometry. The addition of either surfactant increased the plastic viscosity and the yield stress of the suspensions. Furthermore, both surfactants altered the thixotropy of the suspensions to an extent that depended on both the surfactant concentration and the time of equilibration of the surfactant and Veegum. Brij 98 had a greater and more rapid effect. It is proposed that the surfactant polar head-groups anchor at the tetrahedral sheet surface, leaving the alkyl chains extending away from the edges and faces. Consequently, the alkyl chains undergo hydrophobic interactions that facilitate the association between the platelets and increase the physical structure within the suspension. Stereochemical differences between the polar groups may lead to differences in the way the surfactants associate with the tetrahedral sheet and hence their ultimate effect on the rheological behavior. There is a significant interaction between these surfactants and montmorillonite clays, and the rheological changes that occur could have a major impact on any pharmaceutical formulation that uses these ingredients.

Development of polysaccharide gel coated pellets for oral administration 1. Physico-mechanical properties.

Spherical pellets containing theophylline, calcium acetate and microcrystalline cellulose were extruded and spheronized, before being coated with six different pectins or alginates by interfacial complexation. The aim of this study was to discover the effect of the coatings on physico-mechanical properties that will be crucial in determining the pellets' utility as sustained release systems. An insoluble, smooth and uniformly thick coat of calcium polysaccharide was formed around the core pellets. A factorial experiment was designed to investigate the effect of pellet size and polysaccharide type and concentration on the entrapment efficiency, mechanical properties and other physical characteristics. Coated pellets were observed by scanning electron microscopy and, depending on the particular polysaccharide used, the dry coats were found to be 30-80 microm thick. The size of pellet, the type and concentration of polysaccharide influenced the yield of theophylline in the coated pellets. Although the mechanical properties of the pellets were improved by applying any of the gel coats, use of an alginate with a high content of guluronic acid or an amidated pectin coating gave the best results. This is probably because both of these have significant potential to form very stable cross-links within the gel coats.

A novel gel formation method, microstructure and mechanical properties of calcium polysaccharide gel films.

Hydrophilic gels, formed by the interaction of calcium ions with either sodium alginate or potassium pectinate, can be deposited as a wet coating on to the surface of drug loaded pellets. If the coated pellets are dried, they could be dispensed to a patient in a capsule for oral delivery of the active drug. In contact with the aqueous fluids of the gastrointestinal tract, the gel coat will rehydrate, swell and will sustain the release of active drug from the core. In order to facilitate the development and refinement of this novel coated system, it is beneficial to have a method that can produce free gel films in a manner that closely mimics the way the gel coat is formed and deposited on the pellet surface. Traditional film producing methods would involve the spraying or depositing (by evaporation) the gel forming polysaccharide on to an inert surface, drying it and then exposing the dry film to a solution containing calcium ions. Because the film is dry before it is gelled, it is fundamentally different to the wet gel coats that are deposited on to the pellets. We have developed a method to produce wet gel films and have evaluated different manufacturing conditions in order to optimize the quality of the completed gel film. Additionally, we have used these films to assess the effect that the type of polysaccharide and the environmental conditions experienced during rehydration (pH and ionic strength) has on the mechanical properties and the microscopic morphology of the gel. Irrespective of the rehydration medium, the calcium pectinate gel films were softer, weaker and more porous, than the calcium alginate films. Although calcium alginate gels that were rehydrated in 0.1M NaCl were porous, the same films rehydrated in either water, simulated gastric fluid USP (without pepsin) or 0.1M HCl were stronger and much more dense microscopically. Furthermore, of the four different alginates that were evaluated, those with a high content of guluronic acid saccharides were the strongest but most brittle when rehydrated in water.