A comparison of selected physico-chemical properties of calcium alginate fibers produced using two different types of sodium alginate.

Sodium alginate is a non-toxic natural polysaccharide found in marine brown algae. It is able to form solid gels by the action of poly-valent cations (commonly calcium but not magnesium) which cross-link the polysaccharide chains at the guluronic acid groups. Alginate-based products are popular in many industries, including food production and in pharmaceutical and biomedical applications. It is utilized in manufacture of wound-care products due to its biocompatibility and gel forming capabilities upon the absorption of wound exudate. Considering the potential influence of the alginate composition on the properties of the resultant fibers, two sodium alginate powders were selected based on their contrasting compositions. The GHB alginate was high in guluronic acid whereas the LKX alginate was high in mannuronic acid. The sodium alginate solutions (4% w/w) were extruded into a calcium chloride (3% w/v) bath to produce calcium alginate fibers. The fibers were dried at 22 °C and 32% relative humidity for 72 h. Selected properties of the blank (unloaded) fibers were analysed: diameter measurements by optical microscopy, mechanical strength using a universal testing machine, morphology by scanning electron microscopy, and calcium content by inductively coupled plasma atomic emission spectroscopy. One of the key aims of this work was to evaluate the variability of these properties along moderately large lengths of fiber and to determine the difference (if any) between replicate lengths of fibers. This study showed that the alginate type influenced selected properties of the resultant fibers. The mean diameter and calcium content of the GHB fibers were 232 µm and 2.79µmoles/mg respectively, whereas the LKX fibers were about 10% thicker and had 2.58µmoles/mg calcium ion content. The fibers of each alginate could be distinguished visually based on gross differences as well as differences in their microstructure. Mechanical testing of the fibers produced stress-strain plots displaying largely non-elastic behaviour. There was no statistically significant (p < 0.05) difference between the Young's modulus or the strain at break for the two types of fibers, namely about 5-5.6 GPa and 0.123-0.131 respectively. All the measured properties were found to be consistent along the nine sampling positions along the lengths of fibers and were reproducible between the different batches of fibers.

Swelling and diffusion studies of calcium polysaccharide gels intended for film coating.

The aim of this paper was to study the swelling and diffusion behaviors of calcium polysaccharide gel (CaPG) films prepared by an interfacial complexation technique, a new gel formation method that allowed calcium ions to diffuse from a source to form gel films with polysaccharide (i.e., alginate or pectin). The dynamic swelling behavior of CaPG films showed that swelling was a function of time. Most CaPG films showed a maximum amount of water absorption during the first few hours. The films swelled less in water and acidic media but extensively swelled in 0.1M NaCl. The rehydration of the dry films in the acidic media or the 0.1M NaCl solution also lead to the extraction of most of the calcium ions from the CaPG within 4h or less. Partitioning and diffusion of a model drug, theophylline (TPL), were measured through CaPG films equilibrated in different media. The partition and diffusion coefficients of TPL through CaPG films were found to vary, depending upon polysaccharide type, concentration and equilibration medium. The results suggest that both partition and pore mechanisms operated concurrently in the transport of TPL through CaPG films equilibrated in different media.

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: 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.

Development of polysaccharide gel-coated pellets for oral administration. 2. Calcium alginate.

Calcium alginate gel-coated pellets were developed by forming an insoluble gel coat on extruded-spheronized pellets by interfacial complexation. Experiments were designed to investigate the effect of pellet size, alginate type, alginate concentration, and dissolution medium on swelling and drug release behavior. Low swelling in acidic media was related to proton-calcium ion exchange forming insoluble acid gels. In contrast, partial formation of soluble sodium alginate in 0.1M NaCl induced water uptake, resulting in greater swelling. Drug release from coated pellets showed a lag time when the gel coat hydrated and swelled, followed by a zero-order release. Significantly slower release was observed when either the pellet size or the alginate concentration was increased. Alginate with high guluronic acid content gave the slowest release. Different types of alginate with high mannuronic acid content showed different release behaviors that are probably due to the different monomer sequences and botanical sources. The faster drug release in acidic media and 0.1M NaCl compared to water is probably due to reduced calcium cross-linking in the gel. These results suggest that the pellet size, alginate type and concentration and dissolution medium influenced the swelling and drug release behavior of calcium alginate gel-coated pellets.

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.

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.

In vitro analysis of the effect of in-line 1.2 micron filters on two formulations of propofol (2,6-diisopropyl phenol).

Recent evidence has shown improved outcomes in pediatric intensive care units with the intensive use of intravenous in-line filtration. This has caused resurgence in interest in filter use but has raised questions in relation to emulsion-based formulations such as propofol. Our objective was to test two propofol products, Diprivan(®) and Fresofol(®), with the Pall Lipipor(®) TNA and Lipipor NLF intravenous in-line filters and to assay the content before and after filtration under typical infusion conditions. The propofol emulsions were delivered from a 50 mL syringe through an extension set and into either a Lipipor TNA (50 mL/h(-1)) or Lipipor NLF (20 mL/h(-1)) filter. Samples were taken at regular intervals and assayed using a high-performance liquid chromatography method before and after filtration. No evidence was found of a significant concentration change during passage of either product through either model of filter. Propofol from two products was found to pass through two different types of Pall 1.2 µm intravenous in-line filters. There was no significant change in concentration before and after filtration under typical conditions of administration. In conclusion, administration of these products through these models of in-line filter would be safe and effective.

Comparison of selected physico-chemical properties of calcium alginate films prepared by two different methods.

Sodium alginate (SA) is a naturally occurring, non-toxic, polysaccharide that is able to form gels after exposure to calcium. These gels have been used in food and biomedical industries. This is the first direct comparison of two different methods of calcium alginate film production, namely interfacial gelation (IFG) and dry cast gelation (DCG). IFG films were significantly thicker than DCG films, and were more extensively rehydrated in water and 0.1M HCl than the DCG films. During rehydration in 0.1M HCl almost all calcium ions were lost. Under scanning electron microscopy, IFG films appeared less dense than DCG films. IFG films were mechanically weaker than DCG films, and both types of film were weaker after rehydration in 0.1M HCl compared with deionized water. Permeation of theophylline (TPL) was evaluated in-vitro; the diffusion coefficient (D) of the TPL was almost 90 times lower in DCG films than IFG films when both were rehydrated in water. Although the 0.1M HCl rendered both gels more permeable to TPL, D of TPL was still about five times lower in DCG compared to IFG films. The evaluation of selected physico-chemical properties of films is important, since this information may inform the choice of gelation technique used to produce calcium alginate coatings on pharmaceutical products.

Computer-based real-time analysis in mobile ocular screening.

Mobile ocular telemedicine is potentially an effective method to provide service in medically underserved areas and to screen large populations for abnormalities. Currently, digital images are acquired, stored, and transferred to readers for evaluation, after which the results are provided to the subjects. The transfer of large image files and the timeliness of the subsequent reading of images are significant factors for practical implementation of effective telemedicine screening. This work examines the feasibility of in situ real-time computer analysis of digital images to determine and classify the image results as normal and abnormal. This retrospective study used a photoscreening database of 360 patients ranging in ages from 6 months to 18 years. Computer analysis automatically classified the binocular photorefraction (PR) images, and these PR results were compared to those of the subjective clinical eye examinations provided. With an average processing time of approximately 15 seconds per examinee, the analysis found that the PR results can be categorized as: a positive group that requires referral (186 cases) with a predictive value of 98.9% (2 false-positives); a negative group (144 cases) with a predictive value of 89.6% (15 false-negatives); and an uncertain group (30 cases or 8.3%) that required resolution by readers. The real-time analysis code reduces by approximately 92% the manpower for image grading and electronic transmission at this stage of ocular evaluation. These results indicate the feasibility of this approach.