Calcium pectinate gel beads for controlled release drug delivery:: I. Preparation and in vitro release studies

Calcium pectinate gel (CPG) beads of indomethacin, a poorly soluble drug, were prepared by dispersing indomethacin in a solution of pectin and then dropping the dispersion into calcium chloride solution. The droplets instantaneously formed gelled spheres by ionotropic gelation. The effect of several factors such as pectin type, the presence of a hardening agent and the drug loading were investigated on the percentage of drug entrapped, size distribution and drug release from the CPG beads. The release characteristics were studied using the rotating basket dissolution method. Strong spherical beads with narrow size distributions, high yields and good entrapment efficiencies could be prepared. All factors investigated have significantly affected the release of indomethacin from CPG beads. The mechanism of drug release from CPG beads followed the diffusion controlled model for an inert porous matrix. Therefore, calcium pectinate gel could be a useful carrier for controlled release drug delivery of poorly soluble drugs.     

Alginate-based pellets prepared by extrusion/spheronization: a preliminary study on the effect of additive in granulating liquid.

The aim of this study was to investigate the possibility of producing alginate-based pellets by extrusion/spheronization and also to improve the formation of spherical alginate-based pellets by investigating the effect of additive in granulating liquid on characteristics and drug release from resulting pellets. Two types of sodium alginate (30%) were evaluated in combination with theophylline (20%), microcrystalline cellulose (50%) and different granulation liquids. The pellets were then prepared in a basket extruder, then spheronized and dried. The final products were characterized by morphological examination and drug release study. Different additives in the granulating liquid influenced the ability of the extruded mass to form pellets (the processability) with this technique. However, different sodium alginate types responded to shape modifications to a different extent. Long, dumbbell-shaped pellets were obtained with viscous granulating liquids. However, short, nearly spherical pellets were obtained with watery granulation liquid with calcium chloride that reduced the swelling ability of sodium alginate. Improvements in the pellet characteristics were also dependent on the sodium alginate type employed. Most of pellet formulations released about 75-85% drug within 60min and showed a good fit into both Higuchi and Korsmeyer-Peppas equations. Higher amount of 3% calcium chloride, as a granulating liquid, in the formulation showed higher mean dissolution time resulting from the cross-linking properties of calcium ions to the negative charges of alginate molecules.     

Alginate-based pellets prepared by extrusion/spheronization: Effect of the amount and type of sodium alginate and calcium salts

Pellets containing microcrystalline cellulose (MCC), a model drug (theophylline) and a range of levels of sodium alginate (i.e., 10–50% w/w) were prepared by extrusion/spheronization. Two types of sodium alginate were evaluated with and without the addition of either calcium acetate or calcium carbonate (0, 0.3, 3 and 10% w/w). The effects of amount and type of sodium alginate and calcium salts on pellet properties, e.g., size, shape, morphology and drug release behavior, were investigated. Most pellet formulations resulted in pellets of a sufficient quality with respect to size, size distribution and shape. The results showed that the amounts of sodium alginate and calcium salts influenced the size and shape of the obtained pellets. However, different types of sodium alginate and calcium salt responded to modifications to a different extent. A cavity was observed in the pellet structure, as seen in the scanning electron micrographs, resulting from the forces involved in the spheronization process. Most of pellet formulations released about 75–85% drug within 60 min. Incorporation of calcium salts in the pellet formulations altered the drug release, depending on the solubility of the calcium salts used. The drug release data showed a good fit into both Higuchi and Korsmeyer–Peppas equations.     

Effect of alkali treatment on properties of native shellac and stability of hydrolyzed shellac

The objective of this study was to investigate the effect of alkali treatment on properties of shellac. The native shellac was treated with sodium hydroxide for 15, 30, and 60 min to obtain hydrolyzed shellac. All types of shellac, namely native and hydrolyzed shellac at various times of treatment, were then prepared in films as free acid and ammonium salt forms by using ethanol and ammonium hydroxide solution, respectively. The results showed that alkali treatment caused an increase in acid value and a decrease in ester value. This is due to higher free carboxylic and hydroxyl groups caused by ester bond breaking. The longer the alkali treatment the higher impact of bond breaking, therefore, causing an increase in acid value, solubility at pH 7, strain, a decrease in ester value, water vapor permeability coefficient, and stress. The films were then kept at 40 degrees C, 75% RH for a period of three months. The aging effect led to an esterification of free carboxylic and hydroxyl groups, resulting in the significant change of acid value, ester value, and insoluble solid for both native and hydrolyzed shellac films in acid form. On the other hand, all types of shellac films in ammonium salt form exhibited a reasonable stability in physicochemical and mechanical properties as all films were protected from the esterification due to the formation of ammonium salt at the carboxylic binding site. It could be concluded that alkali treatment could produce hydrolyzed shellac with higher solubility in the intestine, the stability was yet in dilemma unless the shellac was in an ammonium salt form. The result obtained could, thus, provide a guideline in the use of shellac.     

Central Nervous System Toxoplasmosis with an Increased Proportion of Circulating γδ T Cells in a Patient with Hyper-IgM Syndrome

Hyper-IgM syndrome represents a diverse group of immunodeficiencies characterized by normal or high serum IgM concentrations with decreased or absent IgG, IgA, and IgE. The X-linked form of hyper-IgM syndrome is caused by mutations in the CD40 ligand gene, preventing its expression on activated T cells. The CD40 ligand–CD40 interaction is critical for effective isotype switching and for initiating antigen-specific T cell responses. In addition to recurrent pyogenic infections, patients with the CD40L defect also have opportunistic infections. An increased proportion of circulating T cells, shown to be important early during primary infections, has been demonstrated in numerous infectious diseases including toxoplasmosis. Here, we report a patient with hyper-IgM syndrome and CNS toxoplasmosis, who showed a marked increase in T cells in his peripheral blood and who has responded well to treatment of his toxoplasmosis and to high-dose immunoglobulin replacement therapy.     

Swelling and erosion of pectin matrix tablets and their impact on drug release behavior.

The aim of this study was to investigate swelling and erosion behaviors of hydrophilic matrix tablets using pectin and their impact on drug release. The matrix tablets were prepared by direct compression using different types of pectin. Swelling and erosion studies of pectin matrix tablets were carried out in various media. The pectin matrix tablets formed a continuous gel layer while in contact with the aqueous medium undergoing a combination of swelling and erosion. The swelling action of pectin matrices was controlled by the rate of its hydration in the medium. Release studies showed that the swelling and erosion of matrices influenced the drug release. The extent of matrix swelling, erosion and diffusion of drug determined the kinetics as well as mechanism of drug release from pectin-based matrix tablets. The release data showed a good fit into the power law or the Korsmeyer-Peppas equation indicating the combined effect of diffusion and erosion mechanisms of drug release.     

Modulation of drug release kinetics of shellac-based matrix tablets by in-situ polymerization through annealing process.

A new oral-controlled release matrix tablet based on shellac polymer was designed and developed, using metronidazole (MZ) as a model drug. The shellac-based matrix tablets were prepared by wet granulation using different amounts of shellac and lactose. The effect of annealing temperature and pH of medium on drug release from matrix tablets was investigated. The increased amount of shellac and increased annealing temperature significantly affected the physical properties (i.e., tablet hardness and tablet disintegration) and MZ release from the matrix tablets. The in-situ polymerization played a major role on the changes in shellac properties during annealing process. Though the shellac did not dissolve in acid medium, the MZ release in 0.1N HCl was faster than in pH 7.3 buffer, resulting from a higher solubility of MZ in acid medium. The modulation of MZ release kinetics from shellac-based matrix tablets could be accomplished by varying the amount of shellac or annealing temperature. The release kinetics was shifted from relaxation-controlled release to diffusion-controlled release when the amount of shellac or the annealing temperature was increased.