Satit Puttipipatkhachorn

Physical properties and molecular behavior of chitosan films.

Chitosan films, varying in molecular weight and degree of deacetylation, were prepared by a casting technique using acetic acid as a dissolving vehicle. The physicochemical properties of the films were characterized. Both molecular weight and degree of deacetylation affected the film properties. Powder X-ray diffraction patterns and differential scanning calorimetry thermograms of all chitosan films indicated their amorphous state to partially crystalline state with thermal degradation temperature lower than 280–300°C. The increase in molecular weight of chitosan would increase the tensile strength and elongation as well as moisture absorption of the films, whereas the increase in degree of deacetylation of chitosan would either increase or decrease the tensile strength of the films depending on its molecular weight. Moreover, the higher the degree of deacetylation of chitosan the more brittle and the less moisture absorption the films became. All chitosan films were soluble in HCl–KCl buffer (pH 1.2), normal saline, and distilled water. They swelled in phosphate buffer (pH 7.4), and cross-linking between chitosan and phosphate anions might occur. Finally, transmission infrared and 13C-NMR spectra supported that chitosan films prepared by using acetic acid as a dissolving were chitosonium acetate films.

Drug physical state and drug–polymer interaction on drug release from chitosan matrix films

Four different grades of chitosan varying in molecular weight and degree of deacetylation were used to prepare chitosan films. Salicylic acid and theophylline were incorporated into cast chitosan films as model acidic and basic drugs, respectively. Crystalline characteristics, thermal behavior, drug-polymer interaction and drug release behaviors of the films were studied. The results of Fourier transform infrared and solid-state 13C NMR spectroscopy demonstrated the drug-polymer interaction between salicylic acid and chitosan, resulting in salicylate formation, whereas no drug-polymer interaction was observed in theophylline-loaded chitosan films. Most chitosan films loaded with either salicylic acid or theophylline exhibited a fast release pattern, whereas the high viscosity chitosan films incorporated with salicylic acid showed sustained release patterns in distilled water. The sustained release action of salicylic acid from the high viscosity chitosan films was due to the drug-polymer interaction. The mechanism of release was Fickian diffusion control with subsequent zero order release. It was suggested that the swelling property, dissolution characteristics of the polymer films, pK(a) of drugs and especially drug-polymer interaction were important factors governing drug release patterns from chitosan films.

Characterization and mosquito repellent activity of citronella oil nanoemulsion

Encapsulated citronella oil nanoemulsion prepared by high pressure homogenization at varying amounts of surfactant and glycerol, was studied in terms of the droplet size, stability, release characteristics and in vivo mosquito protection. Transparent nanoemulsion can be obtained at optimal concentration of 2.5% surfactant and 100% glycerol. Physical appearance and the stability of the emulsion were greatly improved through an addition of glycerol, owing to its co-solvent and highly viscous property. The increasing emulsion droplet increased the oil retention. The release behavior could be attributed to the effect of droplet size and concentrations of surfactant and glycerol. By fitting to Higuchis equation, an increase in glycerol and surfactant concentrations resulted in slow release of the oil. The release rate related well to the protection time where a decrease in release rate can prolong mosquito protection time.

Improved dissolution of ofloxacin via solid dispersion

Abstract The objective of this study was to improve the dissolution rate of a sparingly water soluble drug, ofloxacin, by solid dispersion systems with urea and mannitol. Differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD) analysis and infrared spectroscopy (IR) were performed to evaluate the physicochemical properties of the prepared solid dispersions. The dissolution rate of ofloxacin was markedly increased in solid dispersion of urea and mannitol. Solubility studies revealed a marked increase in the solubility of ofloxacin with an increase in urea concentration. Mannitol concentration had no effect on the solubility of ofloxacin. The PXRD study revealed that the crystallinity of ofloxacin was decreased as the ratio of drug to carrier was decreased. The results from DSC and IR indicated that there was no interaction between drug and carriers.

Dissolution improvement of high drug-loaded solid dispersion.

This study focused on an investigation of a high drug-loaded solid dispersion system consisting of drug, carrier, and surfactant. Solid dispersions of a water-insoluble ofloxacin (OFX) with polyethylene glycol (PEG) of different molecular weights, namely binary solid dispersion systems, were prepared at drug to carrier not less than 5∶5. Polysorbate 80, a nonionic surfactant, was incorporated into the binary solid dispersion systems as the third component to obtain the ternary solid dispersion systems. The powder x-ray diffraction and differential scanning calorimetric studies indicated that crystalline OFX existed in the solid dispersions with high drug loading. However, a decreased crystallinity of the solid dispersions obtained revealed that a portion of OFX was in an amorphous state. The results indicated a remarkably improved dissolution of drug from the ternary solid dispersion systems when compared with the binary solid dispersion systems. This was because of polysorbate 80, which improved wettability and solubilized the non-molecularly dispersed or crystalline fraction of OFX.

Morphology and buoyancy of oil-entrapped calcium pectinate gel beads

A new emulsion-gelation method to prepare oil-entrapped calcium pectinate gel (CaPG) beads capable of floating in the gastric condition was designed and tested. The gel beads containing edible oil were prepared by either being gently mixed or homogenized an oil phase and a water phase containing pectin, and then extruded into calcium chloride solution with gentle agitation at room temperature. The gel beads formed were then separated, washed with distilled water, and dried at 37°C for 12 hours. A model of the emulsion-gelation process to illustrate the formation of oil-entrapped CaPG beads was proposed. The effect of selected factors, such as type of oil, percentage of oil, and type of pectin on morphology and floating properties was investigated. The oil-entrapped calcium pectinate gel beads floated if a sufficient amount of oil was used. Scanning electron photomicrographs demonstrated very small pores, ranging between 5 and 40 μm, dispersed all over the beads. The type and percentage of oil play an important role in controlling the floating of oil-entrapped CaPG beads. The results suggested that oil-entrapped CaPG beads were promising as a carrier for intragastric floating drug delivery.

Effect of degree of esterification of pectin and calcium amount on drug release from pectin-based matrix tablets.

The aim of this work was to assess the effect of 2 formulation variables, the pectin type (with different degrees of esterification [DEs]) and the amount of calcium, on drug release from pectin-based matrix tablets. Pectin matrix tablets were prepared by blending indomethacin (a model drug), pectin powder, and various amounts of calcium acetate and then tableting by automatic hydraulic press machine. Differential scanning calorimetry, powder x-ray diffraction, and Fourier transformed-infrared spectroscopy studies of the compressed tablets revealed no drug-polymer interaction and the existence of drug with low crystallinity. The in-vitro release studies in phosphate buffer (United States Pharmacopeia) and tris buffer indicated that the lower the DE, the greater the time for 50% of drug release (T50). This finding is probably because of the increased binding capacity of pectin to calcium. However, when the calcium was excluded, the pectins with different DEs showed similar release pattern with insignificant difference of T50. When the amount of calcium acetate was increased from 0 to 12 mg/tablet, the drug release was significantly slower. However, a large amount of added calcium (ie, 24 mg/tablet) produced greater drug release because of the partial disintegration of tablets. The results were more pronounced in phosphate buffer, where the phosphate ions induced the precipitation of calcium phosphate. In conclusion, both pectin type and added calcium affect the drug release from the pectin-based matrix tablets.

Development of sustained release theophylline pellets coated with calcium pectinate

Abstract We have produced cores containing theophylline, calcium acetate and microcrystalline cellulose by extrusion-spheronization and then applied a coating of calcium pectinate by interfacial complexation. After drying, the coatings were observed by scanning electron microspcopy to be 50–80 μm thick. The type of pectin used, the core size and the coating time all influenced the yield of theophylline in the coated cores. Theophylline release from the uncoated cores was rapid and linear with the square root of time. The in-vitro release of theophylline from the coated cores was tested in water, simulated gastric fluid USP minus pepsin (SGF) and a Tris buffer (pH 7.4). In general, release was essentially constant until 75–80% of the drug was released. The large coated cores released over a period of about 4 h and the small coated cores released over a period of 2 h. Although the coatings swelled more when they were rehydrated in the Tris buffer compared to water and SGF, theophylline release was similar in all the dissolution media. In particular, release was not increased by SGF as may have been expected from studies using a similar polysaccharide sodium alginate. Calcium pectinate coatings are easy to apply, do not require harsh conditions and may yield release profiles which are relatively independent of pH.

Water-soluble β-cyclodextrin grafted with chitosan and its inclusion complex as a mucoadhesive eugenol carrier

Inclusion complex between water-soluble βCD-grafted chitosan derivatives (QCD-g-CS) and eugenol (EG) was investigated as a new type of mucoadhesive drug carrier. The QCD-g-CSs were synthesized with various βCD moieties ranging from 5 to 23%. Spontaneous inclusion complex of these derivatives and EG were found and confirmed by FTIR and simulation study. Self-aggregated formations of QCD-g-CS were found, according to fluorescence and TEM studies, where the formations were preferable for QCD11g-CS and QCD5-g-CS. EG can be included in both βCD hydrophobic cavity and hydrophobic core of QCD-g-CS self-aggregates, resulting in varying entrapment efficiencies. Degree of QCD substitution on QCD-g-CS plays an important role on their physical properties, due to steric hindrance. The QCD11-g-CS showed excellent mucoadhesion, compared to the QCD5-g-CS and QCD23-g-CS. Moreover, the inclusion complex between QCD-g-CS and EG tend to express higher antimicrobial activities against Candida albicans, Streptococcus oralis and Streptococcus mutans, than the native QCD-g-CS.

Calcium pectinate gel coated pellets as an alternative carrier to calcium pectinate beads

A conventional method of using drug entrapped in calcium pectinate beads as sustained release drug delivery systems have long been suffering from too rapid an in-vitro release. An approach to solve this setback by the method of calcium pectinate gel (CPG) coated pellets was then initiated. The spherical theophylline pellets, which contain calcium acetate, were prepared using an extrusion-spheronization method and then coated with pectin solution, using an interfacial complexation process. An insoluble and uniform coating of CPG was formed around the pellets. The comparison was made between theophylline uncoated pellets, calcium pectinate beads and this developed method by the variation of coating time and the type of pectin. The results in simulated gastric fluid (SGF) and water showed that theophylline release from the coated pellets was slower than that from the beads. The time for 50% release of theophylline (t50) from the CPG coated pellets in water and SGF are greater than the uncoated cores and the conventional beads. These results suggested that the coated pellets system were able to retard the release of theophylline to a greater extent than the conventional method. Therefore, this approach has been successfully achieved.