Wiwat Pichayakorn

Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin, and absorption studies in rats

This study describes the development and characterization of self-microemulsifying drug delivery systems (SMEDDS) in liquid and pellet forms that result in improved solubility, dissolution, and in vivo oral absorption of the poorly water-soluble compound curcumin. Solubility of curcumin was determined in various vehicles, including oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were constructed to identify the most efficient self-emulsification region. The optimized SMEDDS used for curcumin formulations in liquid and pellet forms contained 70% mixtures of two surfactants: Cremophor EL and Labrasol (1:1), and 30% mixtures of oil: Labrafac PG and Capryol 90 (1:1). The curcumin-SMEDDS in liquid and pellet formulations rapidly formed fine oil-in-water microemulsions, with particle size ranges of 25.8-28.8 nm and 29.6-32.8 nm, respectively. The in vitro rate and extent of release of curcumin from liquid SMEDDS and SMEDDS pellets was about 16-fold higher than that of unformulated curcumin. Plasma concentration-time profiles from pharmacokinetic studies in rats dosed with liquid and pelleted SMEDDS showed 14- and 10-fold increased absorption of curcumin, respectively, compared to the aqueous suspensions of curcumin. Curcumin-SMEDDS liquid and curcumin-SMEDDS pellets were found to be stable up to 6 months under intermediate and accelerated conditions. These studies demonstrate that the new self-microemulsifying systems in liquid and pellet forms are promising strategies for the formulation of poorly soluble lipophilic compounds with low oral bioavailability.

Evaluation of cross-linked chitosan microparticles containing metronidazole for periodontitis treatment.

The aims of this study were to find the optimal formulation for the preparation of metronidazole-loaded chitosan microparticles (MTZ-MPs) via an emulsion cross-linking process, and to compare the in vitro release of MTZ from hydrogels and films containing the drug in forms of MTZ-MPs and raw powders. The effects of emulsifier type and concentration, amount of cross-linking agent, cross-linking time, drug:chitosan ratio, form of drug adding and washing method on the properties of the MTZ-MPs were investigated. The results indicated that the optimal conditions for round and free-flowing MTZ-MPs with a high percentage of entrapped drug and preferable release profile were 1% of Span80 in soybean oil, 5% of glutaraldehyde based on chitosan solution, 30 min of cross-linking time, 1:1 drug:chitosan ratio, drug adding in form of ethanol solution and washing with hexane only. MTZ-MPs prepared from the optimal formulation were incorporated in mucoadhesive hydrogel and film. The release profiles of the drug from hydrogel and film containing MTZ-MPs were in prolong pattern compared with those containing drug powders. However, the hydrogels exhibited higher preferable pattern of release profile than the films. Therefore, the hydrogel containing MTZ-MPs was possible to be further clinically investigated for peridontitis treatment.

Gentamicin sulfate-loaded porous natural rubber films for wound dressing.

Antimicrobial wound dressings have been developed for effectiveness of wound therapy. In this study, gentamicin sulfate was loaded into modified porous natural rubber films. The hydrophilic porous structure in natural rubber films was formed when the polar liquid such as glycerin or triethyl citrate and hydrophilic xanthan gum were blended. Film properties including morphology, drug release, water sorption and erosion, mechanical property, adhesive property, surface free energy, water vapor transmission rate, oxygen permeation, and antimicrobial activity were determined. The angiogenesis activity of films was investigated using chick chorio-allantoic membrane assay. For the system containing triethyl citrate, bi-layers comprising of a dense-top layer and a high porous-bottom layer were observed. Xanthan gum enhanced the water sorption capacity and modified to obtain the optimum rate of the drug release from the film. The developed film topography with dense-top layer induced the low adhesive property, water vapor and oxygen permeability whereas demonstrated good antimicrobial activities against Staphylococcus aureus and Pseudomonas aeruginosa with angiogenic activity. Therefore it had the potential use for medicated wound dressing.

Deproteinized natural rubber film forming polymeric solutions for nicotine transdermal delivery

Film forming polymeric solutions were prepared from DNRL blended with MC, PVA, or SAG, together with dibutylphthalate or glycerine used as plasticizers. These formulations were easily prepared by simple mixing. In a preliminary step, in situ films were prepared by solvent evaporation in a Petri-dish. Their mechanical and physicochemical properties were determined. The in vitro release and skin permeation of nicotine dissolved in these blended polymers were investigated by a modified Franz diffusion cell. The formulations had a white milky appearance, and were homogeneous and smooth in texture. Their pH was suitable for usage in skin contact. The mechanical property of in situ films depended on the ingredients but all compatible films were in an amorphous phase. The DNRL/PVA was shown to be the most suitable mixture to form completed films. The in vitro release and skin permeation studies demonstrated a biphasic release that provided an initial rapid release followed by a constant release rate that fitted the Higuchi’s model. Nicotine loaded DNRL/PVA series were selected for the stability test for 3 months. These formulations needed to be kept at 4°C in tight fitting containers. In conclusion, film forming polymeric solutions could be developed for transdermal nicotine delivery systems.

Effect of Eriochrome Black T on the gelatinization of xyloglucan investigated using rheological measurement and release behavior of Eriochrome Black T from xyloglucan gel matrices

A novel gel system was obtained by mixing aqueous solutions of tamarind seed xyloglucan (TSX) and Eriochrome Black T (EBT), an antiangiogenic compound. The shear-viscosity flow curves revealed that all the studies mixtures displayed a shear thinning behavior. Viscosity increased with increasing EBT concentrations. According to frequency sweep tests, mixtures at EBT concentration of 1.30% and 2.50% (w/v) in 1% (w/v) TSX formed a weak gel. The time sweep tests revealed that these mixtures remained as sol at room temperature (25 degrees C) for a long period of time but turned into gel in a short time at body temperature (37 degrees C). The in vitro EBT release profiles demonstrated sustained release of EBT. Loading concentration of EBT affected the gel strength and consequently the release mechanism of EBT. According to release kinetic analyses, the release profiles of 1.30% and 2.50% (w/v) EBT systems occur through an anomalous mechanism and Fickian diffusion, respectively. In conclusion, these EBT-TSX systems appear to be suitable as injectable implants for sustained delivery of EBT at a site of application, and as such they may be beneficial for the future treatment of solid malignant tumors.

Formulation, physicochemical characterization, and in vitro study of chitosan/HPMC blends-based herbal blended patches.

The current work prepared chitosan/hydroxypropyl methylcellulose (HPMC) blends and studied the possibility of chitosan/HPMC blended patches for Zingiber cassumunar Roxb. The blended patches without/with crude Z. cassumunar oil were prepared by homogeneously mixing the 3.5% w/v of chitosan solution and 20% w/v of HPMC solution, and glycerine was used as plasticizer. Then, they were poured into Petri dish and produced the blended patches in hot air oven at 70 ± 2°C. The blended patches were tested and evaluated by the physicochemical properties: moisture uptake, swelling ratio, erosion, porosity, Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction, and photographed the surface and cross-section morphology under SEM technique. Herbal blended patches were studied by the in vitro release and skin permeation of active compound D. The blended patches could absorb the moisture and became hydrated patches that occurred during the swelling of blended patches. They were eroded and increased by the number of porous channels to pass through out for active compound D. In addition, the blended patches indicated the compatibility of the blended ingredients and homogeneous smooth and compact. The blended patches made from chitosan/HPMC blends provide a controlled release and skin permeation behavior of compound D. Thus, the blended patches could be suitably used for herbal medicine application.

Characterization of Antimicrobial Agent Loaded Eudragit RS Solvent Exchange-Induced In Situ Forming Gels for Periodontitis Treatment

Eudragit RS (ERS), a quaternary polyacrylate positively charged polymer, exhibits a very low permeability and swells in aqueous media independently of pH without dissolving. Owing to its high solubility in N-methyl pyrrolidone (NMP), it was interesting to apply as polymer matrix for solvent-exchanged in situ forming gel. The aim of this research was to prepare in situ forming gels from ERS to deliver the antimicrobial agents (doxycycline hyclate, metronidazole, and benzoyl peroxide) for periodontitis treatment. They were evaluated for viscosity and rheology, gel formation, syringeability, drug release, and antimicrobial activities. The solvent exchange between NMP and an external aqueous simulated gingival crevicular fluid stimulated the dissolved ERS transforming into the opaque rigid gel. Antimicrobial agent loaded ERS systems exhibited Newtonian flow with acceptable syringeability. The higher-loaded ERS promoted the more prolongation of drug release because of the retardation of water diffusion into the precipitated matrix. Antimicrobial activities against Staphylococcus aureus, Escherichia coli, Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis depended on type of drugs and test microorganisms. Doxycycline hyclate loaded ERS systems showed these activities greater than the others; however, all of them could inhibit all test microorganisms. Thus, the solvent exchange-induced in situ forming gels comprising ERS-antimicrobial drugs exhibited potential use as localized delivery systems for periodontitis treatment.

Cyclodextrin–poloxamer aggregates as nanocarriers in eye drop formulations: dexamethasone and amphotericin B

Abstract In this present study cyclodextrin (CD)–poloxamer aggregates were characterized and developed as ophthalmic drug carriers. The combined effect of γCD/2-hydroxypropyl-γCD (HPγCD) mixtures and poloxamer on solubilization and permeability of two model drugs, dexamethasone (Dex) and amphotericin B (AmB), was investigated. The CD–poloxamer interaction and complex aggregation were examined by 1H nuclear magnetic resonance (1H-NMR), their solubilizing ability by high-performance liquid chromatography, and their particle size determined by dynamic light scattering and transmission electron microscopy. Formulations containing either 1.5% w/v Dex or 0.15% w/v AmB in eye drop suspensions containing various γCD/HPγCD ratios and poloxamer 407 (P407) were prepared. The solubility of the drugs, surface tension and hemolytic effect of the eye drops and drug permeation from selected formulations were determined. The 1H-NMR study showed that P407 formed inclusion complex with CDs by inserting its poly(propylene oxide) segment into the CD cavity. P407 and γCD interacted with each other to form nanosized aggregates, and the observed concentration of dissolved γCD and P407 progressively decreased with increasing γCD and P407 concentrations. Including a high proportion of HPγCD improved the drug solubilization and reduced the hemolytic effect. The surface tension of the formulations decreased with increasing P407 concentration. Furthermore, increasing P407 content in the formulations enhanced formation of complex aggregates with consequent slower drug release. It was concluded that the drug/γCD/HPγCD complex was stabilized by P407 through formation of multi-component aggregates. Thus, CD–poloxamer aggregates are self-assembled nanocarriers from which drug delivery characteristics can be adjusted by changing the γCD/HPγCD/P407 ratios.

Transdermal nicotine mixed natural rubber-hydroxypropylmethylcellulose film forming systems for smoking cessation: in vitro evaluations

Abstract Novel film forming polymeric dispersions for transdermal nicotine delivery were prepared from deproteinized natural rubber latex (DNRL) blended with hydroxypropylmethylcellulose (HPMC) and dibutyl phthalate (DBP) or glycerin (GLY) as plasticizer. The preliminary molecular compatibility of ingredients was observed by Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry characterizations. All film forming polymeric dispersions were elegant in appearance and smooth in texture without agglomeration. Their pH was 7–8. In addition, their viscosity and spreadability showed good characteristics depended on HPMC and plasticizers blended. The transparent in situ dry films with good strength and elasticity were also confirmed by peeling-off. The nicotine release from them revealed an initial fast release that was similar to the release from a concentrated nicotine solution, and followed by slow release pattern from the in situ films. GLY blended formulation produced a higher amount of nicotine permeation through the in vitro pig skin than DBP blends. Ethanol mixing also enhanced nicotine permeation, but it affected the integrity of in situ films. The nicotine release and skin permeation kinetics were by a diffusion mechanism that was confirmed by the Higuchis model. These formulations were safe without producing any severe skin irritation. However, for the stability they needed to be stored at 4 °C in tightly sealed containers.

Thermal and Mechanical Properties of Natural Rubber/Rice Starch Interpenetrating Network Hydrogel

Novel hydrogels based on natural rubber latex (NRL) and rice starch (RSt) (1:2 ratio) were prepared with various amount of N,N-methylenebisacrylamide (MBA) and 2.5 phr of maleic acid to form interpenetrating networks (IPN) using free-radical polymerization technique. The thermal and mechanical properties were performed by differential scanning calorimetry and mechanical tests. From data obtained, the change in Tg of rubber and melting point of RSt indicated that polymer-polymer interaction could be formed in IPN hydrogel. The higher amount addition of MBA created more mechanical strength of IPN hydrogels caused by the higher of interlacement formation. However, their mechanical strength of such hydrogels was lower than that of NRL alone due to the formation of amorphous structure in IPN hydrogel. These IPN hydrogels also improved the swelling property which will be utilized for wound healing application.