Namon Hirun

Experimental FTIR and theoretical studies of gallic acid–acetonitrile clusters

Gallic acid (3,4,5-trihydroxybenzoic acid, GA) has many possible conformers depending on the orientations of its three OH and COOH groups. The biological activity of polyphenolic compounds has been demonstrated to depend on their conformational characteristics. Therefore, experimental FTIR and theoretical studies of the GA-solvent clusters were performed to investigate the possible most favored conformation of GA. Acetonitrile (ACN) was selected as the solvent since its spectrum did not interfere with the OH stretching bands of GA. Also of importance was that these OH groups, in addition to the carboxyl group, of the GA are the most likely groups to interact with receptors. The solution of GA in the ACN solution was measured and the complex OH bands were deconvoluted to four component bands. These component bands corresponded to the three OH bands on the benzene ring and a broad band which is a combination band of mainly the OH of the COOH group and the inter- and intramolecular H-bonds from the OH groups on the ring. The conformations, relative stabilities and vibrational analysis of the GA monomers and the GA-ACN clusters were investigated using the B3LYP/6-311++G(2d,2p) method. Conformational analysis of the GA monomer yielded four most possible conformers, GA-I, GA-II, GA-III and GA-IV. These conformers were subsequently used for the study of the GA:ACN clusters at the 1:1, 1:2 and 1:4 mole ratios. The IR spectra of the most stable structures of these clusters were simulated and the vibrational wavenumbers of the OH and C=O groups were compared with those from the experiment. The FTIR component bands were comparable to the computed OH bands of the GA-I-(ACN)(2), GA-IV-(ACN)(2) and GA-I-(ACN)(4) clusters. Furthermore, the C=O stretching bands and the bands in the regions of 1800-1000 cm(-1) obtained by computing and the experiment were similar for these clusters. Thus, GA-I and GA-IV are the most preferable conformations of GA in ACN and perhaps in the polar environment around the receptor sites of GA.

Characterization of supramolecular gels based on β-cyclodextrin and polyethyleneglycol and their potential use for topical drug delivery

Novel gels were prepared by blending β-cyclodextrin and polyethyleneglycol (PEG) in the presence of K2CO3. The objective of this study was thus to characterize the gels using rheology, modulated temperature differential scanning calorimetry (MTDSC), turbidity measurements, and hot stage microscopy, and then investigate the potential use of the gel for topical drug delivery. Two types of supramolecular gels, GelL and GelH were prepared at a low temperature (below 50 °C) and at a high temperature (above 70 °C), respectively. Both gels were thermo-reversible. Upon heating, GelL could turn to GelH. Nevertheless, upon cooling, GelH that was more stable than GelL precipitated and GelL could not be reformed. GelL may form through simple complexation of polyethyleneglycol (PEG) with β-cyclodextrin in the presence of K2CO3. However, GelH may form a specific complex or a pseudopolyrotaxane gel. For pharmaceutical application, GelL was investigated instead of GelH because the forming temperature of this gel was close to the human body temperature. The interactions among diclofenac sodium (DS), a model drug, and the components of the gel were examined using FTIR. These interactions may include ionic attraction and hydrogen bonds between the carboxylate groups of DS and the hydroxyl groups of PEG or β-cyclodextrin and probably also the inclusion of the aromatic ring of DS into the cavity of β-cyclodextrin. Furthermore, the release and permeation of diclofenac from GelL were significantly greater than those from a commercial gel. Therefore, GelL may be useful for the topical delivery of drugs.

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.

3,4,5-Trihy-droxy-benzoic acid.

In the title compound, C7H6O5, the three hydroxy groups on the ring are oriented in the same direction. There are two intramolecular O—H⋯O hydrogen bonds in the ring. In the crystal, there are several intermolecular O—H⋯O hydrogen bonds and a short contact of 2.7150 (18) Å between the O atoms of the para-OH groups of adjacent molecules.

Characterization of freeze-dried gallic acid/xyloglucan.

Abstract Background: Tamarind seed xyloglucan (TSX) is generally used for drug delivery systems. Gallic acid (GA) possesses various pharmacological activities. It has a good solubility and bioavailability but short half-life. Purpose: To prepare a sustained-release of GA to overcome its relatively short half-life. GA was blended with TSX and freeze-dried. The physicochemical properties of freeze-dried GA and freeze-dried GA/TSX were characterized, and the release profiles of GA from these freeze-dried samples were investigated. Method: All freeze-dried samples were characterized by PXRD, spectroscopic and thermal analyses. The dissolution studies were performed according to the United States Pharmacopeia (USP) XXX. Results: According to FTIR, FT-Raman and 13C CP/MAS NMR, the spectra of freeze-dried GA were similar to that of the anhydrous form. Nevertheless, DRIFTS and DSC were able to differentiate these two forms. The crystallinity of GA in the freeze-dried GA/TSX was the same as that of the freeze-dried GA. DSC indicates that there were interactions between GA and TSX. It was of interest that a freeze-dried sample with low amount of GA, 0.2% GA/1% TSX was mostly in an amorphous form. Moreover, all freeze-dried GA/TSX preparations demonstrated a sustained-release of GA compared to GA alone. The freeze-dried 1% GA/1% TSX provided the best sustained-release of GA of up to 240 min. Conclusions: TSX could change a crystal form of a small molecule to a mostly amorphous form. It was of importance that the freeze-dried GA/TSX could effectively retard the release of GA. These samples may be able to overcome the limitation for the therapeutic use of GA due to its short biological half-life.

SAXS and ATR-FTIR studies on EBT–TSX mixtures in their sol–gel phases

Our previous study demonstrated that mixtures of tamarind seed xyloglucan (TSX) with appropriate concentrations of eriochrome black T (EBT) produced a gel that could be of benefit for medical use. Here, the sol-gel systems of various fresh and aged mixtures were further investigated using rheological measurements. The nanostructural changes of EBT-TSX sol-gel phases were analyzed using SAXS. The interactions between EBT and TSX in the sol and gel states were examined using ATR-FTIR. SAXS data analysis demonstrated that the mixture containing lower concentration of EBT formed rod-like structures and that with higher concentrations of EBT produced flat particles. The sizes of the TSX structures from the aged mixtures in the gel stage were larger than those from the same mixtures in the sol state. ATR-FTIR spectral changes revealed that the azo and sulfonic acid groups of EBT interacted with the TSX, and the characteristic spectrum of the sulfonic acid group of EBT could discriminate between the sol and gel state of the EBT-TSX systems. The interactions between EBT and TSX may cause conformational changes to TSX and facilitate the sol-gel transition or formation of a gel.

Thermosensitive Poloxamer 407/Poly(Acrylic Acid) Hydrogels with Potential Application as Injectable Drug Delivery System

Thermosensitive hydrogels are of great interest for in situ gelling drug delivery. The thermosensitive vehicle with a gelation temperature in a range of 30–36°C would be convenient to be injected as liquid and transform into gel after injection. To prepare novel hydrogels gelling near body temperature, the gelation temperature of poloxamer 407 (PX) were tailored by mixing PX with poly(acrylic acid) (PAA). The gelation behaviors of PX/PAA systems as well as the interaction mechanism were investigated by tube inversion, viscoelastic, shear viscosity, DSC, SEM, and FTIR studies. The gelation temperature of the plain PX solutions at high concentration of 18, 20, and 22% (w/w) gelled at temperature below 28°C, which is out of the suitable temperature range. Mixing PX with PAA to obtain 18 and 20% (w/w) PX with 1% (w/w) PAA increased the gelation temperature to the desired temperature range of 30–36°C. The intermolecular entanglements and hydrogen bonds between PX and PAA may be responsible for the modulation of the gelation features of PX. The mixtures behaved low viscosity liquid at room temperature with shear thinning behavior enabling their injectability and rapidly gelled at body temperature. The gel strength increased, while the pore size decreased with increasing PX concentration. Metronidazole, an antibiotic used for periodontitis, was incorporated into the matrices, and the drug did not hinder their gelling ability. The gels showed the sustained drug release characteristic. The thermosensitive PX/PAA hydrogel could be a promising injectable in situ gelling system for periodontal drug delivery.

Microphase Separation and Gelation of Methylcellulose in the Presence of Gallic Acid and NaCl as an In Situ Gel-Forming Drug Delivery System

Novel hydrogels of methylcellulose (MC) with gallic acid (GA) and NaCl were developed for an in situ gel-forming delivery system. Plain MC and GA/NaCl/MC were characterized using micro-differential scanning calorimetry (micro-DSC), rheological and turbidity methods. The gelation temperatures of MC were reduced to body temperature with adding GA/NaCl. GA and NaCl caused slightly different effects on the gelation/degelation temperatures during heating/cooling, respectively, based on the different sensitivities of these three techniques. The gelation mechanism was investigated by UV spectrophotometry, and the hydrophobic interaction between the aromatic ring of GA and MC was verified. The NaCl/MC hydrogel had smaller micropores than GA/MC and MC, indicating a greater cross-linked density. Doxycycline (DX) was loaded into the systems and demonstrated a synergistic effect of DX/GA. Both GA and DX exhibited a sustained release. The hydrogel of GA/4NaCl/MC could be potentially used for the in situ delivery of DX for deep wound healing.