Antioxidant and Anticholinesterase Activities in Various Parts of Sonneratia caseolaris (L.)

Cork tree, (Sonneratia caseolaris L.), family Sonneratiaceae, is a typical plant in mangroves. It is widespread in tropical and subtropical tideland throughout the World. It is reported to possess many medicinal properties. For searching new pharmacological activities of Cork tree, the total phenolic contents, antioxidant activities and the electric eel acetylcholinesterase inhibitions and the kinetics of extracts of various plant parts were determined. The graphs of trolox equivalent antioxidant capacity and ferric reducing antioxidant power of all extracts showed good linearity with P-value of slopes less than 0.05. The methanol extract of calyxs by maceration method and methanol extract of stamen by soxhlet method presented moderate trolox equivalent antioxidant capacity values. For ferric reducing antioxidant power assay, all extracts gave fair to low antioxidant activities. The tacrine, stamen extract and seed extract by maceration using methanol showed noncompetitive inhibition on acetylcholinesterase activity. While, luteolin, luteolin glycoside and calyx extract and seed extract by boiling using water presented partial noncompetitive inhibition on acetylcholinesterase activity.     

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.     

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.     

Modification of physicochemical and mechanical properties of shellac by partial hydrolysis

The shellac was modified by partial hydrolysis with 2.0% (w/w) NaOH for different times. The hydrolysed shellac was then evaluated for physicochemical and film properties in comparison with native shellac. The tablets coated with native and hydrolysed shellac were also evaluated. The results demonstrated that acid value (AV) of shellac increased with prolongation of hydrolysis time. The solubility of shellac in buffer solution (pH < or = 7) gradually increased with increasing hydrolysis time. The films prepared from hydrolysed shellac were more flexible and soft than those prepared from native shellac. The increasing of flexibility was correlated with the increasing of soft resin in shellac. The water vapor permeability of hydrolysed shellac film was lower than that of native shellac film. The higher acid permeability of the tablet coated with hydrolysed shellac was observed. In ethanol-based film coating, shellac had lower solubility and thus lower drug dissolution from coated tablets was observed. In ammonia-based film coating, the solubility of shellac was improved higher nearby pH 7.0 by an ammonium neutralisation method because of forming well-soluble salts, thereby higher drug dissolution was obtained. Partial hydrolysis provided modified shellac, which is more effective for ammonium salt formation, thus very higher drug dissolution was achieved in the ammonia-based coated tablets.     

Effect of chitosan salts and molecular weight on a nanoparticulate carrier for therapeutic protein

The objective of this study was to investigate the potential of chitosan salts as a carrier in the preparation of protein-loaded nanoparticles. Glutamic and aspartic acids were used to prepare chitosan salts of 35, 100, and 800 KDa. Nanoparticles of chitosan base, chitosan glutamate, and chitosan aspartate were produced by ionotropic gelation with sodium tripolyphosphate (TPP). Bovine serum albumin (BSA) was applied as a model protein at loading concentrations ranging from 0.2 to 2 mg/mL. The size of the nanoparticles, as measured by photon correlation spectroscopy, was in the range of 195 to 3450 nm, depending on type and molecular weight of chitosan. Nanoparticles prepared with higher molecular weight chitosan showed larger sizes. The encapsulation was controlled by the competition of BSA in forming ionic cross-linking with chitosan and by the entrapment of BSA during the gelation process. Higher BSA encapsulation efficiency (EE) was obtained for nanoparticles prepared with chitosan salts compared to those prepared with the base. The higher EE was a result of a higher degree of ionization, causing more active sites to interact with BSA. In addition, a higher and faster release of BSA from the nanoparticles into pH 7.4 buffer medium was observed for nanoparticles of the chitosan salts than was observed for nanoparticles of the chitosan base. The higher and faster release was attributed to higher EE and lower entrapment of BSA within the matrix of the nanoparticle during the gelation process. The influence of molecular weight on the property of nanoparticles exhibited different effects. The difference was a result of different organic acids used to prepare nanoparticles leading to the difference in polymer conformation and viscosity of organic acid solution. Therefore, this study showed that the characteristics of chitosan nanoparticles loaded with a protein drug could be readily modulated by changing the salt form or the molecular weight of the chitosan carrier.     

Characterization of chitosan acetate as a binder for sustained release tablets.

A chitosan derivative as an acetate salt was successfully prepared by using a spray drying technique. Physicochemical characteristics and micromeritic properties of spray-dried chitosan acetate (SD-CSA) were studied as well as drug-polymer and excipient-polymer interaction. SD-CSA was spherical agglomerates with rough surface and less than 75 microm in diameter. The salt was an amorphous solid with slight to moderate hygroscopicity. The results of Fourier transform infrared (FTIR) and solid-state (13)C NMR spectroscopy demonstrated the functional groups of an acetate salt in its molecular structure. DSC and TGA thermograms of SD-CSA as well as FTIR and NMR spectrum of the salt, heated at 120 degrees C for 12 h, revealed the evidence of the conversion of chitosan acetate molecular structure to N-acetylglucosamine at higher temperature. No interaction of SD-CSA with either drugs (salicylic acid and theophylline) or selected pharmaceutical excipients were observed in the study using DSC method. As a wet granulation binder, SD-CSA gave theophylline granules with good flowability (according to the value of angle of repose, Carr's index, and Hausner ratio) and an excellent compressibility profile comparable to a pharmaceutical binder, PVP K30. In vitro release study of theophylline from the tablets containing 3% w/w SD-CSA as a binder demonstrated sustained drug release in all media. Cumulative drug released in 0.1 N HCl, pH 6.8 phosphate buffer and distilled water was nearly 100% within 6, 16 and 24 h, respectively. It was suggested that the simple incorporation of spray-dried chitosan acetate as a tablet binder could give rise to controlled drug delivery systems exhibiting sustained drug release.     

Development of time-, pH-, and enzyme-controlled colonic drug delivery using spray-dried chitosan acetate and hydroxypropyl methylcellulose.

A colonic drug delivery with a new concept based on a combination of time-, pH-, and enzyme-controlled system was developed. Spray-dried chitosan acetate (CSA) prepared from low molecular weight chitosan was characterized. A combination of CSA and hydroxypropyl methylcellulose (HPMC) was used as new compression-coats for 5-aminosalicylic acid (5-ASA) tablets. Factors affecting in-vitro drug release, i.e. % weight ratio of coating polymers, enzyme activity, pH of media, and excipients in core tablets, were evaluated. The tablets compression-coated with HPMC:CSA at 60:40 and 50:50% weight ratio providing lag times about 5-6h were able to pass through the stomach (stage I, 0.1N HCl) and small intestine (stage II, pH 6.8, Tris-HCl). The delayed release was time- and pH-controlled owing to the swelling with gradual dissolving of CSA and HPMC in 0.1N HCl and the less solubility of CSA at higher pH. After reaching the colon (stage III, pH 5.0, acetate buffer), the dissolution of CSA at low pH triggered the drug release over 90% within 14h. Furthermore, the degradation of CSA by beta-glucosidase in the colonic fluid enhanced the drug release while adding the disintegrant or the osmotic agent in the core tablets would affect the drug release.     

Formation of shellac succinate having improved enteric film properties through dry media reaction.

The aim of this study was to improve enteric properties of shellac by the formation of succinate derivative through dry media reaction. Shellac and succinic anhydride were mixed and then co-ground by planetary ball mill. The ground mixture was then activated by heating for various times and washed for removal of excess succinic anhydride. The ground mixtures and the heat-activated mixtures were characterized by physical and chemical tests, including acid value, FTIR spectroscopy, (1)H NMR and (13)C NMR spectroscopy, thermal analysis and film properties. The results demonstrated that acid values of heat-activated shellac mixtures increased with the increase of annealing time, suggesting the presence of carboxylic acid moieties of succinate at shellac molecules. The results were in good agreement with the DSC thermograms. The melting peak of shellac disappeared after heating, while melting peak of succinic anhydride gradually decreased, suggesting the utilization of succinic anhydride for the esterification. The shellac succinate formation was also confirmed by (1)H NMR and (13)C NMR spectroscopies. Film prepared from shellac succinate showed improved solubility, especially at the pH of small intestine (5.8-6.7), as compared to native shellac. The shellac succinate film also demonstrated better mechanical property, in terms of increased flexibility. In conclusion, solid-state formation of shellac succinate ester, which had improved enteric properties, was easily accomplished under the concept of "green approach".     

Enhanced enteric properties and stability of shellac films through composite salts formation.

The objective of this study was to improve the properties of shellac by composite salts formation. The shellac samples were prepared in various salt forms by dissolving them with 2-amino-2-methyl-1-propanol (AMP) and ammonium hydroxide (AMN) at various ratios of AMP:AMN. The results demonstrated that aqueous solubility of the shellac salts was improved as the ratio of AMP:AMN increased. The absorbance ratio of the FTIR peaks assigned to CO stretching of carboxylate and carboxylic acid (ABS1556/ABS1716) was increased with the increase of the AMP fraction, suggesting that the solubility enhancement was due to more ionization of AMP salts. Moisture adsorption studies indicated that shellac salts were more hygroscopic as AMP content increased. After storage at 40 degrees C, 75% RH, the acid value and insoluble solid of AMP salts were relatively constant even after storage of up to 180 days, suggesting that AMP should protect polymerization. The ABS1556/ABS1716 values of the shellac salts were rapidly decreased after storage, especially for those consisting of a high percentage of AMN. Thus, AMP should bind much tighter at the carboxylate binding site as compared with AMN, resulting in more solubility and stability. In conclusion, optimized shellac properties could be easily accomplished by composite salts formation.