Novel computer optimization methodology for pharmaceutical formulations investigated by using sustained-release granules of indomethacin

A modified optimization technique, based on the response surface methodology, was developed for selecting pharmaceutical formulations. In general optimization methods, it is difficult to insure that the optimum formulation is strictly obtainable. Thus, the combined use of random number techniques and Andrews' plots with general optimization methods was investigated for seeking the optimum formulation. The method developed in this study was applied to the optimization of a sustained-release formulation based on the interpolymer complex of polyvinylpyrrolidone with carboxyvinyl polymer. Indomethacin was selected as a model drug for which sustained-release formulations are desirable. Experimental results obtained for the optimum formulation agreed well with the predictions, indicating the usefulness of this approach.     

Analysis of degradation mechanism of plasticized PVC under artificial aging conditions

A plasticized poly(vinyl chloride) (PVC) has the advantage of low cost, long-term stability and flame resistance among other commodity plastic, and has been in service as a product in railway field. However, the transition of the plasticizer concentration through the degrading condition and its relationship with the mechanical properties, the molecular motion, the appearance of surface and other properties was not clear. These relationships were studied by means of Rheovibron, pulse NMR, GC/MS, GPC, SEM and other methods. The bulk properties show similar change between weathering and thermal aging. In addition, the molecular chain was little influenced, however, the plasticizer concentration shows obviously different transition through each phase of aging conditions. According to the results of the observation of surface and section, different appearances between weathering and thermal aging were indicated and these appearances closely relate to the bulk properties. In conclusion, through the weathering condition, a stepwise flow out of inorganic components and plasticizer was presumable to be a main mechanism of the degradation. On the other hand, through the thermal aging condition, the rearrangement and aggregation of the molecular chain by the annealing effect were conceivable as the main mechanism of the degradation.     

The first total synthesis of (+/-)-arisugacin A, a potent, orally bioavailable inhibitor of acetylcholinesterase

The first convergent total synthesis of (+/-)-arisugacin A was accomplished by stereoselective construction of the arisugacin skeleton via a Knoevenagel-type reaction of an alpha,beta-unsaturated aldehyde with a 4-hydroxy 2-pyrone and stereoselective dihydroxylation followed by deoxygenation.     

Block copolymers derived from azobiscyanopentanoic acid. IV. Synthesis of a polyamide–polystyrene block copolymer

Polyamides 6.10 and 6.6 (PA^* 6.10 and 6.6) containing small amounts of ? N?N? units in the main chains were prepared by interfacial polycondensation between hexamethylenediamine and sebacoyl chloride or adipoyl chloride with addition of azobiscyanopentanoyl chloride. Polyamide–polystyrene block copolymers (PA-b-PSt) were then prepared by decomposition of the ? N?N? units of PA^*, initiating radical polymerization of styrene in m-cresol. The average PA block length of PA-b-PSt thus formed was longer than that expected from the initially present PA segments between the ? N?N? units. This is probably due to recombination of PA radicals whose initiation efficiency is as low as 15%. The PSt blocks also had higher molecular weight (7000–79,000) in comparison with homopolystyrene produced from monomeric azobiscyanopentanoic acid used as an initiator due to higher viscosity of polymerization system. Variation of intrinsic viscosity and turbidimetric titration behavior along with the change in composition were also discussed.     

Spontaneous copolymerization of 1,3-cycloheptadiene with acrylonitrile in the presence of zinc chloride

The reaction of 1,3-cycloheptadiene (1,3-CHpD) with acrylonitrile (AN) in the presence of ZnCl₂ leads spontaneously to the simultaneous formation of an alternating copolymer and a small amount of cycloadduct. The copolymer has a predominantly cis-1,4-structure. The formation of the charge—transfer complex between 1,3-CHpD and (AN)c (AN coordinated to ZnCl₂) in AN was detected by ultraviolet (UV) spectroscopy. The activation energies for the cycloaddition and for the copolymerization under the conditions used were determined to be 17.6 (in the presence of 1,1-diphenyl-2-picrylhydrazyl) and 16.3 kcal/mole, respectively. The rate of copolymerization in AN was found to depend on the 1.5th power of the concentrations of (AN)c and of 1,3-CHpD. Oxygen and UV irradiation causes an acceleration of the copolymerization only. On the basis of these results the mechanism of the spontaneous copolymerization is discussed and its relation to the cycloaddition in systems of 1,3-cyclodienes and AN in the presence of ZnCl₂ is mentioned.     

A spot test for ammonium ion by the color band formation method

Removing nutrients from wastewaters is important in controlling eutrophication. Processes for removing nutrients require accurate control of operational conditions, and it is necessary to monitor nutrient concentrations during the removal process. For this purpose, a simple and accurate analytical method is especially important for small-scale wastewater treatment facilities. Here, we report a simple colorimetric method for determining NH₄⁺-N in wastewater. The method is to detect NH₄⁺-N by a color band length formed in a minicolumn, and similar methods for heavy metals detection were reported by Morosanova et al. In this study, the length of the color band of indonaphthol dye trapped on an adsorbent in a minicolumn was linearly correlated with NH₄⁺-N concentration in the range 1-10 mg NH₄⁺-N l⁻¹ under optimized conditions. This methods was developed on the basis of our previously reported color band methods for orthophosphate and nitrite determination, but the adsorbent used in this work consisted of an admixture of synthetic hydrotalcite particles and poly(vinyl chloride) particles coated with equal amounts of benzylcetyldimethylammonium chloride and biphenyl. When the method was applied to actual wastewaters, the results corresponded well with the results obtained by the standard method, and suspended solids (SS) and dissolved organic pollutants did not interfere with detection.