Liquid chromatographic method for identity, assay, and content uniformity of five tricyclic drugs

A liquid chromatographic (LC) procedure has been developed for the assay, content uniformity, and identification of single active ingredient solid and liquid formulations of amitriptyline, chlorpromazine, imipramine, thioridazine, and trifluoperazine. The drugs are extracted from their formulations with methanol or dilute hydrochloric acid, and identified by comparison of retention times with those of known standards; drugs are quantitated against these standards with dl-norephedrine hydrochloride as the internal standard. The precision of replicate injections is better than 2.5% for peak area and better than 1% for peak height. The precision of triplicate determinations of tablet composites is better than 2.2%.     

pH-induced difference spectrophotometric assay of acetazolamide, hydrochlorothiazide, and furosemide.

On the basis of pH-induced spectral changes for acetazolamide, hydrochlorothiazide, and furosemide, 3 different spectrophotometric methods are described. The methods were successfully applied to the assay of these drugs in different pharmaceutical formulations (tablets and ampoules). The accuracy of the analysis is increased by using the suggested methods as compared with conventional spectrophotometry.     

Environmentally friendly formulations of alachlor and atrazine: preparation, characterization, and reduced leaching

Atrazine and alachlor formulations were designed by encapsulating the herbicide molecules into phosphatidylcholine (PC) vesicles, which subsequently were adsorbed on montmorillonite. PC and montmorillonite are classified as substances of minimal toxicological risk by the U.S. EPA. PC enhanced alachlor and atrazine solubilities by 15- and 18-fold, respectively. A 6 mM PC:5 g/L clay ratio was found as optimal for PC adsorption on the clay. Active ingredient contents of the PC-clay formulations ranged up to 8.6% for atrazine and 39.5% for alachlor. Infrared spectroscopy showed hydrophobic interactions of herbicide molecules with the alkyl chains of PC, in addition to hydrophilic interactions with the PC headgroup. Release experiments in a sandy soil showed a slower rate from the PC-clay formulations than the commercial ones. Soil column experiments under moderate irrigation and bioactivity experiments indicate that a reduction in the recommended dose of alachlor and atrazine can be accomplished by using PC-clay formulations.     

Controlled release of isoproturon, imidacloprid, and cyromazine from alginate-bentonite-activated carbon formulations

Different alginate-based systems of isoproturon, imidacloprid, and cyromazine have been investigated in order to obtain controlled release (CR) properties. The basic formulation [sodium alginate (1.50%), pesticide (0.30%), and water] was modified using different amounts of bentonite and activated carbon. The higher values of encapsulation efficiency corresponded to those formulations prepared with higher percentages of activated carbon, showing higher encapsulation efficiency values for isoproturon and imidacloprid than for cyromazine, which has a higher water solubility. The kinetic experiments of imidacloprid/isoproturon release in water have shown us that the release rate is higher in imidacloprid systems than in those prepared with isoproturon. Moreover, it can be deduced that the use of bentonite and/or activated carbon sorbents reduces the release rate of the isoproturon and imidacloprid in comparison with the technical product and with alginate formulation without modifying agents. The highest decrease in release rate corresponds to the formulations prepared with the highest percentage of activated carbon. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, T50, were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the pesticide release data, the release of isoproturon and imidacloprid from the various formulations into water is controlled by a diffusion mechanism. The sorption capacity of the sorbents and the permeability of the formulations were the most important factors modulating pesticide release. Finally, a linear correlation of the T50 values and the content of activated carbon in formulations were obtained.     

Liquid chromatographic determination of prednisolone in tablets and bulk drugs: interlaboratory study

A normal phase liquid chromatographic (LC) method for the determination of prednisolone in tablets and bulk drugs was studied by 7 analysts. An LC system, consisting of a methanol-water-ethylene dichloride-acetic acid mobile phase and a silica column, was used to analyze bulk drugs, individual tablets, and composite samples. Analysts were supplied with 16 samples, including simulated formulations, composites of commercial tablets, intact tablets, and bulk drug substances. Results agreed with those obtained by the author. The coefficients of variation of the analysts' results ranged from 1.34% for bulk drugs to 2.14% for tablet composites. The LC method is suggested as an alternative to the official AOAC and USP XX blue tetrazolium colorimetric methods.     

Spectrophotometric determination of acetaminophen in tablets, sirups, and suppositories.

A differential spectrophotometric method and Glenn's method of orthogonal function are described for the assay of acetaminophen in tablets, sirups, and suppositories. Interference from excipients in the formulations is thereby avoided. Accuracy of the analyses is greater with the proposed methods than with the British Pharmacopoeia method.     

Slow-release formulation of a new biological pesticide, pyoluteorin, with mesoporous silica

A slow-release formula of potential biological pesticide Pyoluteorin (Plt) was prepared by using nanophase material of silicon dioxide loading drugs. The final experimental formula was m(Plt:Brij56:TMOS:HCl(aq)) = 0.04:1.4:2:1, synthesized by a highly ordered monolith (HOM) method. This formula can continuously release 85.13 ± 2.03 % of Plt within 28 days. A characterization study showed the formula formed a well-ordered mesoporous structure, with a surface area of 822 m(2) g(-1), with a measured mesoporous volume of 0.41 cm(3) g(-1) and a narrow distribution for the pore size centered at 2.4 nm. A bioactivity experiment showed it authentically prolonged the antifungal effects. This study is the first to report mesoporous formulations for biological pesticides and indicates a potentially interesting drug carrier. The association of a nanostructured silica to the molecular state of the drug holds great interests for field applications as it overcomes the rapid loss of biological function during drug utilities.     

Longevities and nitrogen,phosphorus, and potassium release patterns of polymer‐coated controlled‐release fertilizers at 30°C and 40°C

Abstract

The weekly nitrogen (N), phosphorus (P), and potassium (K) release from 17 polymer‐coated controlled‐release fertilizer (CRF) formulations of Nutricote, Apex Gold, Osmocote, and a 9‐month Macrocote were measured at 30.6±0.8°C and 40.0±1.5°C. Five grams of each CRF were placed at a depth of 50 mm in 280x50 mm acid washed then rinsed silica sand columns which were leached with deionized water three times each week until nutrient recovery ceased. The volume of leachate was recorded each week and subsampled for ammonium‐N, nitrate‐N, phosphate‐P, and K analyses. Each CRF treatment was replicated three times at each temperature. Nutrient release profiles were determined. Longevities, measured as weeks to 90% nutrient recovery, were considerably shorter than the nominated release periods for all formulations. Within each CRF product group, the longevity of 9 and 12 month formulations were similar with Apex Gold 12–14 month high nitrate having the longest (38 weeks for N at 30°C) and Osmocote 8–9 month the shortest (23 weeks for N at 30°C). There were consistent trends in the nutrient release periods across all CRFs with P>K>N and with differences of around 10% in duration between nutrients. The P:N release ratio exceeded 0.10 for most CRFs during the early release period indicating an adequate P supply for most plant species. The mean reduction in longevity for Nutricote, Apex Gold, and Osmocote formulations for an increase in incubation temperature from 30°C to 40°C was 19–21 % for N, 13–14% for P, and 14–15% for K. All CRFs released nutrients unevenly with the highest rate occurring during the early part of the release period. This pattern was accentuated at 40°C and by the shorter term release formulations. The nutrient release rates of all CRFs declined steadily after their maxima.     

Modeling of maximum dry density and optimum moisture content of stabilized soil using artificial neural networks

This study considers the use of artificial neural networks (ANNs) to predict the maximum dry density (MDD) and optimum moisture content (OMC) of soil‐stabilizer mix. Multilayer perceptron (MLP), one of the most widely used ANN architectures in the literature, is utilized to construct comprehensive and accurate models relating the MDD and OMC of stabilized soil to the properties of natural soil such as particle‐size distribution, plasticity, linear shrinkage, and the type and quantity of stabilizing additives. Five ANN models are constructed using different combinations of the input parameters. Two separate sets of ANN prediction models, one for MDD and the other for OMC, and also a combined ANN model for multiple outputs are developed using the potentially influential input parameters. Relative‐importance values of various inputs of the models are calculated to determine the significance of each of the predictor variables to MDD and OMC. Inferring the most relevant input parameters based on Garson's algorithm, modified ANN models are separately developed for MDD and OMC. The modified ANN models are utilized to introduce explicit formulations of MDD and OMC. A parametric study is also conducted to evaluate the sensitivity of MDD and OMC due to the variation of the most influencing input parameters. A comprehensive set of data including a wide range of soil types obtained from the previously published stabilization test results is used for training and testing the prediction models. The performance of ANN‐based models is subsequently analyzed and compared in detail. The results demonstrate that the accuracy of the proposed models is satisfactory as compared to the experimental results.     

Titrimetric determination of vitamin B6 using chloramine-T, bromamine-T, and bromamine-B

Simple titrimetric methods have been developed for determination of the vitamin pyridoxine (PRX) in solution, using aromatic N-haloamines, chloramine-T, bromamine-T, and bromamine-B. The method is based on oxidation of PRX by the N-haloamines; the oxidation involves a 2-electron change. The reaction products, pyridoxal and sulfonamides, were identified. The effects of variables, such as pH of the medium and the presence of foreign ions, and pyridoxal, pyridoxalamine, glycerol, and alcohol, on the rate of oxidation were studied. The methods are useful for determining PRX in pharmaceutical formulations and for assaying its cadmium complex. Statistical evaluation showed that analytical results are accurate to within 1%.     

Polymeric microcapsules of alachlor and metolachlor: preparation and evaluation of controlled-release properties.

The microencapsulation of alachlor and metolachlor in the polymers cellulose acetate butyrate, ethyl cellulose, poly(methyl methacrylate), and poly(alpha-methylstyrene) with different emulsifiers is described. The controlled-release properties of these formulations were measured under greenhouse conditions on barnyardgrass, crowfootgrass, smallflower morningglory, and Palmer amaranth. The emulsifiers had little effect on the activity of the herbicides. The herbicidal activities of the poly(methyl methacrylate) and poly(alpha-methylstyrene) formulations were consistently lower on all weed species when compared to the activities of the cellulose acetate butyrate, ethyl cellulose, and commercial formulations. The ethyl cellulose formulation of alachlor exhibited controlled-release properties. The results with metolachlor were similar to those with alachlor except that none of the metolachlor formulations exhibited efficacy superior to that of the commercial formulation or controlled release properties.     

Nanoemulsions of cancer chemopreventive agent benzyl isothiocyanate display enhanced solubility, dissolution, and permeability

Benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables, is an effective chemopreventive agent. The objective of this study was to develop nanoemulsion formulations for the oral delivery of BITC. Optimized oil-in-water BITC nanoemulsions were prepared by a spontaneous self-nanoemulsification method and a homogenization-sonication method. Both nanoemulsions entrapped high amounts of BITC (15-17 mg/mL), with low polydispersity and good colloidal stability. The BITC nanoemulsions showed enhanced solubility and dissolution compared to pure BITC. These formulations markedly increased the apical to basolateral transport of BITC in Caco-2 cell monolayers. The apparent permeability values were 3.6 × 10(-6) cm/s for pure BITC and (1.1-1.3) × 10(-5) cm/s for BITC nanoemulsions. The nanoemulsions were easily taken up by human cancer cells A549 and SKOV-3 and inhibited tumor growth in vitro. This work shows for the first time that BITC can be formulated into nanoemulsions and may show promise in enhancing absorption and bioavailability.     

Development of controlled release formulations of carbofuran and evaluation of their efficacy against Meloidogyne incognita

Controlled release (CR) formulations of the insecti-nematicide carbofuran have been prepared using commercially available rosin, sodium carboxymethylcellulose and sodium carboxymethylcellulose with clay (bentonite, kaolinite, and Fuller's earth). The kinetics of carbofuran release in soil from the different formulations were studied in comparison with that of the commercially available granules (3G). Release from the commercial formulation was faster than with the new CR formulations. Addition of clay in the biodegradable polymer matrix reduced the rate of release. The diffusion exponent (n value) of carbofuran in soil ranged from 0.462 to 0.740 in the tested formulations. The half-release (t1/2) values ranged between 4.79 and 25.11 days, and the period of optimum availability (POA) of carbofuran ranged from 15.10 to 43.97 days. The mean EC50 of the commercial formulation against Meloidogyne incognita was quite high as compared to those of CR formulations. The effective duration (te) of carbofuran from the CR and commercial formulations was predicted by fitting the mean EC50 values of test formulations in the model (M(infinity) - Me)/M(infinity) = Kdte. It was 0.7 day in commercial 3G in comparison with 17.8 days for CMC-bentonite. The bioassay studies revealed that with the rosin-yellow polymer, the dose of carbofuran could be reduced to half of its recommended dose for nematode control. Overall, a comparison of CR formulations with the commercial one showed an earlier degradation of carbofuran in the latter and relatively prolonged activity in the former.     

Norflurazon mobility, dissipation, activity, and persistence in a sandy soil as influenced by formulation

Five ethylcellulose (EC) microencapsulated formulations (MEFs) of norflurazon were prepared and applied in soil to study their mobility, dissipation, activity, and persistence. The results show that the release into water of norflurazon from EC microspheres was retarded when compared with that of commercial herbicide. The mobility of norflurazon from MEFs into soil columns has been greatly diminished in comparison with that of its current commercial formulation (CF). Norflurazon distribution at different depths in the soil was higher in the upper ring (up to 50% of the initial application). In contrast, the residues from commercial norflurazon along the complete soil column were only about 2%. Degradation and bioassay experiments showed that the MEFs had greater persistence (t1/2 values were 7.72 and 30.83 weeks for CF and MEFs, respectively) and herbicidal activity than the commercial formulation. The use of these formulations can be advantageous, because they can minimize the risk of groundwater contamination and permit herbicide use at reduced rates, maintaining the desired concentrations of herbicide in the topsoil layer for longer periods of weed control.     

Rapid liquid chromatographic determination of dimetridazole and ipronidazole in swine feed

A simple and rapid method is described for the determination of dimetridazole (DMZ) and ipronidazole (IPR) in swine feeds at various levels (0.11-110 ppm). The drugs are released from feed by prewetting with a buffer, followed by extraction with either methanol or methylene chloride, depending on the drug level; if necessary, an acid-base cleanup is used before the liquid chromatographic analysis. The analytes are separated on a C18 column and monitored at 320 nm for detection and quantitation. Recoveries of DMZ from several feed formulations averaged 108% at the 92.8 ppm level with a standard deviation (SD) of 4.00% and a coefficient of variation (CV) of 3.70%, 101% at the 11.2 ppm level with an SD of 11.9% and a CV of 11.8%, and 100% at the 0.112 ppm level with an SD of 9.27% and a CV of 9.25%. Recoveries of IPR averaged 77.1% at the 12.9 ppm level with an SD of 1.75% and a CV of 2.27%; IPR recoveries averaged 35.2% at the 0.129 ppm level with an SD of 3.39% and a CV of 9.63%.     

Phytoestrogen content of beverages, nuts, seeds, and oils

Phytoestrogens are secondary plant metabolites that have received increasing attention for their bioactivity, in particular due to their structural and functional similarity to 17beta-estradiol. Although urinary and plasma phytoestrogens can be used as biomarkers for dietary intake, this is often not possible in large epidemiological studies or in the assessment of general exposure in free-living individuals. Accurate information about dietary phytoestrogens is therefore important, but there are very limited data concerning food contents. In this study was analyzed a comprehensive selection of tea, coffee, alcoholic beverages, nuts, seeds, and oils for their phytoestrogen content using a newly developed sensitive method based on LC-MS incorporating (13)C 3-labeled standards. Phytoestrogens were detected in all foods analyzed, although the contents in gin and bitter (beer) were below the limit of quantification (1.5 microg/100 g). Lignans were the main type of phytoestrogens detected. Tea and coffee contained up to 20 microg/100 g phytoestrogens and beer (except bitter) contained up to 71 microg/100 g, mainly lignans. As these beverages are commonly consumed, they are a main source of dietary lignans. The results published here will contribute to databases of dietary phytoestrogen content and allow a more accurate determination of phytoestrogen exposure in free-living individuals.     

Characteristics and composition of watermelon, pumpkin, and paprika seed oils and flours

The nutritional quality and functional properties of paprika seed flour and seed kernel flours of pumpkin and watermelon were studied, as were the characteristics and structure of their seed oils. Paprika seed and seed kernels of pumpkin and watermelon were rich in oil and protein. All flour samples contained considerable amounts of P, K, Mg, Mn, and Ca. Paprika seed flour was superior to watermelon and pumpkin seed kernel flours in content of lysine and total essential amino acids. Oil samples had high amounts of unsaturated fatty acids with linoleic and oleic acids as the major acids. All oil samples fractionated into seven classes including triglycerides as a major lipid class. Data obtained for the oils' characteristics compare well with those of other edible oils. Antinutritional compounds such as stachyose, raffinose, verbascose, trypsin inhibitor, phytic acid, and tannins were detected in all flours. Pumpkin seed kernel flour had higher values of chemical score, essential amino acid index, and in vitro protein digestibility than the other flours examined. The first limiting amino acid was lysine for both watermelon and pumpkin seed kernel flours, but it was leucine in paprika seed flour. Protein solubility index, water and fat absorption capacities, emulsification properties, and foam stability were excellent in watermelon and pumpkin seed kernel flours and fairly good in paprika seed flour. Flour samples could be potentially added to food systems such as bakery products and ground meat formulations not only as a nutrient supplement but also as a functional agent in these formulations.     

Derivative spectrophotometric determination of some corticosteroids in combinations with other drugs

Three 2-component mixtures, namely, dexamethazone-chlorpheniramine maleate, prednisolone-chlorpheniramine maleate, and prednisolone-salicylic acid, have been assayed using their first (D1) and second (D2) derivative spectra in methanol, delta absorption (delta A), and second derivative of delta A (delta D2) spectra in methanol-methanolic HCl. In the first 2 mixtures, chlorpheniramine maleate was determined by measuring its delta D2 value at 278 nm, while dexamethazone and prednisolone were analyzed by measuring their D1 values at 248 nm. Prednisolone and salicylic acid were analyzed in combination by using their respective D2 spectral responses at 272 and 314 nm. The results obtained are reasonably reproducible with a relative standard deviation less than 2%. The method has been successfully applied to the analysis of these drugs in their pharmaceutical formulations.     

Simultaneous differential pulse polarographic determination of cadmium, lead, and copper in milk and dairy products

The contents of potentially toxic elements lead and cadmium and the essential element copper in various milk and dairy products consumed in Turkey were determined by differential pulse polarography (DPP), primarily to assess whether the intakes comply with recommended desired concentrations for essential and permissible levels for toxic elements. A simple and rapid DPP method has been developed for the simultaneous determination of cadmium, lead, and copper in samples. Using the differential pulse mode, half-wave peak potentials as E(1/2) were -0.58, -0.40, and -0.07 V for cadmium (Cd), lead (Pb), and copper (Cu), respectively. Marketed formulations of dairy products have been analyzed by calibration and standard addition methods. Recovery experiments were found to be quantitative. The linear domain ranges were 0.00-674.28 microg/L for Cd (R2 = 0.9999), 0.19-2.94 mg/L (p < 0.01) for Pb (R2 = 0.9997), and 0.41-133.46 microg/L for Cu (p < 0.01) (R2 = 0.9999). The studies have shown that the method is a rapid, reproducible, and accurate determination of these elements in milk and dairy products and can be used in the analysis of marketed formulations in the milk and dairy industry.     

Nonprotein amino acids of plants: significance in medicine,nutrition, and agriculture

Those nonprotein amino acids found in food and fodder plants and known to be toxic to man and domestic animals are described. These include toxins from many legume genera including Lathyrus, from other higher plant families, from seaweeds, and from fungi. Some inhibit protein synthesis, while others are incorporated into proteins with toxic effects. Basic processes such as urea synthesis and neurotransmission may be disrupted. The probable roles of nonprotein amino acids in protecting plants against predators, pathogens, and competing plant species are considered. The need to learn more of the nutritive value of nontoxic nonprotein amino acids and to explore the potential of others either as drugs or as leads to drugs in human and veterinary medicine is emphasized.