Investigation of the Performance of the Disintegration Test for Dietary Supplements

The aim of this study was to investigate how beaker size, basket assembly, use of disk, and immersion medium impact the disintegration time of dietary supplements. The disintegration times were determined for five tablet and two capsule products. A two-station disintegration tester was used with Apparatus A or Apparatus B as described in the United States Pharmacopeia (USP) chapters, < 701 > and < 2040 >. Two beakers complying with the harmonized specifications were used, one with a volume of 1,000 mL and one with a 1,500-mL volume. The disintegration data were analyzed using ANOVA for the following factors: beaker size, equipment (App A and B) and condition (with/without disk). Two tablet products were not sensitive to any changes in the test conditions or equipment configurations. One product was only partially sensitive to the test conditions. The other products showed impact on the disintegration time for all test conditions. The results revealed that these tablet products might pass or fail current USP disintegration requirements depending on the equipment configuration. Similar results were obtained for the two investigated capsule formulations. One product might fail current USP disintegration requirements if the large beaker was used, but might pass the disintegration requirements when the small beaker was used. Hydroxy propyl methyl cellulose capsules were mostly influenced if sodium instead of a potassium buffer was used as the immersion medium. The results demonstrate that the current harmonized ICH specifications for the disintegration test are insufficient to make the disintegration test into reliable test for dietary supplements.

SENSORY APPROACH TO MEASURE FRAGRANCE INTENSITY ON THE SKIN

Sensory analysis is a precise and descriptive measuring technique to quantify human responses to stimuli. Odor, one of these stimuli, is basically the result of the interaction between a chemical stimulus and the olfactory receptor system, which can be described using a number of different dimensions and measures through different sensory tests: threshold, intensity and quality. To measure fragrance performance on the skin, these parameters are very important, but the main attribute to be evaluated is substantivity, thus the importance of the sensory scale chosen to measure perception, discriminate different intensities and determine the substantivity of the fragrance. Some studies comparing the labeled magnitude scale (LMS) with other magnitude scales and their derivations showed that the use of the LMS scale to measure fragrance intensity could semantically understand the intensity of the stimulus. Tests using this scale confirmed the applicability and efficiency of the LMS. PRACTICAL APPLICATIONS The objective of this article is to review the techniques used to measure odor and fragrance intensities applied on the skin. The review shows general sensory techniques and their goals, the newest olfactory mechanism and its contribution to sensory evaluation and which attributes should be considered to measure odor. Substantivity/retentivity or longevity can be regarded as the most important attributes if you want to measure fragrance performance on the skin. Past studies showed different scales tested to measure odor, and some of them demonstrated that the labeled magnitude scale is very suitable to measure fragrance on the skin.

Quantitative Determination of Dimethylaminoethanol in Cosmetic Formulations by Nuclear Magnetic Resonance Spectroscopy

A nuclear magnetic resonance (NMR) spectroscopic method was validated for the quantitative determination of dimethylaminoethanol (DMAE) in cosmetic formulations. The linearity in the range from 0.5000 to 1.5000 g (DMAE salt/mass maleic acid) presents a correlation coefficient > 0.99 for all DMAE salts. The repeatability (intraday), expressed as relative standard deviation, ranged from 1.08 to 1.44% for samples and 1.31 to 1.88% for raw materials. The detection limit and quantitation limit were 0.0017 and 0.0051 g for DMAE, 0.0018 and 0.0054 g for DMAE bitartrate, and 0.0023 and 0.0071 g for DMAE acetamidobenzoate, respectively. The proposed method is simple, precise, and accurate and can be used in the quality control of raw materials and cosmetic gels containing these compounds as active substances.

Quantitative Determination of Gemifloxacin Mesylate in Tablets by Capillary Zone Electrophoresis and High Performance Liquid Chromatography

The aim of this study was to develop and validate selective and sensitive methods for quantitative determination of an antibacterial agent, gemifloxacin, in tablets by high performance liquid chromatography (HPLC) and capillary zone electrophoresis (CZE). The HPLC method was carried out on a LiChrospher (R) 100 RP-8e, 5 mu m (125 x 4 mm) column with a mobile phase composed of tetrahydrofuran-water (25:75, v/v) with 0.5 % of triethylamine and pH adjusted to 3.0 with orthophosphoric acid. The CZE method was performed using 50 mM sodium tetraborate buffer (pH 8.6). Samples were injected hydrodynamicaly (0.5 psi, 5 s) and the electrophoretic system was operated under normal polarity, at +20 kV and capillary temperature of 18 degrees C. A fused-silica capillary 40.2 cm (30 cm effective length) x 75 mu m i.d. was used. Both, HPLC and CZE could be interesting and efficient techniques to be applied for quality control in pharmaceutical industries.

Development and validation of a method for quantitative determination of econazole nitrate in cream formulation by capillary zone electrophoresis

A simple, fast, inexpensive and reliable capillary zone electrophoresis (CZE) method for the determination of econazole nitrate in cream formulations has been developed and validated. Optimum conditions comprised a pH 2.5 phosphate buffer at 20 mmol L(-1) concentration, +30 kV applied voltage in a 31.5 cm x 50 mu m I.D. capillary. Direct UV detection at 200 nm led to an adequate sensitivity without interference from sample excipients. A single extraction step of the cream sample in hydrochloric acid was performed prior to injection. Imidazole (100 mu g mL(-1)) was used as internal standard. Econazole nitrate migrates in approximately 1.2 min. The analytical curve presented a coefficient of correlation of 0.9995. Detection and quantitation limits were 1.85 and 5.62 mu g mL(-1), respectively. Excellent accuracy and precision were obtained. Recoveries varied from 98.1 to 102.5% and intra- and inter-day precisions, calculated as relative standard deviation (RSD), were better than 2.0%. The proposed CZE method presented advantageous performance characteristics and it can be considered suitable for the quality control of econazole nitrate cream formulations. (c) 2008 Elsevier B.V. All rights reserved.

Molecular modeling and QSAR studies of a set of indole and benzimidazole derivatives as H(4) receptor antagonists

Histamine is an important biogenic amine, which acts with a group of four G-protein coupled receptors (GPCRs), namely H(1) to H(4) (H(1)R - H(4)R) receptors. The actions of histamine at H(4)R are related to immunological and inflammatory processes, particularly in pathophysiology of asthma, and H(4)R ligands having antagonistic properties could be helpful as antiinflammatory agents. In this work, molecular modeling and QSAR studies of a set of 30 compounds, indole and benzimidazole derivatives, as H(4)R antagonists were performed. The QSAR models were built and optimized using a genetic algorithm function and partial least squares regression (WOLF 5.5 program). The best QSAR model constructed with training set (N = 25) presented the following statistical measures: r (2) = 0.76, q (2) = 0.62, LOF = 0.15, and LSE = 0.07, and was validated using the LNO and y-randomization techniques. Four of five compounds of test set were well predicted by the selected QSAR model, which presented an external prediction power of 80%. These findings can be quite useful to aid the designing of new anti-H(4) compounds with improved biological response.

Influence of storage temperature on cooling intensity of topical emulsions containing encapsulated menthol

The cooling intensity of topical emulsions added with encapsulated or free menthol was evaluated by a screened and trained panel recruited based on the American Society for Testing and Materials method. A sensory panel composed of 10 trained judges performed the evaluation of samples stored at 22 +/- 2C for 24 h and, after 28 days of storage, at 37.0 +/- 0.5C. The obtained data were analyzed by analysis of variance and Tukey`s test. The results showed an increase of cooling intensity as a function of encapsulated menthol concentration. The opposite was observed in samples added with free menthol, which may have caused sensory fatigue. Storage at 37 +/- 0.5C for 28 days had no impact on the cooling intensity of emulsions containing encapsulated menthol, demonstrating high stability and suggesting its application in cooling skin care products. In contrast, emulsions added with free menthol showed a drastic decrease of cooling intensity at 37 +/- 0.5C..

Influence of Lactobacillus paracasei and inulin on instrumental texture and sensory evaluation of fresh cream cheese

The influence of the addition of a potential probiotic culture of Lactobacillus paracasei and of the prebiotic fiber inulin on the texture profile and on the sensory evaluation of probiotic and synbiotic fresh cream-cheeses was monitored. Three cheese-making trials were prepared in quintuplicate, all supplemented with a Streptococcus thermophilus starter culture (T1, T2 and T3). L. paracasei subsp. paracasei was added to T1 and T2, and inulin, to T2. The instrumental texture profile was determined after 1, 7, 14 and 21 days of storage of the cheeses. Sensory evaluation was performed after 7 days of storage. The presence of Lactobacillus paracasei in cheeses T1 and T2 and of inulin in cheeses T2 did not alter the texture profile significantly. Cheeses T1 were the least preferred in the sensory evaluation and differed signifcantly from T2 and T3, due to acidic taste, according to panelists. On the other hand, T2 was the most preferred one, though not significantly different from T3. The addition of the prebiotic ingredient inulin to fresh cream cheese processed with a potentially probiotic Lactobacillus paracasei strain resulted in a product with appropriate features and with aggregated functional properties.

LACTOBACILLUS ACIDOPHILUS AND BIFIDOBACTERIUM SP IN CO-CULTURE IMPROVE SENSORY ACCEPTANCE OF POTENTIALLY PROBIOTIC PETIT-SUISSE CHEESE

Sensory acceptance of four trials of probiotic petit-suisse cheese was investigated. Cheeses were prepared using Streptococcus thermophilus TA 040 as starter not supplemented with any probiotic culture (T1-control), Lactobacillus acidophilus La-5 (T2), Bifidobacterium animalis subsp. lactis BL04 (T3) and L. acidophilus + B. animalis subsp. lactis (T4). Sensory acceptance tests were performed after 7 and 14 days of storage at 4 +/- 1 degrees C, using a 9-point hedonic scale to evaluate flavour, texture and overall acceptability. The population of La-5 and BL04 remained at 7.0 log CFU g(-1) and at 8.0 log CFU g(-1), respectively, during storage for up to 28 days. After 7 and 14 days of storage, cheese T4 presented the highest sensory acceptance for all attributes evaluated and differed significantly from the other cheeses (P<0.05). After 14 days of storage, cheese T3 presented the lowest acceptance and differed significantly from the other cheeses (P<0.05). The supplementation of petit-suisse cheese T4 with both La-5 and BL04 in co-culture with a starter culture resulted in a product with high probiotic populations during storage and excellent sensory acceptance. The results also showed that, when added separately, La-5 and BL04 did not affect the sensory acceptability of petit-suisse cheese.

Determination of chlorpheniramine in human plasma by HPLC-ESI-MS/MS: application to a dexchlorpheniramine comparative bioavailability study

In the present study a fast, sensitive and robust validated method to quantify chlorpheniramine in human plasma using brompheniramine as internal standard (IS) is described. The analyte and the IS were extracted from plasma by LLE (diethyl ether-dichloromethane, 80:20, v/v) and analyzed by HPLC-ESI-MS/MS. Chromatographic separation was performed using a gradient of methanol from 35 to 90% with 2.5 mm NH(4)OH on a Gemini Phenomenex C(8) 5 mu m column (50 x 4.6 mm i.d.) in 5.0 min/run. The method fitted to a linear calibration curve (0.05-10 ng/mL, R > 0.9991). The precision (%CV) and accuracy ranged, respectively: intra-batch from 1.5 to 6.8% and 99.1 to 106.6%, and inter-batch from 2.4 to 9.0%, and 99.9 to 103.1%. The validated bioanalytical procedure was used to assess the comparative bioavailability in healthy volunteers of two dexchlorpheniramine 2.0 mg tablet formulations (test dexchlorpheniramine, Eurofarma, and reference Celestamine (R), Schering-Plough). The study was conducted using an open, randomized, two-period crossover design with a 2 week washout interval. Since the 90% confidence interval for C(max) and AUC ratios were all within the 80-125% interval proposed by ANVISA and FDA, it was concluded that test and reference formulations are bioequivalent concerning the rate and the extent of absorption. Copyright (C) 2009 John Wiley & Sons, Ltd.

Development and Validation of Stability-Indicating HPLC Methods for Quantitative Determination of Pravastatin, Fluvastatin, Atorvastatin, and Rosuvastatin in Pharmaceuticals

High-performance liquid-chromatographic (HPLC) methods were validated for determination of pravastatin sodium (PS), fluvastatin sodium (FVS), atorvastatin calcium (ATC), and rosuvastatin calcium (RC) in pharmaceuticals. Two stability-indicating HPLC methods were developed with a small change (10%) in the composition of the organic modifier in the mobile phase. The HPLC method for each statin was validated using isocratic elution. An RP-18 column was used with mobile phases consisting of methanol-water (60:40, v/v, for PS and RC and 70:30, v/v, for FVS and ATC). The pH of each mobile phase was adjusted to 3.0 with orthophosphoric acid, and the flow rate was 1.0mL/min. Calibration plots showed correlation coefficients (r)0.999, which were calculated by the least square method. The detection limit (DL) and quantitation limit (QL) were 1.22 and 3.08 mu g/mL for PS, 2.02 and 6.12 mu g/mL for FVS, 0.44 and 1.34 mu g/mL for ATC, and 1.55 and 4.70 mu g/mL for RC. Intraday and interday relative standard deviations (RSDs) were 2.0%. The methods were applied successfully for quantitative determination of statins in pharmaceuticals.

Effect of inulin and Lactobacillus paracasei on sensory and instrumental texture properties of functional chocolate mousse

BACKGROUND: This study evaluated the effect of a potentially probiotic bacteria (Lactobacillus paracasei subsp. paracasei LBC 82), added solely or together with the prebiotic ingredient inulin on instrumental texture attributes and sensory properties of a functional chocolate mousse during storage at 4 +/- 1 degrees C for up to 28 days. RESULTS: The addition of Lactobacillus paracasei resulted in a firmer and more adhesive chocolate mousse. This effect was intensified with the presence of inulin in the synbiotic formulation (5.24 N and -0.956 N, respectively, for firmness and adhesiveness after 28 days of storage) (P < 0.05). L. paracasei population did not vary (P > 0.05) during storage (always between 7.27 and 7.35 log cfu g(-1)), both for the probiotic and the synbiotic mousses. Synbiotic mousse differed from control and probiotic mousses during storage with respect to the color attribute. Moreover, both probiotic and synbiotic mousses presented taste, aroma and texture perceptions which were different from one another and from the control mousse after 14 and 21 days of storage. CONCLUSION: The use of inulin, together with the potentially probiotic strain of Lactobacillus paracasei subsp. paracasei, is advantageous, conferring potentially symbiotic potential to the chocolate mousse, as well as favorable texture and sensory properties. (c) 2008 Society of Chemical Industry.

Inulin and oligofructose improve sensory quality and increase the probiotic viable count in potentially synbiotic petit-suisse cheese

The influence of inulin, oligofructose and oligosaccharides from honey, combined in different proportions, on the consumers` sensory acceptance, probiotic viable count and fructan content of novel potentially synbiotic petit-suisse cheeses was investigated. Probiotic populations varied from 7.20 up to 7.69 log cfu g(-1) (Bifidobacterium animalis subsp. lactis) and from 6.08 up to 6.99 log cfu g(-1) (Lactobacillus acidophilus). The highest fructan contents were achieved by the cheese trials containing oligofructose and/or inulin (above 8.90 g 100 g(-1)). The control trial showed the lowest mean acceptance (6.63) after 28 days of refrigerated storage, whereas the highest acceptance (7.43) was observed for the trial containing 10 g 100 g(-1) oligofructose. Acceptance increased significantly during storage (P < 0.05) only for cheeses supplemented with oligoftuctose and/or inulin. Cheeses containing honey did not perform well enough compared to the cheeses with addition of inulin and/or oligofructose, and the best synbiotic petit-suisse cheese considering sensory and technological functional features was that containing oligofructose and inulin combined, therefore encouraging the commercial product use. (c) 2007 Swiss Society of Food Science and Technology. Published by Elsevier Ltd. All rights reserved.

Quantitative Determination of Amlodipine Besylate in Tablets by High Performance Liquid Chromatography and UV Spectrophotometry

The purpose of this study was to develop and validate analytical methods for determination of amlodipine besylate in tablets. Simple, accurate and precise liquid chromatographic and spectrophotometric methods are proposed. For the chromatographic method, the conditions were: a LiChrospher (R) 100 RP-18 Merck (R) (125 mm x 4.6 mm, 5 mu m) column; methanol/water containing 1 % of trietylamine adjusted to pH 5.0 with phosphoric acid (35:65) as mobile phase; a flow rate of 1.0 mL/min and UV detector at 238 nm. Linearity was in the range of 50.0 - 350.0 mu g/mL with a correlation coefficient (r) = 0.9999. For the spectrophotometric method, the first dilutions of samples were performed in methanol and the consecutives in ultrapure water. The quantitation was made at 364.4 nm. Linearity was determined within the range of 41.0 - 61.0 mu g/mL with a correlation coefficient (r) = 0.9996. Our results demonstrate that both methods can be used in routine analysis for quality control of tablets containing amlodipine besylate.

Relaxation evoked by extracellular Ca(2+) in rat aorta is nerve-independent and involves sarcoplasmic reticulum and L-type Ca(2+) channell

The perivascular nerve network expresses a Ca(2+) receptor that is activated by high extracellular Ca(2+) concentrations and causes vasorelaxation in resistance arteries. We have verified the influence of perivascular nerve fibers on the Ca(2+)-induced relaxation in aortic rings. To test our hypothesis, either pre-contracted aortas isolated from rats after sensory denervation with capsaicin or aortic rings acutely denervated with phenol were stimulated to relax with increasing extracellular Ca(2+) concentration. We also studied the role of the endothelium on the Ca(2+)-induced relaxation, and we verified the participation of endothelial/nonendothelial nitric oxide and cyclooxygenise-arachidonic acid metabolites. Additionally, the role of the sarcoplasmic reticulum, K(+) channels and L-type Ca(2+) channels on the Ca(2+)-induced relaxation were evaluated. We have observed that the Ca(2+)-induced relaxation is completely nerve independent, and it is potentiated by endothelial nitric oxide (NO). In endothelium-denuded aortic rings, indomethacin and AH6809 (PGF(2 alpha) receptor antagonist) enhance the relaxing response to Ca(2+). This relaxation is inhibited by thapsigargin and verapamil, while was not altered by tetraethylammonium. In conclusion, we have shown that perivascular nervous fibers do not participate in the Ca(2+)-induced relaxation, which is potentiated by endothelial NO. In endothelium-denuded preparations, indomethacin and AH6809 enhance the relaxation induced by Ca(2+). The relaxing response to Call was impaired by verapamil and thapsigargin, revealing the importance of L-type Ca(2+) channels and sarcoplasmic reticulum in this response. (c) 2008 Elsevier Inc. All rights reserved.