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Sample records for deodorant drug products

  1. Deodorants

    DEFF Research Database (Denmark)

    Svedman, C; Bruze, M; Johansen, J D

    2003-01-01

    Axillary dermatitis is a common problem, particularly in individuals with contact allergy to fragrances. Many individuals suspect their deodorant to be the causal product of their fragrance allergy. It has been shown that deodorants containing cinnamic aldehyde (cinnamal) can elicit axillary derm...

  2. Deodorants

    DEFF Research Database (Denmark)

    Bruze, Magnus; Johansen, Jeanne D; Andersen, Klaus Ejner

    2005-01-01

    Axillary dermatitis is common and overrepresented in people with contact allergy to fragrances. Many people suspect their deodorants to be the incriminating products. In order to investigate the significance of isoeugenol in deodorants for the development of axillary dermatitis when used by people...... with and without contact allergy to isoeugenol, patch tests with deodorants and ethanol solutions with isoeugenol, as well as repeated open application tests (ROAT) with roll-on deodorants with and without isoeugenol at various concentrations, were performed in 35 dermatitis patients, 10 without and 25...... with contact allergy to isoeugenol. A positive ROAT was observed only in patients hypersensitive to isoeugenol (Pdeodorants containing isoeugenol had been applied (PDeodorants containing isoeugenol in the concentration range of 0.0063-0.2% used 2 times daily...

  3. Deodorants

    DEFF Research Database (Denmark)

    Johansen, J D; Rastogi, Suresh Chandra; Bruze, M

    1998-01-01

    Deodorants are one of the most marketed types of cosmetics and are frequently reported as a cause of dermatitis, particularly among fragrance-sensitive persons. The aim of this study was to investigate the ability of deodorants, which had previously caused axillary dermatitis in fragrance......-mix-sensitive eczema patients, to provoke reactions on repeated open application tests on the upper arm and in the axillae, and to relate the findings to the content of fragrance-mix constituents in those deodorants. 14 eczema patients performed a 7-day use test with 1 or 2 deodorants that had caused a rash within...... the last 12 months. 2 applications per day were made in the axilla and simultaneously on a 25 cm2 area on the upper arm. A total of 20 deodorants were tested among the 14 patients. Afterwards, the deodorants were subjected to quantitative chemical analysis identifying constituents of the fragrance mix. 12...

  4. Deodorants

    DEFF Research Database (Denmark)

    Johansen, Jeanne Duus; Rastogi, S C; Bruze, M

    1998-01-01

    Deodorants are one of the most marketed types of cosmetics and are frequently reported as a cause of dermatitis, particularly among fragrance-sensitive persons. The aim of this study was to investigate the ability of deodorants, which had previously caused axillary dermatitis in fragrance-mix-sen...

  5. Health Risk Assessment on Hazardous Ingredients in Household Deodorizing Products

    Directory of Open Access Journals (Sweden)

    Minjin Lee

    2018-04-01

    Full Text Available The inhalation of a water aerosol from a humidifier containing disinfectants has led to serious lung injuries in Korea. To promote the safe use of products, the Korean government enacted regulations on the chemicals in various consumer products that could have adverse health effects. Given the concern over the potential health risks associated with the hazardous ingredients in deodorizing consumer products, 17 ingredients were analyzed and assessed according to their health risk on 3 groups by the application type in 47 deodorizing products. The risk assessment study followed a stepwise procedure (e.g., collecting toxicological information, hazard identification/exposure assessment, and screening and detailed assessment for inhalation and dermal routes. The worst-case scenario and maximum concentration determined by the product purpose and application type were used as the screening assessment. In a detailed assessment, the 75th exposure factor values were used to estimate the assumed reasonable exposure to ingredients. The exposed concentrations of seven ingredients were calculated. Due to limitation of toxicity information, butylated hydroxyl toluene for a consumer’s exposure via the dermal route only was conducted for a detailed assessment. This study showed that the assessed ingredients have no health risks at their maximum concentrations in deodorizing products. This approach can be used to establish guidelines for ingredients that may pose inhalation and dermal hazards.

  6. Health Risk Assessment on Hazardous Ingredients in Household Deodorizing Products

    Science.gov (United States)

    Lee, Minjin; Kim, Joo-Hyon; Lee, Daeyeop; Kim, Jaewoo; Lim, Hyunwoo; Seo, Jungkwan; Park, Young-Kwon

    2018-01-01

    The inhalation of a water aerosol from a humidifier containing disinfectants has led to serious lung injuries in Korea. To promote the safe use of products, the Korean government enacted regulations on the chemicals in various consumer products that could have adverse health effects. Given the concern over the potential health risks associated with the hazardous ingredients in deodorizing consumer products, 17 ingredients were analyzed and assessed according to their health risk on 3 groups by the application type in 47 deodorizing products. The risk assessment study followed a stepwise procedure (e.g., collecting toxicological information, hazard identification/exposure assessment, and screening and detailed assessment for inhalation and dermal routes). The worst-case scenario and maximum concentration determined by the product purpose and application type were used as the screening assessment. In a detailed assessment, the 75th exposure factor values were used to estimate the assumed reasonable exposure to ingredients. The exposed concentrations of seven ingredients were calculated. Due to limitation of toxicity information, butylated hydroxyl toluene for a consumer’s exposure via the dermal route only was conducted for a detailed assessment. This study showed that the assessed ingredients have no health risks at their maximum concentrations in deodorizing products. This approach can be used to establish guidelines for ingredients that may pose inhalation and dermal hazards. PMID:29652814

  7. Evaluation of radiation exposure from shoe-deodorants as radioactive consumer products

    International Nuclear Information System (INIS)

    Furuta, Etsuko; Yokota, Shigeaki; Aburai, Tamaru; Yoshizawa, Yukio

    2007-01-01

    Six shoe-deodorants on the market were analyzed using gamma-ray spectroscopy and radionuclide imaging techniques. The results reveal that at least three deodorants were 'radioactive consumer products' containing radionuclides of thorium (Th) series, uranium series, and potassium-40 that were added intentionally. Equivalent dose rates and effective dose rates were calculated using the activities in these deodorants. There were no samples breaking the nuclear reactor and fuel regulation law. Radioactive concentration of the deodorant for a shoe-shelf is higher than other deodorants, and the total concentrations of daughter nuclides of Th which are radioactive equilibrium with 224 Ra exceeded 90 Bq·g -1 . The effective dose rate at one meter from the shoe-shelf-deodorant is 8.6x10 -4 μSv·h -1 . Another type of shoe-deodorants is an insole that causes the surface dose of plantar skin. The equivalent dose was calculated as 1.9 μSv·h -1 at one millimeter from the insole. This study suggested that it needs to watch severely over the deodorants because many kinds of deodorants are used in home and some deodorants are radioactive consumer products. (author)

  8. The effect of habitual and experimental antiperspirant and deodorant product use on the armpit microbiome

    Directory of Open Access Journals (Sweden)

    Julie Urban

    2016-02-01

    Full Text Available An ever expanding body of research investigates the human microbiome in general and the skin microbiome in particular. Microbiomes vary greatly from individual to individual. Understanding the factors that account for this variation, however, has proven challenging, with many studies able to account statistically for just a small proportion of the inter-individual variation in the abundance, species richness or composition of bacteria. The human armpit has long been noted to host a high biomass bacterial community, and recent studies have highlighted substantial inter-individual variation in armpit bacteria, even relative to variation among individuals for other body habitats. One obvious potential explanation for this variation has to do with the use of personal hygiene products, particularly deodorants and antiperspirants. Here we experimentally manipulate product use to examine the abundance, species richness, and composition of bacterial communities that recolonize the armpits of people with different product use habits. In doing so, we find that when deodorant and antiperspirant use were stopped, culturable bacterial density increased and approached that found on individuals who regularly do not use any product. In addition, when antiperspirants were subsequently applied, bacterial density dramatically declined. These culture-based results are in line with sequence-based comparisons of the effects of long-term product use on bacterial species richness and composition. Sequence-based analyses suggested that individuals who habitually use antiperspirant tended to have a greater richness of bacterial OTUs in their armpits than those who use deodorant. In addition, individuals who used antiperspirants or deodorants long-term, but who stopped using product for two or more days as part of this study, had armpit communities dominated by Staphylococcaceae, whereas those of individuals in our study who habitually used no products were dominated by

  9. Physicochemical and sensory characterization of refined and deodorized tuna (Thunnus albacares) by-product oil obtained by enzymatic hydrolysis.

    Science.gov (United States)

    de Oliveira, Dayse A S B; Minozzo, Marcelo G; Licodiedoff, Silvana; Waszczynskyj, Nina

    2016-09-15

    In this study, the effects of chemical refining and deodorization on fatty acid profiles and physicochemical and sensory characteristics of the tuna by-product oil obtained by enzymatic hydrolysis were evaluated. Enzymatic extraction was conducted for 120 min at 60 °C and pH 6.5 using Alcalase at an enzyme-substrate ratio of 1:200 w/w. The chemical refining of crude oil consisted of degumming, neutralization, washing, drying, bleaching, and deodorization; deodorization was conducted at different temperatures and processing times. Although chemical refining was successful, temperature and chemical reagents favored the removal of polyunsaturated fatty acids (PUFA) from the oil. Aroma attributes of fishy odor, frying odor, and rancid odor predominantly contributed to the sensory evaluation of the product. Deodorization conditions of 160 °C for 1h and 200 °C for 1h were recommended for the tuna by-product oil, which is rich in PUFA. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Production of natural antioxidants from vegetable oil deodorizer distillates: effect of catalytic hydrogenation.

    Science.gov (United States)

    Pagani, María Ayelén; Baltanás, Miguel A

    2010-02-01

    Natural tocopherols are one of the main types of antioxidants found in living creatures, but they also have other critical biological functions. The biopotency of natural (+)-alpha-tocopherol (RRR) is 36% higher than that of the synthetic racemic mixture and 300% higher than the SRR stereoisomer. Vegetable oil deodorizer distillates (DD) are an excellent source of natural tocopherols. Catalytic hydrogenation of DD preconcentrates has been suggested as a feasible route for recovery of tocopherols in high yield. However, it is important to know whether the hydrogenation operation, as applied to these tocopherol-rich mixtures, is capable of preserving the chiral (RRR) character, which is critical to its biopotency. Fortified (i.e., (+)-alpha-tocopherol enriched) sunflower oil and methyl stearate, as well as sunflower oil DD, were fully hydrogenated using commercial Ni and Pd catalysts (120-180 degrees C; 20-60 psig). Products were analyzed by chiral HPLC. Results show that the desired chiral configuration (RRR) is fully retained. Thus, the hydrogenation route can be safely considered as a valid alternative for increasing the efficiency of tocopherol recovery processes from DDs while preserving their natural characteristics.

  11. Fragrances and other materials in deodorants

    DEFF Research Database (Denmark)

    Rastogi, S C; Lepoittevin, J P; Johansen, Jeanne Duus

    1998-01-01

    Deodorants are one of the most frequently-used types of cosmetics and are a source of allergic contact dermatitis. Therefore, a gas chromatography - mass spectrometric analysis of 71 deodorants was performed for identification of fragrance and non-fragrance materials present in marketed deodorants...... to formulate cosmetic products (over 3500), 226 chemicals were identified in a sample of 71 deodorants. 84 molecules were found to contain at least 1 structural alert, and 70 to belong to, or be susceptible to being metabolized into, the chemical group of aldehydes, ketones and alpha,beta-unsaturated aldehydes......, ketone or esters. The combination of GC-MS and SARs analysis could be helpful in the selection of substances for supplementary investigations regarding sensitizing properties. Thus, it may be a valuable tool in the management of contact allergy to deodorants and for producing new deodorants...

  12. Deodorizing petroleum oils, etc

    Energy Technology Data Exchange (ETDEWEB)

    Haller, A

    1906-06-14

    A process of purifying and deodorizing petroleum oils, gasolines, ethers, benzines, shale oils, resins, and similar products, consisting essentially in passing the vapors of the liquids with a current of hydrogen or of gases high in hydrogen over divided metals, such as nickel, copper, cobalt, iron, platinum, etc., heated to a temperature between 100/sup 0/C and 350/sup 0/C, the vapors passing before entering the apparatus through a column of copper heated to above 350/sup 0/C.

  13. Biodiesel production from soybean oil deodorizer distillate usingcalcined duck eggshell as catalyst

    International Nuclear Information System (INIS)

    Yin, Xiulian; Duan, Xiuli; You, Qinghong; Dai, Chunhua; Tan, Zhongbiao; Zhu, Xiaoyan

    2016-01-01

    Highlights: • Calcined DES was used as catalyst for biodiesel production from SODD. • The obtained CaO was characterized by XRD, FT-IR, SEM and the optimal calcination temperature was 900 °C. • The biodiesel yield was 94.6% at the optimal transesterification conditions. • The biodiesel yield was above 80% after five times usage. - Abstract: Biodiesel production from soybean oil deodorizer distillate (SODD) using calcined duck eggshell (DES) as catalyst was studied. An inexpensive and environment-friendly catalyst was prepared from waste DES which is a source of calcium carbonate. The calcium carbonate could be changed to calcium oxide (CaO) under high temperatures. The obtained CaO was characterized by X-ray diffraction (XRD), Fourier Transmission Infrared Spectra (FT-IR), Scanning Electron Microscopy (SEM). XRF was used to determine the elemental composition of the catalyst. BET analysis was performed to determine specific surface area, pore volume and particle size of the catalysts. Results showed that at 800 °C and 900 °C the calcium carbonate in DES was changed to CaO. The pre-esterification of SODD was conducted under the following conditions: H_2SO_4 concentration (v/w, based on oil weight) 1.5%, methanol to oil molar ratio 12:1, reaction time 120 min and reaction temperature 60 °C. Thephytosterols were removed by cooling down step by stepand temperature steps were 15 °C, 5 °C, −5 °C. The process of biodiesel production from pre-esterified SODD using the obtained CaO as catalyst was studied and the optimal conditions were: calcination temperature of 900 °C, catalyst amount of 10 wt.%, methanol to oil ratio of 10:1, reaction temperature of 60 °C and reaction time of 80 min and the biodiesel yield was 94.6% at these conditions. The reusability of the DES-derived catalyst was tested and the results showed that the biodiesel yield was above 80% after five times usage and was lower than 60% after 8 times usage.

  14. Deodorants on the European market

    DEFF Research Database (Denmark)

    Rastogi, Suresh Chandra; Johansen, J D; Frosch, Peter J

    1998-01-01

    allergens from the fragrance mix and 14 other commonly used fragrance materials. The deodorants were purchased at retail outlets in 5 European countries. It was found that in general, fragrance mix ingredients were more frequently present in vapo- and aerosol sprays than in roll-on products. The levels...... of the fragrance mix substances ranged from 0.0001-0.2355%. The products investigated contained cinnamic aldehyde and isoeugenol less frequently (17% and 29% respectively), and eugenol and geraniol most frequently (57% and 76% respectively). The 14 other fragrance materials were found in 40-97% of the deodorants...... could be drawn about the other fragrance mix constituents, as threshold levels in sensitized individuals have not been investigated. Furthermore, all of the fragrance materials investigated were frequently found in deodorants and, apart from the fragrance mix ingredients, the extent of problems...

  15. Deodorant ceramic catalyst. Dasshu ceramics shokubai

    Energy Technology Data Exchange (ETDEWEB)

    Arai, K. (Kobe Steel Ltd., Kobe (Japan)); Naka, R. (Hitachi Ltd., Tokyo (Japan))

    1993-07-01

    Concerning debromination to be used for the filter of deodorizing device, those of long life and high deodorizing performance are demanded a great deal. As one of this kind of debromination, a deodorant ceramic catalyst (mangantid) has been developed and put for practical use as deodorant for refrigerator. In this article, the information and knowledge obtained by the development of mangantid, the features as well as several properties of the product are stated. The deodorizing methods currently used practically are roughly divided into 6 kinds such as the adsorption method, the direct combustion method, the catalytic method and the oxidation method, but each of them has its own merit and demerit, hence it is necessary to select the method in accordance with the kind of odor and its generating condition. Mangantid is a compound body of high deodorant material in a honeycomb configuration, and has the features that in comparison with the existing deordorants, its pressure loss is smaller, its deodorizing rate is bigger, and acidic, neutral and basic gaseous components can be removed in a well-balanced manner. Deodorization with mangantid has the mechanism to let the odorous component contact and react with the catalyst and change the component to the non-odorous component in the temperature range from room temperature to the low temperature region. 5 refs., 11 figs., 1 tab.

  16. Deodorant poisoning

    Science.gov (United States)

    ... Poisoning and Drug Overdose . 4th ed. Philadelphia, PA: Elsevier Saunders; 2007:chap 100. Farmer B, Seger DL. ... Textbook of Critical Care . 7th ed. Philadelphia, PA: Elsevier; 2017:chap 153. Meehan TJ. Approach to the ...

  17. Do deodorants/underarm cosmetics cause cancer?

    Directory of Open Access Journals (Sweden)

    Serap Öztürkcan

    2016-09-01

    Full Text Available The effect of deodorant use on breast cancer development has generated considerable interest in both the scientific community and the mainstream media. Primary observational studies and numerous reviews investigating the effect of regular deodorant use on breast cancer development have been undertaken. There is no consensus in this regard. Some epidemiological studies have attempted to directly address the issue of underarm cosmetic use and breast cancer. On the other hand, many studies found no association between antiperspirant use and the risk of breast cancer. There is no difference in the current use of antiperspirant/deodorant products between breast cancer patients and nonaffected matched controls. There is no scientific evidence or research data that ingredients in underarm antiperspirants or deodorants cause cancer.

  18. Deodorants: An experimental provocation study with cinnamic aldehyde

    DEFF Research Database (Denmark)

    Bruze, M.; Johansen, J. D.; Andersen, K. E.

    2003-01-01

    BACKGROUND: Axillary dermatitis is common and overrepresented in individuals with contact allergy to fragrances. Many individuals suspect their deodorants to be the incriminating products. OBJECTIVE: Our aim was to investigate the significance of cinnamic aldehyde in deodorants for the development...... of axillary dermatitis when used by individuals with and without contact allergy to cinnamic aldehyde. METHODS: Patch tests with deodorants and ethanol solutions with cinnamic aldehyde, and repeated open application tests with roll-on deodorants without and with cinnamic aldehyde at different concentrations......, were performed in 37 patients with dermatitis, 20 without and 17 with contact allergy to cinnamic aldehyde. RESULTS: A repeated open application test with positive findings was noted only in patients hypersensitive to cinnamic aldehyde (P deodorants containing...

  19. Deodorant effects of a sage extract stick: Antibacterial activity and sensory evaluation of axillary deodorancy

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Shahtalebi

    2013-01-01

    Full Text Available Background: Deodorant products prevent the growth and activity of the degrading apocrine gland bacteria living in the armpit. Common antibacterial agents in the market like triclosan and aluminum salts, in spite of their suitable antibacterial effects, increase the risk of Alzheimer′s disease, breast and prostate cancers or induce contact dermatitis. Therefore, plant extracts possessing antibacterial effects are of interest. The aim of the present study was to verify the in vitro antimicrobial effects of different sage extracts against two major bacteria responsible for axillary odor, and to evaluate the deodorant effect of a silicon-based stick containing sage extracts in different densities in humans. Materials and Methods: Different fractions of methanolic extract of Salvia officinalis (sage were evaluated on a culture of armpit skin surface of volunteers through agar microdilution antimicrobial assay. Then, randomized, double-blind placebo-controlled clinical trial with the best antibacterial fraction was conducted on 45 female healthy volunteers. Participants were treated with a single dose in four groups, each containing 15 individuals: Group 1 (200 μg/mL, 2 (400 μg/mL, 3 (600 μg/mL of dichloromethane sage extract, and placebo (without extract. A standard sensory evaluation method for the evaluation of deodorant efficacy was used before, and two hours, four hours, and eight hours after single application of a deodorant or placebo (ASTM method E 1207-87 Standard Practice for the Sensory Evaluation of Axillary Deodorancy. Results: The data were analyzed with two factors relating to densities and time. In 45 participants with a mean [± standard deviation (SD] age of 61.5±11.8 years, statistically significant within-group differences were observed before and two, four, and eight hours after deodorant treatment for groups 1, 2, and 3. Groups 1, 2, and 3 had a significantly smaller odor score than placebo after two, four, and eight hours

  20. Fragrances and other materials in deodorants

    DEFF Research Database (Denmark)

    Rastogi, Suresh Chandra; Lepoittevin, J P; Johansen, J D

    1998-01-01

    Deodorants are one of the most frequently-used types of cosmetics and are a source of allergic contact dermatitis. Therefore, a gas chromatography - mass spectrometric analysis of 71 deodorants was performed for identification of fragrance and non-fragrance materials present in marketed deodorant...

  1. Deodorant effects of a sage extract stick: Antibacterial activity and sensory evaluation of axillary deodorancy.

    Science.gov (United States)

    Shahtalebi, Mohammad Ali; Ghanadian, Mustafa; Farzan, Ali; Shiri, Niloufar; Shokri, Dariush; Fatemi, Syed Ali

    2013-10-01

    Deodorant products prevent the growth and activity of the degrading apocrine gland bacteria living in the armpit. Common antibacterial agents in the market like triclosan and aluminum salts, in spite of their suitable antibacterial effects, increase the risk of Alzheimer's disease, breast and prostate cancers or induce contact dermatitis. Therefore, plant extracts possessing antibacterial effects are of interest. The aim of the present study was to verify the in vitro antimicrobial effects of different sage extracts against two major bacteria responsible for axillary odor, and to evaluate the deodorant effect of a silicon-based stick containing sage extracts in different densities in humans. Different fractions of methanolic extract of Salvia officinalis (sage) were evaluated on a culture of armpit skin surface of volunteers through agar microdilution antimicrobial assay. Then, randomized, double-blind placebo-controlled clinical trial with the best antibacterial fraction was conducted on 45 female healthy volunteers. Participants were treated with a single dose in four groups, each containing 15 individuals: Group 1 (200 μg/mL), 2 (400 μg/mL), 3 (600 μg/mL) of dichloromethane sage extract, and placebo (without extract). A standard sensory evaluation method for the evaluation of deodorant efficacy was used before, and two hours, four hours, and eight hours after single application of a deodorant or placebo (ASTM method E 1207-87 Standard Practice for the Sensory Evaluation of Axillary Deodorancy). The data were analyzed with two factors relating to densities and time. In 45 participants with a mean [± standard deviation (SD)] age of 61.5±11.8 years, statistically significant within-group differences were observed before and two, four, and eight hours after deodorant treatment for groups 1, 2, and 3. Groups 1, 2, and 3 had a significantly smaller odor score than placebo after two, four, and eight hours (P sage extract sticks (P sage extract of 200, 400, or 600

  2. Drugs@FDA: FDA Approved Drug Products

    Science.gov (United States)

    ... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

  3. Tocopherol composition of deodorization distillates and their antioxidative activity.

    Science.gov (United States)

    Nogala-Kalucka, Malgorzata; Korczak, Jozef; Wagner, Karl-Heinz; Elmadfa, Ibrahim

    2004-02-01

    During the last stage of plant oil refining, deodorization distillates containing very important biological substances such as tocopherols, sterols, terpenoids or hydrocarbons are formed as a by-products. This study aimed at evaluating the content and antioxidant capacity of tocopherol concentrates from deodorization distillates obtained after the refining of rapeseed, soybean and sunflower oil. The majority of the matrix substances were eliminated from deodorization distillates by freezing with an acetone solution at -70 degrees C. The tocopherol concentrates obtained in this way contained approximately fivefold more tocopherols than the quantity in condensates after deodorization. Antioxidant activity was investigated by observing the peroxide value at 25 degrees C and using the Oxidograph test. The test medium was lard enriched with the tocopherol concentrates of the three plant oils versus single, synthetic alpha-, gamma- and delta-tocopherols (-T), which served for comparison. In these model systems, all investigated tocopherol concentrates exhibited antioxidant capacity. Their antioxidant effect was significantly lower than that of single delta-T and gamma-T, but significantly higher than alpha-T. The results prove that natural tocopherol concentrates obtained from plant oils are valuable food antioxidants and they also increase the biological and nutritional value of food especially when administered to animal fats or food of animal origin. Tocopherol concentrates can fully replace synthetic antioxidants that have been used thus far.

  4. Radiopacity of household deodorizers, air fresheners, and moth repellents.

    Science.gov (United States)

    Woolf, A D; Saperstein, A; Zawin, J; Cappock, R; Sue, Y J

    1993-01-01

    Household deodorizers and moth repellents are common agents implicated in many childhood poisonings. Their ingredients usually include either paradichlorobenzene or naphthalene compressed into a solid ball or another shape, sometimes with added essential oils and fragrances. Because medically naphthalene is a more important toxin than paradichlorobenzene, with hematologic and nervous system effects, clinicians often seek to discern which product has been ingested. We discovered fortuitously that a mothball swallowed by a retarded adult was radiopaque, and so designed an in vitro experiment to study the radiopacity of a variety of household deodorizers and products. Of 10 products screened for radiopacity by two radiologists, those containing paradichlorobenzene were consistently strongly radiopaque; those containing naphthalene were radiolucent. A third alternative ingredient which is used in some toilet bowl deodorizers, cetrimonium bromide, was also radiopaque. Radiopacity of paradichlorobenzene or cetrimonium bromide-containing products did not dissipate with time. We speculate that the halogen within the chemical structure of these compounds accounts for their radiopacity. We conclude that paradichlorobenzene-containing commercial products can be distinguished clinically from those containing naphthalene by the performance of an abdominal radiograph.

  5. Deodorants are the leading cause of allergic contact dermatitis to fragrance ingredients.

    Science.gov (United States)

    Heisterberg, Maria V; Menné, Torkil; Andersen, Klaus E; Avnstorp, Christian; Kristensen, Berit; Kristensen, Ove; Kaaber, Knud; Laurberg, Grete; Henrik Nielsen, Niels; Sommerlund, Mette; Thormann, Jens; Veien, Niels K; Vissing, Susanne; Johansen, Jeanne D

    2011-05-01

    Fragrances frequently cause contact allergy, and cosmetic products are the main causes of fragrance contact allergy. As the various products have distinctive forms of application and composition of ingredients, some product groups are potentially more likely to play a part in allergic reactions than others. To determine which cosmetic product groups cause fragrance allergy among Danish eczema patients. This was a retrospective study based on data collected by members of the Danish Contact Dermatitis Group. Participants (N = 17,716) were consecutively patch tested with fragrance markers from the European baseline series (2005-2009). Of the participants, 10.1% had fragrance allergy, of which 42.1% was caused by a cosmetic product: deodorants accounted for 25%, and scented lotions 24.4%. A sex difference was apparent, as deodorants were significantly more likely to be listed as the cause of fragrance allergy in men (odds ratio 2.2) than in women. Correlation was observed between deodorants listed as the cause of allergy and allergy detected with fragrance mix II (FM II) and hydroxyisohexyl 3-cyclohexene carboxaldehyde. Deodorants were the leading causes of fragrance allergy, especially among men. Seemingly, deodorants have an 'unhealthy' composition of the fragrance chemicals present in FM II. © 2011 John Wiley & Sons A/S.

  6. Deodorants on the European market: quantitative chemical analysis of 21 fragrances

    DEFF Research Database (Denmark)

    Rastogi, S C; Johansen, J D; Frosch, P

    1998-01-01

    allergens from the fragrance mix and 14 other commonly used fragrance materials. The deodorants were purchased at retail outlets in 5 European countries. It was found that in general, fragrance mix ingredients were more frequently present in vapo- and aerosol sprays than in roll-on products. The levels...... of the fragrance mix substances ranged from 0.0001-0.2355%. The products investigated contained cinnamic aldehyde and isoeugenol less frequently (17% and 29% respectively), and eugenol and geraniol most frequently (57% and 76% respectively). The 14 other fragrance materials were found in 40-97% of the deodorants...... could be drawn about the other fragrance mix constituents, as threshold levels in sensitized individuals have not been investigated. Furthermore, all of the fragrance materials investigated were frequently found in deodorants and, apart from the fragrance mix ingredients, the extent of problems...

  7. Drug product selection: legal issues.

    Science.gov (United States)

    Christensen, T P; Kirking, D M; Ascione, F J; Welage, L S; Gaither, C A

    2001-01-01

    To review the potential legal liability of the pharmacist in the drug product selection process. Published articles identified through MEDLINE, published law reviews identified through InfoTrac, and appellate court decisions. Search terms used included pharmacist liability, drug product selection, and generic substitution. Additional articles, books, and appellate court decisions were identified from the bibliographies of retrieved articles and citations in appellate court decisions. Pharmacists engaging in drug product selection are civilly liable under three legal theories: negligence, express or implied warranties, and strict product liability. Potential criminal liability includes prosecution for insurance fraud, deceptive business practices, and violation of state drug product selection laws and regulation. Pharmacists increase their liability when engaging in drug product selection, but the increase is small. Still, the law continues to evolve as pharmacists seek expanded roles and responsibilities. When courts give closer examination to pharmacists' expanded role, it is likely that pharmacists' liability will increase.

  8. 27 CFR 21.115 - Kerosene (deodorized).

    Science.gov (United States)

    2010-04-01

    ....115 Kerosene (deodorized). (a) Distillation range. No distillate should come over below 340 °F. and none above 570 °F. (b) Flash point. 155 °F. minimum. [T.D. ATF-133, 48 FR 24673, June 2, 1983...

  9. Quantitative Determination of Aluminum in Deodorant Brands: A Guided Inquiry Learning Experience in Quantitative Analysis Laboratory

    Science.gov (United States)

    Sedwick, Victoria; Leal, Anne; Turner, Dea; Kanu, A. Bakarr

    2018-01-01

    The monitoring of metals in commercial products is essential for protecting public health against the hazards of metal toxicity. This article presents a guided inquiry (GI) experimental lab approach in a quantitative analysis lab class that enabled students' to determine the levels of aluminum in deodorant brands. The utility of a GI experimental…

  10. Experimental elicitation with hydroxyisohexyl-3-cyclohexene carboxaldehyde-containing deodorants.

    Science.gov (United States)

    Jørgensen, Pia Haslund; Jensen, Charlotte Devantier; Rastogi, Suresh; Andersen, Klaus Ejner; Johansen, Jeanne Duus

    2007-03-01

    Hydroxyisohexyl-3-cyclohexene carboxaldehyde (HICC) known as Lyral is a frequent allergen. It is used in more than 50% of marketed deodorants. The aim of the present study was to determine elicitation thresholds for HICC under simulated conditions of deodorant use. 15 patients with previously diagnosed contact allergy to HICC were patch tested with 5 solutions of HICC-scented and HICC-unscented deodorants. Patients and 10 healthy controls performed a use test in the axillae using deodorants scented with HICC in increasing concentrations and unscented deodorants as control. The concentration of HICC was increased every second week (200, 600, and 1800 p.p.m.) until either a reaction developed or for 6 weeks. 14 patients completed the study, and all developed unilateral eczema from the HICC-containing deodorant, while controls were all negative (P= 0.004). In 9/14 patients, a positive use test developed during the first 2 weeks to the deodorant containing 200 p.p.m. HICC. Positive correlations were found between the day of positive use and patch test threshold concentration of the HICC solutions (r= 0.71, P= 0.01) as well as the patch test thresholds of the HICC-scented deodorants (r= 0.74, P= 0.007). In conclusion, HICC elicits allergic contact dermatitis in a high proportion of sensitized individuals at common usage concentrations in deodorants.

  11. [Microbiological and physicochemical evaluation of pasteurized beverages fortified with orange deodorized residues extracts].

    Science.gov (United States)

    Moreno Alvarez, Mario José; Machado, Alexandra; Padrón, Arelis; García, David; Belén Camacho, Douglas Rafael

    2004-09-01

    Microbiological and physicochemical parameters of pasteurized beverages conditioned with aqueous extracts from orange deodorized residues were evaluated. The fruits used were selected according to following criterion: homogenous maturity, without physical damage and absence of apparent chlorophyll. Orange peels were dried and transformed to flour. The juice was evaluated by means of these parameters: pH 3.90, degrees Brix 10, titrable acidity 0.33 g of citric acid/100 mL and total carotenoids 0.0078 mg/mL. Volatil compounds of the flour that may to cause bitterness were separated by means of two methods of deodorization: distillation in current of vapor and in autoclave to 121 degrees C; then, the flour was extracted with water (relation 1:50 p/v). Pasteurized citric beverages (orange juice) were elaborated adding the deodorized extracts. pH, degrees Brix, titrable acidity and total carotenoids showed no significant differences (P>0.05). Microbiological results were according to pasteurized products. Sensorial analysis by untrained panel showed no signiificant differences. In conclusion, the deodorant processes were effectives and permitted the inclusion of aquasoluble compounds as flavonoids with antioxidant activity.

  12. Optimizing clinical drug product performance

    DEFF Research Database (Denmark)

    Dickinson, Paul A.; Kesisoglou, Filippos; Flanagan, Talia

    2016-01-01

    The aim of Biopharmaceutics Risk Assessment Roadmap (BioRAM) and the BioRAM Scoring Grid is to facilitate optimization of clinical performance of drug products. BioRAM strategy relies on therapy-driven drug delivery and follows an integrated systems approach for formulating and addressing critical...... questions and decision-making (J Pharm Sci. 2014,103(11): 3777-97). In BioRAM, risk is defined as not achieving the intended in vivo drug product performance, and success is assessed by time to decision-making and action. Emphasis on time to decision-making and time to action highlights the value of well....... Application of the BioRAM Scoring Grid is illustrated using published literature. Organizational considerations for implementing BioRAM strategy, including the interactions, function, and skillsets of the BioRAM group members, are also reviewed. As a creative and innovative systems approach, we believe...

  13. Experimental elicitation with hydroxyisohexyl-3-cyclohexene carboxaldehyde-containing deodorants

    DEFF Research Database (Denmark)

    Jørgensen, Pia Haslund; Jensen, Charlotte Devantier; Rastogi, Suresh

    2007-01-01

    Hydroxyisohexyl-3-cyclohexene carboxaldehyde (HICC) known as Lyral is a frequent allergen. It is used in more than 50% of marketed deodorants. The aim of the present study was to determine elicitation thresholds for HICC under simulated conditions of deodorant use. 15 patients with previously...

  14. Deodorization of lipase-interesterified butterfat and rapeseed oil blends in a pilot deodorizer

    DEFF Research Database (Denmark)

    Rønne, Torben Harald; Jacobsen, Charlotte; Xu, Xuebing

    2006-01-01

    by free fatty acid (FFA) content, peroxide value (PV), volatiles, and the sensory evaluation of the samples with respect to flavor and odor (most importantly the butter flavor and odor and the off-flavor and odor from butyric acid). ANOVA partial least squares regression analysis showed that deodorization...

  15. Deodorization optimization of Camelina sativa oil: Oxidative and sensory studies

    DEFF Research Database (Denmark)

    Hrastar, Robert; Cheong, Ling‐Zhi; Xu, Xuebing

    2011-01-01

    [peroxide value (PV), p‐anisidine value (p‐AV), γ‐tocopherol (γ‐T) and oxidative stability (OS)]. Additionally, sensory evaluation was performed. RSM analysis showed a significant effect of deodorization temperature and to a lesser extent, deodorization steam flow and time on removal of oxidative compounds....... In the present study RSM and principal component analysis (PCA) were used to optimize bench‐scale deodorization of CO. Mathematical models were generated through multiple regressions with backward elimination, describing the effects of process parameters (temperature, steam flow, time) on oil quality indicators......, flavour and odour. PCA of chemical and sensory results showed that deodorization temperature affected the sensory properties in the samples. The best conditions for removing undesirable flavour and odour were achieved by using a deodorization temperature of 195–210°C....

  16. Simulation of thin-film deodorizers in palm oil refining

    DEFF Research Database (Denmark)

    Ceriani, Roberta; Meirelles, Antonio J.A.; Gani, Rafiqul

    2010-01-01

    As the need for healthier fats and oils (natural vitamin and trans fat contents) and interest in biofuels are growing, many changes in the world's vegetable oil market are driving the oil industry to developing new technologies and recycling traditional ones. Computational simulation is widely used...... in the chemical and petrochemical industries as a tool for optimization and design of (new) processes, but that is not the case for the edible oil industry. Thin-film deodorizers are novel equipment developed for steam deacidification of vegetable oils, and no work on the simulation of this type of equipment...... could be found in the open literature. This paper tries to fill this gap by presenting results from the study of the effect of processing variables, such as temperature, pressure and percentage of stripping steam, in the final quality of product (deacidified palm oil) in terms of final oil acidity...

  17. Odors and deodorization in environment

    Energy Technology Data Exchange (ETDEWEB)

    Martin, G; Laffort, P

    1991-01-01

    This synthesis on olfaction studies is treating of sense of smell, smelling and stinking products, both on biology level and physico-chemical level. Reliable measuring methods were developed. Efficient treatments means were brought into operation. Gradually, legislation adjusts to these new nuisances.

  18. Electronic Animal Drug Product Listing Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Electronic Animal Drug Product Listing Directory is a directory of all animal drug products that have been listed electronically since June 1, 2009, to comply...

  19. Photostability and Photostabilization of Drugs and Drug Products

    OpenAIRE

    Ahmad, Iqbal; Ahmed, Sofia; Anwar, Zubair; Sheraz, Muhammad Ali; Sikorski, Marek

    2016-01-01

    Photostability studies of drugs and drug products are an integral part of the product development process in the pharmaceutical industry. These studies are carried out to ensure quality, efficacy, and safety of the formulated products during manufacture, storage, and use. This review deals with the concept of photostability and related aspects and the literature available in the field. It highlights the role of the photochemistry in the photostability studies, describes the functional groups ...

  20. 21 CFR 884.5425 - Scented or scented deodorized menstrual pad.

    Science.gov (United States)

    2010-04-01

    ...) added for aesthetic purposes (scented menstrual pad) or for deodorizing purposes (scented deodorized...) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter...

  1. Photostability and Photostabilization of Drugs and Drug Products

    Directory of Open Access Journals (Sweden)

    Iqbal Ahmad

    2016-01-01

    Full Text Available Photostability studies of drugs and drug products are an integral part of the product development process in the pharmaceutical industry. These studies are carried out to ensure quality, efficacy, and safety of the formulated products during manufacture, storage, and use. This review deals with the concept of photostability and related aspects and the literature available in the field. It highlights the role of the photochemistry in the photostability studies, describes the functional groups important for the photoreactivity of drugs, explains photophysical processes, and deals with the kinetics of photochemical reactions. The various modes of photodegradation of drugs with examples of selected compounds are presented. The biological consequences of the effect of light on the drug degradation are described. The photostability testing of drugs and drug products and the requirements under ICH guideline are discussed. Some information on the packaging requirements for the formulated products is provided. The various methods used for the photostabilization of solid and liquid dosage forms are also discussed.

  2. Development Considerations for Nanocrystal Drug Products.

    Science.gov (United States)

    Chen, Mei-Ling; John, Mathew; Lee, Sau L; Tyner, Katherine M

    2017-05-01

    Nanocrystal technology has emerged as a valuable tool for facilitating the delivery of poorly water-soluble active pharmaceutical ingredients (APIs) and enhancing API bioavailability. To date, the US Food and Drug Administration (FDA) has received over 80 applications for drug products containing nanocrystals. These products can be delivered by different routes of administration and are used in a variety of therapeutic areas. To aid in identifying key developmental considerations for these products, a retrospective analysis was performed on the submissions received by the FDA to date. Over 60% of the submissions were for the oral route of administration. Based on the Biopharmaceutics Classification System (BCS), most nanocrystal drugs submitted to the FDA are class II compounds that possess low aqueous solubility and high intestinal permeability. Impact of food on drug bioavailability was reduced for most nanocrystal formulations as compared with their micronized counterparts. For all routes of administration, dose proportionality was observed for some, but not all, nanocrystal products. Particular emphasis in the development of nanocrystal products was placed on the in-process tests and controls at critical manufacturing steps (such as milling process), mitigation and control of process-related impurities, and the stability of APIs or polymorphic form (s) during manufacturing and upon storage. This emphasis resulted in identifying challenges to the development of these products including accurate determination of particle size (distribution) of drug substance and/or nanocrystal colloidal dispersion, identification of polymorphic form (s), and establishment of drug substance/product specifications.

  3. Purification and deodorization of structured lipids by short path distillation

    DEFF Research Database (Denmark)

    Xu, Xuebing; Jacobsen, Charlotte; Nielsen, Nina Skall

    2002-01-01

    Purification of structured lipids (SL), produced from lipase- catalyzed acidolysis of rapeseed oil and capric acid, and deodorization of randomized SL, produced from chemical randomization of fish oil and tricaprin, were studied in a bench-scale short path distillation (SPD). SL obtained from...

  4. antibacterial activities of different brands of deodorants marketed

    African Journals Online (AJOL)

    boaz

    sweating by affecting sweat glands. Antiperspirants are typically applied to the underarms, while deodorants may also be applied on the feet and other areas in the form of body sprays2. Human perspiration is largely odourless until it is fermented by bacteria that thrives in hot, humid environments3. The human underarm is ...

  5. Inactive ingredient Search for Approved Drug Products

    Data.gov (United States)

    U.S. Department of Health & Human Services — According to 21 CFR 210.3(b)(8), an inactive ingredient is any component of a drug product other than the active ingredient. Only inactive ingredients in the final...

  6. 21 CFR 333.350 - Labeling of acne drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of acne drug products. 333.350 Section... Acne Drug Products § 333.350 Labeling of acne drug products. (a) Statement of identity. The labeling of the product contains the established name of the drug, if any, and identifies the product as an “acne...

  7. Examining the production costs of antiretroviral drugs.

    Science.gov (United States)

    Pinheiro, Eloan; Vasan, Ashwin; Kim, Jim Yong; Lee, Evan; Guimier, Jean Marc; Perriens, Joseph

    2006-08-22

    To present direct manufacturing costs and price calculations of individual antiretroviral drugs, enabling those responsible for their procurement to have a better understanding of the cost structure of their production, and to indicate the prices at which these antiretroviral drugs could be offered in developing country markets. Direct manufacturing costs and factory prices for selected first and second-line antiretroviral drugs were calculated based on cost structure data from a state-owned company in Brazil. Prices for the active pharmaceutical ingredients (API) were taken from a recent survey by the World Health Organization (WHO). The calculated prices for antiretroviral drugs are compared with quoted prices offered by privately-owned, for-profit manufacturers. The API represents the largest component of direct manufacturing costs (55-99%), while other inputs, such as salaries, equipment costs, and scale of production, have a minimal impact. The calculated prices for most of the antiretroviral drugs studied fall within the lower quartile of the range of quoted prices in developing country markets. The exceptions are those drugs, primarily for second-line therapy, for which the API is either under patent, in short supply, or in limited use in developing countries (e.g. abacavir, lopinavir/ritonavir, nelfinavir, saquinavir). The availability of data on the cost of antiretroviral drug production and calculation of factory prices under a sustainable business model provide benchmarks that bulk purchasers of antiretroviral drugs could use to negotiate lower prices. While truly significant price decreases for antiretroviral drugs will depend largely on the future evolution of API prices, the present study demonstrates that for several antiretroviral drugs price reduction is currently possible. Whether or not these reductions materialize will depend on the magnitude of indirect cost and profit added by each supplier over the direct production costs. The ability to

  8. Using minced horseradish roots and peroxides for the deodorization of swine manure: a pilot scale study.

    Science.gov (United States)

    Govere, Ephraim M; Tonegawa, Masami; Bruns, Mary Ann; Wheeler, Eileen F; Kephart, Kenneth B; Voigt, Jean W; Dec, Jerzy

    2007-04-01

    Enzymes that have proven to be capable of removing toxic compounds from water and soil may also be useful in the deodorization of animal manures. Considering that pork production in the US is a $40-billion industry with over half a million workers, odor control to protect air quality in the neighboring communities must be considered an essential part of managing livestock facilities. This pilot scale (20-120 L) study tested the use of minced horseradish (Armoracia rusticana L.) roots (1:10 roots to swine slurry ratio), with calcium peroxide (CaO(2) at 34 mM) or hydrogen peroxide (H(2)O(2) at 68 mM), to deodorize swine slurry taken from a 40,000-gallon storage pit at the Pennsylvania State University's Swine Center. Horseradish is known to contain large amounts of peroxidase, an enzyme that, in the presence of peroxides, can polymerize phenolic odorants and thus reduce the malodor. Twelve compounds commonly associated with malodor (seven volatile fatty acids or VFAs, three phenolic compounds and two indolic compounds) were used as odor indicators. Their concentration in swine slurry before and after treatment was determined by gas chromatography (GC) to assess the deodorization effect. The pilot scale testing demonstrated a complete removal of phenolic odorants (with a detection limit of 0.5 mg L(-1)) from the swine slurry, which was consistent with our previous laboratory experiments using 30-mL swine slurry samples. Horseradish could be recycled (reused) five times while retaining significant reduction in the concentration of phenolic odorants. In view of these findings, inexpensive plant materials, such as horseradish, represent a promising tool for eliminating phenolic odorants from swine slurry.

  9. Identification of odor volatile compounds and deodorization of Paphia undulata enzymatic hydrolysate

    Science.gov (United States)

    Chen, Deke; Chen, Xin; Chen, Hua; Cai, Bingna; Wan, Peng; Zhu, Xiaolian; Sun, Han; Sun, Huili; Pan, Jianyu

    2016-12-01

    Unfavorable fishy odour is an inevitable problem in aquatic products. In the present study, headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS) analysis of volatiles from untreated samples and three deodorized samples (under the optimal conditions) of Paphia undulata enzymatic hydrolysate revealed that the compounds contributing to the distinctive odor were 1-octen-3-ol, n-hexanal, n-heptanal, 2,4-heptadienal, and 2,4-decadienal, whereas n-pentanal, n-octanal, n-octanol, benzaldehyde, 2-ethylfuran and 2-pentylfuran were the main contributors to the aromatic flavor. The deodorizing effects of activated carbon (AC) adsorption, yeast extract (YE) masking and tea polyphenol (TP) treatment on a P. undulata enzymatic hydrolysate were investigated using orthogonal experiments with sensory evaluation as the index. The following optimized deodorization conditions were obtained: AC adsorption (35 mg mL-1, 80°C, 40 min), YE masking (7 mg mL-1, 45°C, 30 min) and TP treatment (0.4 mg mL-1, 40°C, 50 min). AC adsorption effectively removed off-flavor volatile aldehydes and ketones. YE masking modified the odor profile by increasing the relative contents of aromatic compounds and decreasing the relative contents of aldehydes and ketones. The TP treatment was not effective in reducing the odor score, but it significantly reduced the relative content of aldehydes while increasing that of alkanes. It is also notable that TP effectively suppressed trimethylamine (TMA) formation in a P. undulate hydrolysate solution for a period of 72 h.

  10. 21 CFR 211.94 - Drug product containers and closures.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drug product containers and closures. 211.94 Section 211.94 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... and use that can cause deterioration or contamination of the drug product. (c) Drug product containers...

  11. Sensory evaluation of dry-fermented sausage containing ground deodorized yellow mustard.

    Science.gov (United States)

    Li, Shuliu; Aliani, Michel; Holley, Richard A

    2013-10-01

    Ground deodorized yellow mustard is used as a binder and meat protein substitute in cooked processed meat products. Recent studies have shown that it has the potential to be used in uncooked processed meat products because of its natural antimicrobial properties. In the present study, ground deodorized yellow mustard was added to uncooked dry-fermented sausage during manufacture at 1% to 4% (w/w) and analyzed for its effects on starter cultures, physico-chemical properties, and consumer acceptability. Mustard had a nondose-dependent inhibitory effect on the Staphylococcus starter culture, had no effect on water activity or instrumental texture, and tended to accelerate sausage pH reduction. At 3% and 4% mustard, consumer scores on all sensory attributes as well as overall acceptability were significantly lower. The appearance and color of 3% and 4% mustard-treated sausages were liked slightly, whereas flavor, texture, and overall acceptability scores were reduced. The control without mustard and 1% mustard-treated sausages had similar sensory properties and were the most acceptable, while 2% mustard-treated sausages were given "like moderately" and "like slightly" descriptors. Sensory results mean that at concentrations necessary for mandated regulatory control of Escherichia coli O157:H7 in dry sausages, mustard may have a negative effect on consumer acceptance. © 2013 Institute of Food Technologists®

  12. Regulatory considerations concerning IND radiopharmaceutical drug products

    International Nuclear Information System (INIS)

    Nissel, M.

    1985-01-01

    The Food and Drug Administration is charged by the Food, Drug, and Cosmetic Act, as presently amended, to assure that any drug introduced into interstate commerce is safe and effective for the purposes for which it is labeled. A radiopharmaceutical is, by definition, a new drug unless there is in effect an approved New Drug Application (NDA) for it. Before the data for the NDA are compiled, investigative studies have to be done. Before such studies can be performed in humans, an exemption from the Act is necessary. This exemption, technically the Claimed Exemption for an Investigational New Drug, is termed the IND. Both the scientific and the administrative requirements for an IND are discussed. For radiopharmaceutical drug products (RDP's), the radiation hazards, as well as the pharmacological ones, must be documented. Should the early studies demonstrate a potential for efficacy in a certain condition or disease state, an investigative protocol for an extended clinical trial is presented. The necessary requirements for Institutional Review Board (IRB) approval and consent forms are discussed. For certain research purposes, uniquely for radioactive drugs, an IND is not required for certain specific studies; the requirements for such a research study, conducted under the auspices of an approved radioactive drug research committee, are outlined

  13. 21 CFR 340.50 - Labeling of stimulant drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of stimulant drug products. 340.50 Section 340.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE STIMULANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 340.50...

  14. Drug Products in the Medicaid Drug Rebate Program

    Data.gov (United States)

    U.S. Department of Health & Human Services — Active drugs that have been reported by participating drug manufacturers under the Medicaid Drug Rebate Program. All drugs are identified by National Drug Code...

  15. Prescription Drugs, Over-the-Counter Drugs, Supplements and Herbal Products

    Science.gov (United States)

    ... at risk? Zika virus and pregnancy Folic acid Medicine safety and pregnancy Birth defects prevention Learn how ... the-counter drugs, supplements and herbal products Prescription drugs, over-the-counter drugs, supplements and herbal products ...

  16. Defining Patient Centric Pharmaceutical Drug Product Design.

    Science.gov (United States)

    Stegemann, Sven; Ternik, Robert L; Onder, Graziano; Khan, Mansoor A; van Riet-Nales, Diana A

    2016-09-01

    The term "patient centered," "patient centric," or "patient centricity" is increasingly used in the scientific literature in a wide variety of contexts. Generally, patient centric medicines are recognized as an essential contributor to healthy aging and the overall patient's quality of life and life expectancy. Besides the selection of the appropriate type of drug substance and strength for a particular indication in a particular patient, due attention must be paid that the pharmaceutical drug product design is also adequately addressing the particular patient's needs, i.e., assuring adequate patient adherence and the anticipate drug safety and effectiveness. Relevant pharmaceutical design aspects may e.g., involve the selection of the route of administration, the tablet size and shape, the ease of opening the package, the ability to read the user instruction, or the ability to follow the recommended (in-use) storage conditions. Currently, a harmonized definition on patient centric drug development/design has not yet been established. To stimulate scientific research and discussions and the consistent interpretation of test results, it is essential that such a definition is established. We have developed a first draft definition through various rounds of discussions within an interdisciplinary AAPS focus group of experts. This publication summarizes the outcomes and is intended to stimulate further discussions with all stakeholders towards a common definition of patient centric pharmaceutical drug product design that is useable across all disciplines involved.

  17. Patch test results with patients' own perfumes, deodorants and shaving lotions: results of the IVDK 1998-2002.

    Science.gov (United States)

    Uter, W; Geier, J; Schnuch, A; Frosch, P J

    2007-03-01

    Assessment of the value of patch testing patients' own perfumes, eau de toilette, deodorants and shaving lotions with regard to diagnosing contact allergy to fragrances, and an analysis of the spectrum of concurrent patch test reactions to single fragrance allergens. Data of the Information Network of Departments of Dermatology (IVDK; http://www.ivdk.org) regarding patch test results with above products brought in by the patient, considered as possible cause of contact dermatitis, were retrospectively analysed. Between 1998 and 2002, 1468 patients were patch tested with 2557 single products (deodorants, n = 1094; eau de toilette, n = 598; perfume, n = 530; and pre- or after-shave, n = 325; remainder not classifiable), mostly 'as is'. Positive reactions were observed in 129 patients (to 191 products). In 58 of these patients, no further patch test reactions to the fragrance mix (FM-I), Myroxylon pereirae resin (balsam of Peru) or 4-(4-hydroxy-4-methyl-pentyl)-3-cyclohexencarboxaldehyde (e.g. Lyral(R)) were found. A strong association between contact sensitivity to the above commercial allergens and positive reactions to products was observed. Some single compounds such as ylang-ylang oil, propolis and especially oak moss absolute are important allergens in the 'perfume-positive' subgroup, but less in a subgroup positive to own deodorants. Patch testing this scope of products, brought in by the patient, can be regarded as a simple, safe and effective method to diagnose clinically relevant contact sensitization - the more so, as the composition of such products is ever-changing, and the sensitivity of established 'screening allergens' is thus insufficient.

  18. Camelina sativa Oil Deodorization: Balance Between Free Fatty Acids and Color Reduction and Isomerized Byproducts Formation

    DEFF Research Database (Denmark)

    Hrastar, Robert; Cheong, Ling-Zhi; Xu, Xuebing

    2011-01-01

    parameters for bench-scale deodorization of camelina oil. The mathematical models generated described the effects of process parameters (temperature, steam flow, time) on several deodorization quality indicators: free fatty acids (FFA), trans fatty acids (TFA), color, and polymerized triglycerides (PTG...

  19. Preparation of Biodiesel with Liquid Synergetic Lipases from Rapeseed Oil Deodorizer Distillate.

    Science.gov (United States)

    Zeng, Leping; He, Yaojia; Jiao, Liangcheng; Li, Kai; Yan, Yunjun

    2017-11-01

    To reduce industrial production cost, cheap and easily available rapeseed oil deodorizer distillates were used as feedstock to prepare biodiesel in this study. As a result, liquid forms of Candida rugosa lipase and Rhizopus oryzae lipase (ROL) were functioned as new and effective catalysts with biodiesel yield of 92.63% for 30 h and 94.36% for 9 h, respectively. Furthermore, the synergetic effect between the two lipases was employed to enhance biodiesel yield with a result of 98.16% in 6 h under optimized conditions via response surface methodology. The obtained conversion rate surpassed both yields of the individual two lipases and markedly shortened the reaction time. The resultant optimal conditions were ROL ratio 0.84, water content 46 wt% (w/w), reaction temperature 34 °C, and reaction time 6 h.

  20. Approved Drug Products with Therapuetic Equivalence Evaluations (Orange Book)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The publication Approved Drug Products with Therapeutic Equivalence Evaluations (the List, commonly known as the Orange Book) identifies drug products approved on...

  1. Plant natural products research in tuberculosis drug discovery and ...

    African Journals Online (AJOL)

    Plant natural products research in tuberculosis drug discovery and development: A situation report ... African Journal of Biotechnology ... tuberculosis (XDR-TB), call for the development of new anti-tuberculosis drugs to combat this disease.

  2. 75 FR 73108 - Guidance for Industry on Abbreviated New Drug Applications: Impurities in Drug Products...

    Science.gov (United States)

    2010-11-29

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0584... Products.'' This guidance updates recommendations regarding degradation products and updates the draft... information on listing of degradation products, setting acceptance criteria, and qualifying degradation...

  3. Dependence of deodorant usage on ABCC11 genotype: scope for personalized genetics in personal hygiene.

    Science.gov (United States)

    Rodriguez, Santiago; Steer, Colin D; Farrow, Alexandra; Golding, Jean; Day, Ian N M

    2013-07-01

    Earwax type and axillary odor are genetically determined by rs17822931, a single-nucleotide polymorphism (SNP) located in the ABCC11 gene. The literature has been concerned with the Mendelian trait of earwax, although axillary odor is also Mendelian. Ethnic diversity in rs17822931 exists, with higher frequency of allele A in east Asians. Influence on deodorant usage has not been investigated. In this work, we present a detailed analysis of the rs17822931 effect on deodorant usage in a large (N∼17,000 individuals) population cohort (the Avon Longitudinal Study of Parents and Children (ALSPAC)). We found strong evidence (P=3.7 × 10(-20)) indicating differential deodorant usage according to the rs17822931 genotype. AA homozygotes were almost 5-fold overrepresented in categories of never using deodorant or using it infrequently. However, 77.8% of white European genotypically nonodorous individuals still used deodorant, and 4.7% genotypically odorous individuals did not. We provide evidence of a behavioral effect associated with rs17822931. This effect has a biological basis that can result in a change in the family's environment if an aerosol deodorant is used. It also indicates potential cost saving to the nonodorous and scope for personalized genetics usage in personal hygiene choices, with consequent reduction of inappropriate chemical exposures for some.

  4. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The...

  5. [Impact of air fresheners and deodorizers on the indoor total volatile organic compounds].

    Science.gov (United States)

    Jinno, Hideto; Tanaka-Kagawa, Toshiko; Obama, Tomoko; Miyagawa, Makoto; Yoshikawa, Jun; Komatsu, Kazuhiro; Tokunaga, Hiroshi

    2007-01-01

    Indoor air quality is a growing health concern because of the increased incidence of the building-related illness, such as sick-building syndrome and multiple chemical sensitivity/idiopathic environmental intolerance. In order to effectively reduce the unnecessary chemical exposure in the indoor environment, it would be important to quantitatively compare the emissions from many types of sources. Besides the chemical emissions from the building materials, daily use of household products may contribute at significant levels to the indoor volatile organic compounds (VOCs). In this study, we investigated the emission rate of VOCs and carbonyl compounds for 30 air fresheners and deodorizers by the standard small chamber test method (JIS A 1901). The total VOC (TVOC) emission rates of these household products ranged from the undetectable level (fragrances in the products account for the major part of the TVOC emissions. Based on the emission rates, the impacts on the indoor TVOC were estimated by the simple model with a volume of 17.4 m3 and a ventilation frequency of 0.5 times/h. The mean of the TVOC increment for the indoor air fresheners was 170 microg/m3, accounting for 40% of the current provisional target value, 400 microg/m3. These results suggest that daily use of household products can significantly influence the indoor air quality.

  6. 21 CFR 336.50 - Labeling of antiemetic drug products.

    Science.gov (United States)

    2010-04-01

    ... years of age. “Do not take this product, unless directed by a doctor, if you have a breathing problem... Section 336.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... under 12 years of age. “Do not give this product to children who have a breathing problem such as...

  7. Drug Production in Tertiary Health Institutions – Needs, Constraints ...

    African Journals Online (AJOL)

    The use of questionnaires was employed in the study covering all pharmacists in the pharmaceutical services department, pharmacy technicians and quality control technologist in the drug production unit of the hospital. It was unanimously agreed by the respondents that local drug production was necessary in tertiary ...

  8. Approved Animal Drug Products (Green Book)

    Data.gov (United States)

    U.S. Department of Health & Human Services — On November 16, 1988, the President of the United States signed into law the Generic Animal Drug and Patent Restoration Act (GADPTRA). Among its major provisions,...

  9. Development of deodorizing materials by radiation graft polymerization

    International Nuclear Information System (INIS)

    Sugo, Takanobu; Okamoto, Jiro; Fujiwara, Kunio; Sekiguchi, Hideo.

    1989-01-01

    With the development of society, the countermeasures for service water and sewerage in large cities and the environment preservation in industrial districts become difficult as their scale becomes larger. There are many unsolved problems, for example photochemical smog due to harmful gases, exhaust gas from automobiles, and smell of toilets and home waste water. The deodorizing materials used so far are mainly inorganic substances, and their ability of adsorbing harmful gases is very low. Besides, those are mostly granular, and limited in the formability. Therefore, it is expected to develop the fibrous adsorbent which has large adsorbing surface area and is easy to make filters. The chemical structures of the compounds having smell are shown. Eight legal bad smell substances which exert large influence to environment even in very small amount are designated. In this paper, the method of introducing functional radicals into existing fiber materials by the application of radiation graft polymerization process and the test of removing smelling compositions by using the obtained resin are reported. The experimental method, and the results of radiation graft polymerization, the adsorption of basic gases and acid gases, and gas flow test are described. (K.I.)

  10. 77 FR 71803 - Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug Products...

    Science.gov (United States)

    2012-12-04

    ... PET Drug Products--Questions and Answers.'' This guidance provides questions and answers that address.... 2201, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in... availability of a guidance entitled ``FDA Oversight of PET Drug Products--Questions and Answers.'' In 1997...

  11. Drug-device combination products: regulatory landscape and market growth.

    Science.gov (United States)

    Bayarri, L

    2015-08-01

    Combination products are therapeutic and diagnostic products that combine drugs, devices and/or biological products, leading to safer and more effective treatments thanks to careful and precise drug targeting, local administration and individualized therapy. These technologies can especially benefit patients suffering from serious diseases and conditions such as cancer, heart disease, multiple sclerosis and diabetes, among others. On the other hand, drug-device combination products have also introduced a new dynamic in medical product development, regulatory approval and corporate interaction. Due to the increasing integration of drugs and devices observed in the latest generation of combination products, regulatory agencies have developed specific competences and regulations over the last decade. Manufacturers are required to fully understand the specific requirements in each country in order to ensure timely and accurate market access of new combination products, and the development of combination products involves a very specific pattern of interactions between manufacturers and regulatory agencies. The increased sophistication of the products brought to market over the last couple of decades has accentuated the need to develop drugs and devices collaboratively using resources from both industries, fostering the need of business partnering and technology licensing. This review will provide a global overview of the market trends, as well as (in the last section) an analysis of the drug-device combination products approved by the FDA during the latest 5 years. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

  12. Air cleaning efficiency of deodorant materials under dynamic conditions: effect of air flow rate

    DEFF Research Database (Denmark)

    Mizutani, Chiyomi; Bivolarova, Mariya Petrova; Melikov, Arsen Krikor

    2014-01-01

    Unpleasant odor is a serious problem in hospitals and elderly facilities. One of the unpleasant odors is ammonia originating from human urine and sweat. The air cleaning efficiency of porous activated carbon fiber fabric which has been treated with acid, and porous activated carbon fiber fabric...... mixed with ammonia gas at a concentration of 20 ppm and velocities of 0.05, 0.15, 0.3 and 1.2 m/s. The activated carbon fibers treated with acid had a high deodorizing effect for ammonia (0.8) at a velocity of 0.05 m/s. The deodorizing effect of this material decreased with the increase in the velocity....... The porous activated carbon fiber fabric did not have a deodorant effect....

  13. Success rates for product development strategies in new drug development.

    Science.gov (United States)

    Dahlin, E; Nelson, G M; Haynes, M; Sargeant, F

    2016-04-01

    While research has examined the likelihood that drugs progress across phases of clinical trials, no research to date has examined the types of product development strategies that are the most likely to be successful in clinical trials. This research seeks to identify the strategies that are most likely to reach the market-those generated using a novel product development strategy or strategies that combine a company's expertise with both drugs and indications, which we call combined experience strategies. We evaluate the success of product development strategies in the drug development process for a sample of 2562 clinical trials completed by 406 US pharmaceutical companies. To identify product development strategies, we coded each clinical trial according to whether it consisted of an indication or a drug that was new to the firm. Accordingly, a clinical trial that consists of both an indication and a drug that were both new to the firm represents a novel product development strategy; indication experience is a product development strategy that consists of an indication that a firm had tested previously in a clinical trial, but with a drug that was new to the firm; drug experience is a product development strategy that consists of a drug that the firm had prior experience testing in clinical trials, but with an indication that was new to the firm; combined experience consists of both a drug and an indication that the firm had experience testing in clinical trials. Success rates for product development strategies across clinical phases were calculated for the clinical trials in our sample. Combined experience strategies had the highest success rate. More than three and a half percent (0·036) of the trials that combined experience with drugs and indications eventually reached the market. The next most successful strategy is drug experience (0·025) with novel strategies trailing closely (0·024). Indication experience strategies are the least successful (0·008

  14. 21 CFR 341.72 - Labeling of antihistamine drug products.

    Science.gov (United States)

    2010-04-01

    ..., unless directed by a doctor, if you have a breathing problem such as emphysema or chronic bronchitis, or... Section 341.72 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... product if you are taking sedatives or tranquilizers, without first consulting your doctor. Use caution...

  15. Progressive anticonvulsant hypersensitivity syndrome associated with change of drug product

    DEFF Research Database (Denmark)

    Sabroe, T.P.; Sabers, A.

    2008-01-01

    This report describes the laboratory and physical manifestations of lamotrigine-like toxicity in a young man with refractory epilepsy receiving lamotrigine presenting as anticonvulsant hypersensitivity syndrome (AHS) associated with an abrupt change of drug product Udgivelsesdato: 2008/6...

  16. Toward a generic approach for : Stress testing of drug substances and drug products

    NARCIS (Netherlands)

    Klick, Silke; Muijselaar, Pim G.; Waterval, Joop; Eichinger, Thomas; Korn, Christian; Gerding, Thijs K.; Debets, Alexander J.; Sänger-Van De Griend, Cari; Van Den Beld, Cas; Somsen, Govert W.; De Jong, Gerhardus J.

    The Impurity Profiling Group has developed a generic approach for conducting stress testing on drug substances and drug products. The proposed strategy is evaluated and verified with historical data and new experiments. Results demonstrate that the proposed approach is reasonable and generates

  17. 21 CFR 216.24 - Drug products withdrawn or removed from the market for reasons of safety or effectiveness.

    Science.gov (United States)

    2010-04-01

    .... Bromfenac sodium: All drug products containing bromfenac sodium. Butamben: All parenteral drug products...). Dexfenfluramine hydrochloride: All drug products containing dexfenfluramine hydrochloride. Diamthazole... dihydrostreptomycin sulfate. Dipyrone: All drug products containing dipyrone. Encainide hydrochloride: All drug...

  18. Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery

    Directory of Open Access Journals (Sweden)

    Nicholas Ekow Thomford

    2018-05-01

    Full Text Available The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of “active compound” has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of ‘organ-on chip’ and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug

  19. Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery.

    Science.gov (United States)

    Thomford, Nicholas Ekow; Senthebane, Dimakatso Alice; Rowe, Arielle; Munro, Daniella; Seele, Palesa; Maroyi, Alfred; Dzobo, Kevin

    2018-05-25

    The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of "active compound" has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of 'organ-on chip' and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug development. This review

  20. Lessons from innovation in drug-device combination products.

    Science.gov (United States)

    Couto, Daniela S; Perez-Breva, Luis; Saraiva, Pedro; Cooney, Charles L

    2012-01-01

    Drug-device combination products introduced a new dynamic on medical product development, regulatory approval, and corporate interaction that provide valuable lessons for the development of new generations of combination products. This paper examines the case studies of drug-eluting stents and transdermal patches to facilitate a detailed understanding of the challenges and opportunities introduced by combination products when compared to previous generations of traditional medical or drug delivery devices. Our analysis indicates that the largest barrier to introduce a new kind of combination products is the determination of the regulatory center that is to oversee its approval. The first product of a new class of combination products offers a learning opportunity for the regulator and the sponsor. Once that first product is approved, the leading regulatory center is determined, and the uncertainty about the entire class of combination products is drastically reduced. The sponsor pioneering a new class of combination products assumes a central role in reducing this uncertainty by advising the decision on the primary function of the combination product. Our analysis also suggests that this decision influences the nature (pharmaceutical, biotechnology, or medical devices) of the companies that will lead the introduction of these products into the market, and guide the structure of corporate interaction thereon. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Using Nonexperts for Annotating Pharmacokinetic Drug-Drug Interaction Mentions in Product Labeling: A Feasibility Study.

    Science.gov (United States)

    Hochheiser, Harry; Ning, Yifan; Hernandez, Andres; Horn, John R; Jacobson, Rebecca; Boyce, Richard D

    2016-04-11

    Because vital details of potential pharmacokinetic drug-drug interactions are often described in free-text structured product labels, manual curation is a necessary but expensive step in the development of electronic drug-drug interaction information resources. The use of nonexperts to annotate potential drug-drug interaction (PDDI) mentions in drug product label annotation may be a means of lessening the burden of manual curation. Our goal was to explore the practicality of using nonexpert participants to annotate drug-drug interaction descriptions from structured product labels. By presenting annotation tasks to both pharmacy experts and relatively naïve participants, we hoped to demonstrate the feasibility of using nonexpert annotators for drug-drug information annotation. We were also interested in exploring whether and to what extent natural language processing (NLP) preannotation helped improve task completion time, accuracy, and subjective satisfaction. Two experts and 4 nonexperts were asked to annotate 208 structured product label sections under 4 conditions completed sequentially: (1) no NLP assistance, (2) preannotation of drug mentions, (3) preannotation of drug mentions and PDDIs, and (4) a repeat of the no-annotation condition. Results were evaluated within the 2 groups and relative to an existing gold standard. Participants were asked to provide reports on the time required to complete tasks and their perceptions of task difficulty. One of the experts and 3 of the nonexperts completed all tasks. Annotation results from the nonexpert group were relatively strong in every scenario and better than the performance of the NLP pipeline. The expert and 2 of the nonexperts were able to complete most tasks in less than 3 hours. Usability perceptions were generally positive (3.67 for expert, mean of 3.33 for nonexperts). The results suggest that nonexpert annotation might be a feasible option for comprehensive labeling of annotated PDDIs across a broader

  2. Nano-sized crystalline drug production by milling technology.

    Science.gov (United States)

    Moribe, Kunikazu; Ueda, Keisuke; Limwikrant, Waree; Higashi, Kenjirou; Yamamoto, Keiji

    2013-01-01

    Nano-formulation of poorly water-soluble drugs has been developed to enhance drug dissolution. In this review, we introduce nano-milling technology described in recently published papers. Factors affecting the size of drug crystals are compared based on the preparation methods and drug and excipient types. A top-down approach using the comminution process is a method conventionally used to prepare crystalline drug nanoparticles. Wet milling using media is well studied and several wet-milled drug formulations are now on the market. Several trials on drug nanosuspension preparation using different apparatuses, materials, and conditions have been reported. Wet milling using a high-pressure homogenizer is another alternative to preparing production-scale drug nanosuspensions. Dry milling is a simple method of preparing a solid-state drug nano-formulation. The effect of size on the dissolution of a drug from nanoparticles is an area of fundamental research, but it is sometimes incorrectly evaluated. Here, we discuss evaluation procedures and the associated problems. Lastly, the importance of quality control, process optimization, and physicochemical characterization are briefly discussed.

  3. 75 FR 33312 - Indexing Structured Product Labeling for Human Prescription Drug and Biological Products; Request...

    Science.gov (United States)

    2010-06-11

    ...] Indexing Structured Product Labeling for Human Prescription Drug and Biological Products; Request for... Biologics Evaluation and Research (CBER) are indexing certain categories of information in product labeling for use as terms to search repositories of approved prescription medical product structured product...

  4. 21 CFR 310.509 - Parenteral drug products in plastic containers.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Parenteral drug products in plastic containers... Parenteral drug products in plastic containers. (a) Any parenteral drug product packaged in a plastic... parenteral drug product for intravenous use in humans that is packaged in a plastic immediate container on or...

  5. Penetuan Bilangan Iodin pada Hydrogenated Palm Kernel Oil (HPKO) dan Refined Bleached Deodorized Palm Kernel Oil (RBDPKO)

    OpenAIRE

    Sitompul, Monica Angelina

    2015-01-01

    Have been conducted Determination of Iodin Value by method titration to some Hydrogenated Palm Kernel Oil (HPKO) and Refined Bleached Deodorized Palm Kernel Oil (RBDPKO). The result of analysis obtained the Iodin Value in Hydrogenated Palm Kernel Oil (A) = 0,16 gr I2/100gr, Hydrogenated Palm Kernel Oil (B) = 0,20 gr I2/100gr, Hydrogenated Palm Kernel Oil (C) = 0,24 gr I2/100gr. And in Refined Bleached Deodorized Palm Kernel Oil (A) = 17,51 gr I2/100gr, Refined Bleached Deodorized Palm Kernel ...

  6. Japan kynol: Activated carbon base fiber, use light pattern deodorant sale; Kassei tanso seni wo shiyo. Usugata no dasshuzai hanbai

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-02-28

    The backbone manufacturer of the high function fiber, Japan kynol sells the deodorant (dassyu-irukakun) which used activated carbon fiber in late January. It is compared with grain-shaped activated carbon of the main stream with a deodorization material, and it is said that the space isn`t taken with a light pattern with a deodorization speed`s being early. It is sold in the center of the supermarket and the platform for a refrigerator and a locker, the pet house and the car. (translated by NEDO)

  7. "Product on Stopper" in a Lyophilized Drug Product: Cosmetic Defect or a Product Quality Concern?

    Science.gov (United States)

    Mehta, Shyam B; Roy, Shouvik; Yang, Han-Chang Cathy

    2018-06-01

    During manufacturing of a lyophilized drug product, operator errors in product handling during loading of product filled vials onto the lyophilizer can lead to a seemingly cosmetic defect which can impact certain critical quality attributes of finished product. In this study, filling of a formulated monoclonal antibody in vials was performed using a peristaltic pump filling unit, and subsequently, the product was lyophilized. After lyophilization, upon visual inspection, around 40% of vials had cosmetic defect with residual product around stopper of the vial and were categorized as "product on stopper" vials, whereas remaining 60% vials with no cosmetic defect were called "acceptable vials." Both groups of vials from 1 single batch were tested for critical quality attributes including protein concentration (ultraviolet absorbance at 280), residual moisture (Karl Fischer), sterility (membrane filtration), and container closure integrity (CCI) (blue dye ingress). Analysis of protein quality attributes such as aggregation, protein concentration, residual moisture showed no significant difference between vials with "product on stopper" and "acceptable vials." However, CCI of the "product on stopper" vials was compromised due to the presence of product around stopper of the vial. The results from this case study demonstrate the following 2 important findings: (1) that a seemingly cosmetic defect may impact product quality, compromising the integrity of the product and (2) that CCI test method can be used as an orthogonal method to sterility testing to evaluate sterility assurance of the product. The corrective action proposed to mitigate this defect is use of a larger sized vial that can potentially minimize this defect that arises because of product handling errors. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  8. Cell culture media impact on drug product solution stability.

    Science.gov (United States)

    Purdie, Jennifer L; Kowle, Ronald L; Langland, Amie L; Patel, Chetan N; Ouyang, Anli; Olson, Donald J

    2016-07-08

    To enable subcutaneous administration of monoclonal antibodies, drug product solutions are often needed at high concentrations. A significant risk associated with high drug product concentrations is an increase in aggregate level over the shelf-life dating period. While much work has been done to understand the impact of drug product formulation on aggregation, there is limited understanding of the link between cell culture process conditions and soluble aggregate growth in drug product. During cell culture process development, soluble aggregates are often measured at harvest using cell-free material purified by Protein A chromatography. In the work reported here, cell culture media components were evaluated with respect to their impact on aggregate levels in high concentration solution drug product during accelerated stability studies. Two components, cysteine and ferric ammonium citrate, were found to impact aggregate growth rates in our current media (version 1) leading to the development of new chemically defined media and concentrated feed formulations. The new version of media and associated concentrated feeds (version 2) were evaluated across four cell lines producing recombinant IgG4 monoclonal antibodies and a bispecific antibody. In all four cell lines, the version 2 media reduced aggregate growth over the course of a 12 week accelerated stability study compared with the version 1 media, although the degree to which aggregate growth decreased was cell line dependent. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:998-1008, 2016. © 2016 American Institute of Chemical Engineers.

  9. 75 FR 24394 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug...

    Science.gov (United States)

    2010-05-05

    ... [Docket No. FDA-2010-N-0002] Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug Application; Buquinolate; Coumaphos AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations by...

  10. Drugs from the Oceans: Marine Natural Products as Leads for Drug Discovery.

    Science.gov (United States)

    Altmann, Karl-Heinz

    2017-10-25

    The marine environment harbors a vast number of species that are the source of a wide array of structurally diverse bioactive secondary metabolites. At this point in time, roughly 27'000 marine natural products are known, of which eight are (were) at the origin of seven marketed drugs, mostly for the treatment of cancer. The majority of these drugs and also of drug candidates currently undergoing clinical evaluation (excluding antibody-drug conjugates) are unmodified natural products, but synthetic chemistry has played a central role in the discovery and/or development of all but one of the approved marine-derived drugs. More than 1000 new marine natural products have been isolated per year over the last decade, but the pool of new and unique structures is far from exhausted. To fully leverage the potential offered by the structural diversity of marine-produced secondary metabolites for drug discovery will require their broad assessment for different bioactivities and the productive interplay between new fermentation technologies, synthetic organic chemistry, and medicinal chemistry, in order to secure compound supply and enable lead optimization.

  11. 21 CFR 333.150 - Labeling of first aid antibiotic drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of first aid antibiotic drug products... First Aid Antibiotic Drug Products § 333.150 Labeling of first aid antibiotic drug products. (a... identifies the product as a “first aid antibiotic.” (b) Indications. The labeling of the product states...

  12. Package selection for moisture protection for solid, oral drug products.

    Science.gov (United States)

    Waterman, Kenneth C; MacDonald, Bruce C

    2010-11-01

    This review describes how best to select the appropriate packaging options for solid, oral drug products based on both chemical and physical stability, with respect to moisture protection. This process combines an accounting for the initial moisture content of dosage form components, moisture transfer into (out of) packaging based on a moisture vapor transfer rate (MVTR), and equilibration between drug products and desiccants based on their moisture sorption isotherms to provide an estimate of the instantaneous relative humidity (RH) within the packaging. This time-based RH is calculationally combined with a moisture-sensitive Arrhenius equation (determined using the accelerated stability assessment program, ASAP) to predict the drug product's chemical stability over time as a function of storage conditions and packaging options. While physical stability of dosage forms with respect to moisture has been less well documented, a process is recommended based on the threshold RH at which changes (e.g., dosage form dissolution, tablet hardness, drug form) become problematic. The overall process described allows packaging to be determined for a drug product scientifically, with the effect of any changes to storage conditions or packaging to be explicitly accounted for. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

  13. 21 CFR 344.52 - Labeling of ear drying aid drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of ear drying aid drug products. 344.52 Section 344.52 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Labeling of ear drying aid drug products. (a) Statement of identity. The labeling of the product contains...

  14. Recreational drug discovery: natural products as lead structures for the synthesis of smart drugs.

    Science.gov (United States)

    Appendino, Giovanni; Minassi, Alberto; Taglialatela-Scafati, Orazio

    2014-07-01

    Covering: up to December 2013. Over the past decade, there has been a growing transition in recreational drugs from natural materials (marijuana, hashish, opium), natural products (morphine, cocaine), or their simple derivatives (heroin), to synthetic agents more potent than their natural prototypes, which are sometimes less harmful in the short term, or that combine properties from different classes of recreational prototypes. These agents have been named smart drugs, and have become popular both for personal consumption and for collective intoxication at rave parties. The reasons for this transition are varied, but are mainly regulatory and commercial. New analogues of known illegal intoxicants are invisible to most forensic detection techniques, while the alleged natural status and the lack of avert acute toxicity make them appealing to a wide range of users. On the other hand, the advent of the internet has made possible the quick dispersal of information among users and the on-line purchase of these agents and/or the precursors for their synthesis. Unlike their natural products chemotypes (ephedrine, mescaline, cathinone, psilocybin, THC), most new drugs of abuse are largely unfamiliar to the organic chemistry community as well as to health care providers. To raise awareness of the growing plague of smart drugs we have surveyed, in a medicinal chemistry fashion, their development from natural products leads, their current methods of production, and the role that clandestine home laboratories and underground chemists have played in the surge of popularity of these drugs.

  15. Marine natural products: a new wave of drugs?

    Science.gov (United States)

    Montaser, Rana; Luesch, Hendrik

    2011-01-01

    The largely unexplored marine world that presumably harbors the most biodiversity may be the vastest resource to discover novel ‘validated’ structures with novel modes of action that cover biologically relevant chemical space. Several challenges, including the supply problem and target identification, need to be met for successful drug development of these often complex molecules; however, approaches are available to overcome the hurdles. Advances in technologies such as sampling strategies, nanoscale NMR for structure determination, total chemical synthesis, fermentation and biotechnology are all crucial to the success of marine natural products as drug leads. We illustrate the high degree of innovation in the field of marine natural products, which in our view will lead to a new wave of drugs that flow into the market and pharmacies in the future. PMID:21882941

  16. 21 CFR 250.250 - Hexachlorophene, as a component of drug and cosmetic products.

    Science.gov (United States)

    2010-04-01

    ... cosmetic products. 250.250 Section 250.250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Requirements for Drugs and Cosmetics § 250.250 Hexachlorophene, as a component of drug and cosmetic products... cosmetic products has expanded widely in recent years. It is used in such products because of its...

  17. Identification of antimycotic drugs transformation products upon UV exposure

    International Nuclear Information System (INIS)

    Casado, Jorge; Rodríguez, Isaac; Ramil, María; Cela, Rafael

    2015-01-01

    Highlights: • Evaluation of antimycotic drugs UV stabilities in model supports. • Simultaneous detection of precursor drugs and transformation products. • Transformation products identification from their scan, accurate MS/MS spectra. • Directed search of identified transformation products in sand and soil samples. • Preliminary toxicity estimations. - Abstract: The reactivity of three imidazolic, environmental persistent antimycotic drugs (clotrimazole, CTZ; ketoconazole, KTZ; and miconazole, MCZ) upon exposure to ultraviolet (UV) radiation is discussed. First, precursor compounds were immobilized in a silicone support which was further exposed to UV light at two different wavelengths: 254 and 365 nm. After solvent desorption, degradation kinetics of the precursor pharmaceuticals, identification of the arising transformation products (TPs) and evaluation of their time-course were investigated by liquid chromatography (LC) with quadrupole time-of-flight (QTOF) mass spectrometry (MS) detection. The three antimycotics displayed similar stabilities when exposed to 254 nm light; however, CTZ was significantly more stable than MCZ and KTZ when irradiated with the 365 nm lamp. TPs identified in silicone supports resulted from de-chlorination, cleavage, intra-molecular cyclization and hydroxylation reactions. Many of these species were also detected when exposing other solid matrices, such as sand and agricultural soil, previously spiked with target compounds, to UV light. The 50% estimated lethal concentration, calculated using the 48-h Daphnia magna test, for the two main TPs of CTZ and MCZ, at both wavelengths, were lower than those corresponding to the precursor drugs

  18. Identification of antimycotic drugs transformation products upon UV exposure

    Energy Technology Data Exchange (ETDEWEB)

    Casado, Jorge; Rodríguez, Isaac, E-mail: isaac.rodriguez@usc.es; Ramil, María; Cela, Rafael

    2015-05-30

    Highlights: • Evaluation of antimycotic drugs UV stabilities in model supports. • Simultaneous detection of precursor drugs and transformation products. • Transformation products identification from their scan, accurate MS/MS spectra. • Directed search of identified transformation products in sand and soil samples. • Preliminary toxicity estimations. - Abstract: The reactivity of three imidazolic, environmental persistent antimycotic drugs (clotrimazole, CTZ; ketoconazole, KTZ; and miconazole, MCZ) upon exposure to ultraviolet (UV) radiation is discussed. First, precursor compounds were immobilized in a silicone support which was further exposed to UV light at two different wavelengths: 254 and 365 nm. After solvent desorption, degradation kinetics of the precursor pharmaceuticals, identification of the arising transformation products (TPs) and evaluation of their time-course were investigated by liquid chromatography (LC) with quadrupole time-of-flight (QTOF) mass spectrometry (MS) detection. The three antimycotics displayed similar stabilities when exposed to 254 nm light; however, CTZ was significantly more stable than MCZ and KTZ when irradiated with the 365 nm lamp. TPs identified in silicone supports resulted from de-chlorination, cleavage, intra-molecular cyclization and hydroxylation reactions. Many of these species were also detected when exposing other solid matrices, such as sand and agricultural soil, previously spiked with target compounds, to UV light. The 50% estimated lethal concentration, calculated using the 48-h Daphnia magna test, for the two main TPs of CTZ and MCZ, at both wavelengths, were lower than those corresponding to the precursor drugs.

  19. Prudent Use of Veterinary Drugs: Impact on Safe Animal Products ...

    African Journals Online (AJOL)

    Like any other therapeutic compounds, veterinary drugs are used to alleviate diseases in animals as either therapeutic or prophylactic compounds for specific disease entities. They can also be used as production aids in food producing animals to increase market sale of these animals whereby the producers save on the ...

  20. 21 CFR 350.50 - Labeling of antiperspirant drug products.

    Science.gov (United States)

    2010-04-01

    ...: ‘dampness,’ ‘perspiration,’ ‘sweat,’ ‘sweating,’ or ‘wetness’] due to stress”. (3) For products that... this chapter for definition of bullet. (ii) The warning required by § 369.21 of this chapter for drugs...

  1. Production of drug nanosuspensions: effect of drug physical properties on nanosizing efficiency.

    Science.gov (United States)

    Liu, Tao; Müller, Rainer H; Möschwitzer, Jan P

    2018-02-01

    Drug nanosuspension is one of the established methods to improve the bioavailability of poorly soluble drugs. Drug physical properties aspect (morphology, solid state, starting size et al) is a critical parameter determining the production efficiency. Some drug modification approaches such as spray-drying were proved to improve the millability of drug powders. However, the mechanism behind those improved performances is unclear. This study is to systematically investigate the influence of those physical properties. Five different APIs (active pharmaceutical ingredients) with different millabilities, i.e. resveratrol, hesperetin, glibenclamide, rutin, and quercetin, were processed by standard high pressure homogenization (HPH), wet bead milling (WBM), and a combinative method of spray-drying and HPH. Smaller starting sizes of certain APIs could accelerate the particle size reduction velocity during both HPH and WBM processes. Spherical particles were observed for almost all spray-dried powders (except spray-dried hesperetin) after spray-drying. The crystallinity of some spray-dried samples such as rutin and glibenclamide became much lower than their corresponding unmodified powders. Almost all spray-dried drug powders after HPH processes could lead to smaller nanocrystal particle size than unmodified APIs. The modified microstructure instead of solid state after spray-drying explained the potential reason for improved nanosizing efficiency. In addition, the contribution of starting size on the production efficiency was also critical according to both HPH and WBM results.

  2. Tuberculosis drug issues: prices, fixed-dose combination products and second-line drugs.

    Science.gov (United States)

    Laing, R O; McGoldrick, K M

    2000-12-01

    Access to tuberculosis drugs depends on multiple factors. Selection of a standard list of TB drugs to procure is the first step. This paper reviews the advantages and disadvantages of procuring and using fixed-dose combination (FDC) products for both the intensive and continuation phases of treatment. The major advantages are to prevent the emergence of resistance, to simplify logistic management and to reduce costs. The major disadvantage is the need for the manufacturers to assure the quality of these FDCs by bioavailability testing. The paper reports on the inclusion of second-line TB drugs in the 1999 WHO Essential Drug List (EDL). The need to ensure that these drugs are used within established DOTS-Plus programs is stressed. The price of TB drugs is determined by many factors, including producer prices, local taxes and duties as well as mark-ups and fees. TB drug prices for both the public and private sectors from industrialized and developing countries are reported. Price trends over time are also reported. The key findings of this study are that TB drug prices have generally declined in developing countries while they have increased in developed countries, both for the public and private sectors. Prices vary between countries, with the US paying as much as 95 times the price paid in a specific developing country. The prices of public sector first-line TB drugs vary little between countries, although differences do exist due to the procurement methods used. The price of tuberculin, a diagnostic agent, has increased dramatically in the US, with substantial inter-country variations in price. The paper suggests that further research is necessary to identify the reasons for the price disparities and changes over time, and suggests methods which can be used by National Tuberculosis Programme managers to ensure availability of quality assured TB drugs at low prices.

  3. FDA's requirements for radiation dosimetry of radiopharmaceutical drug products

    International Nuclear Information System (INIS)

    Abel, N.M.

    1986-01-01

    The primary concern of the Office of Drug Research and Review of the Food and Drug Administration in the field of radiation dosimetry is to ensure that radiopharmaceutical drug products are safe when used as investigational drugs (INDs) and are both safe and effective when a new drug application (NDA) is approved. In order to accomplish this, the sponsor of either an IND or applicant in the case of NDA must provide information that clearly describes the radiation dose that a patient will receive from the administration of the drug. The submitted numerical estimates of the radiation dose should be based on an absorbed fraction method of radiation dose calculation, such as the system set forth by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine or the system set forth by the International Commission on Radiological Protection (ICRP). This presentation will describe in detail the data that a sponsor of an IND needs to submit to satisfy the regulatory requirements. Examples will be given of common mistakes and omissions by sponsors in their presentation of data

  4. Cumulative exposure to phthalates from phthalate-containing drug products

    DEFF Research Database (Denmark)

    Ennis, Zandra Nymand; Broe, Anne; Pottegård, Anton

    2018-01-01

    European regulatory limit of exposure ranging between 380-1710 mg/year throughout the study period. Lithium-products constituted the majority of dibutyl phthalate exposure. Diethyl phthalate exposure, mainly caused by erythromycin, theophylline and diclofenac products, did not exceed the EMA regulatory...... to quantify annual cumulated phthalate exposure from drug products among users of phthalate-containing oral medications in Denmark throughout the period of 2004-2016. METHODS: We conducted a Danish nationwide cohort study using The Danish National Prescription Registry and an internal database held...

  5. A basic study on the development of deodorants using pine needle oil

    Energy Technology Data Exchange (ETDEWEB)

    Doh, K.S.; Lee, H.J. [Department of Chemical Engineering, Soongsil University, Seoul (Korea, Republic of); Kim, D.K. [Chemical Technology Division, Korea Research Institute of Chemical Technology, Taejon (Korea, Republic of)

    1997-11-01

    The basic study on the development of deodorant made from pine needle oil was performed. The pine needle oil(PNO) was analysed using GC, GC/MS and FT-1R analyzer for analysis of chemical concentration, chemical components and structure. The analysis results obtained from GC and GC/MS analyzer were composed to main components of {alpha},{beta}-Pinene(C{sub 10}H{sub 16}), 3-Carene (C{sub 10}H{sub 16}), {Upsilon}-terpinene(C{sub 10}H{sub 16}) and terpinolene(C{sub 10}H{sub 16}), etc. Also, the concentration of heavy metals analysed from AAS analyzer. The COD and BOD concentration of landfill leachate with pine needle oil were surveyed. As a results, the pine needle oil extracted from pine needles can be used to remove bad smells of wastes as a deodorant. (author). 13 refs., 3 figs., 3 tabs.

  6. 21 CFR 20.2 - Production of records by Food and Drug Administration employees.

    Science.gov (United States)

    2010-04-01

    ... upon an officer or employee of the Food and Drug Administration commanding the production of any record... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Production of records by Food and Drug Administration employees. 20.2 Section 20.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

  7. A primer of drug safety surveillance: an industry perspective. Part II: Product labeling and product knowledge.

    Science.gov (United States)

    Allan, M C

    1992-01-01

    To place the fundamentals of clinical drug safety surveillance in a conceptual framework that will facilitate understanding and application of adverse drug event data to protect the health of the public and support a market for pharmaceutical manufacturers' products. Part II of this series discusses specific issues regarding product labeling, such as developing the labeling, changing the labeling, and the legal as well as commercial ramifications of the contents of the labeling. An adverse event report scenario is further analyzed and suggestions are offered for maintaining the product labeling as an accurate reflection of the drug safety surveillance data. This article also emphasizes the necessity of product knowledge in adverse event database management. Both scientific and proprietary knowledge are required. Acquiring product knowledge is a part of the day-to-day activities of drug safety surveillance. A knowledge of the history of the product may forestall adverse publicity, as shown in the illustration. This review uses primary sources from the federal laws (regulations), commentaries, and summaries. Very complex topics are briefly summarized in the text. Secondary sources, ranging from newspaper articles to judicial summaries, illustrate the interpretation of adverse drug events and opportunities for drug safety surveillance intervention. The reference materials used were articles theoretically or practically applicable in the day-to-day practice of drug safety surveillance. The role of clinical drug safety surveillance in product monitoring and drug development is described. The process of drug safety surveillance is defined by the Food and Drug Administration regulations, product labeling, product knowledge, and database management. Database management is subdivided into the functions of receipt, retention, retrieval, and review of adverse event reports. Emphasis is placed on the dynamic interaction of the components of the process. Suggestions are offered

  8. Penentuan Kadar Phosfor dari Crude Palm Oil (CPO) dan Refened Of Bleached Deodorized Palm Olein (RBDPO)

    OpenAIRE

    Ulfah, Afhami

    2015-01-01

    Analysis has been performed Determination of Phosphorus Levels on Crude Plam Oil (CPO) and Refened Bleaching Deodorized Plam Olein (RBDPO) in PT.SMART.Tbk Medan-Belawan. Determination of phosphorus content in CPO and RBDPO is performed using UV-Visible Spectofotometry. Result obtained phosphorus levels on CPO is 11, 1243 ppm and phosphorus levels on RBDPO is 2, 5837 ppm. This result indicates that the phosphorus in the CPO and RBDPO standards are a maximum of 30 ppm for CPO ...

  9. 21 CFR 347.50 - Labeling of skin protectant drug products.

    Science.gov (United States)

    2010-04-01

    ... omitted. (f) Products containing only cocoa butter, petrolatum, or white petrolatum identified in § 347.10... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of skin protectant drug products. 347.50... (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 347...

  10. 78 FR 65904 - Permanent Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products

    Science.gov (United States)

    2013-11-04

    ... Manufacturing of Certain Drug or Biological Products AGENCY: Food and Drug Administration, HHS. ACTION: Proposed.... The Fabrazyme shortage resulted from contamination at the manufacturing [[Page 65910

  11. Potential of Continuous Manufacturing for Liposomal Drug Products.

    Science.gov (United States)

    Worsham, Robert D; Thomas, Vaughan; Farid, Suzanne S

    2018-05-21

    Over the last several years, continuous manufacturing of pharmaceuticals has evolved from bulk APIs and solid oral dosages into the more complex realm of biologics. The development of continuous downstream processing techniques has allowed biologics manufacturing to realize the benefits (e.g. improved economics, more consistent quality) that come with continuous processing. If relevant processing techniques and principles are selected, the opportunity arises to develop continuous manufacturing designs for additional pharmaceutical products including liposomal drug formulations. Liposome manufacturing has some inherent aspects that make it favorable for a continuous process. Other aspects such as formulation refinement, materials of construction, and aseptic processing need development, but present an achievable challenge. This paper reviews the current state of continuous manufacturing technology applicable to liposomal drug product manufacturing and an assessment of the challenges and potential of this application. This article is protected by copyright. All rights reserved.

  12. Liposomal Drug Product Development and Quality: Current US Experience and Perspective.

    Science.gov (United States)

    Kapoor, Mamta; Lee, Sau L; Tyner, Katherine M

    2017-05-01

    Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug's pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.

  13. Characterization of SNARE Cleavage Products Generated by Formulated Botulinum Neurotoxin Type-A Drug Products

    Directory of Open Access Journals (Sweden)

    Jack Xie

    2010-08-01

    Full Text Available The study evaluated substrate cleavage product(s generated by three botulinum neurotoxin serotype A (BoNT/A medicinal drug products utilizing a novel and highly specific, light-chain activity, high-performance liquid chromatography (LCA-HPLC method. Samples were reacted with a commercially available BoNT/A fluorescent substrate derived from the SNAP-25 sequence. Reaction products were separated by reversed-phase HPLC. The method detected an atypical cleavage pattern by one of the formulated drug products. IncobotulinumtoxinA produced two cleavage fragments rather than the single fragment typically generated by BoNT/A. Identification confirmed the secondary cleavage at a position corresponding to SNAP-25 Arg198–Ala199 (normal BoNT/A cleavage is Gln197–Arg198. Arg198–Ala199 is also the cleavage site for trypsin and serotype C toxin. Normal cleavage was observed for all other BoNT/A drug product samples, as well as 900-kD and 150-kD bulk toxin BoNT/A. The reason for this unexpected secondary cleavage pattern by one formulated BoNT/A drug product is unknown. Possible explanations include a contaminating protease and/or damage to the 150-kD type-A toxin causing nonspecific substrate recognition and subsequent cleavage uncharacteristic of type-A toxin. The BoNT/A drug products were also analyzed via the LCA-HPLC assay using a commercial BoNT/C fluorescent substrate derived from the syntaxin sequence. Cleavage of the serotype C substrate by incobotulinumtoxinA was also confirmed whilst neither of the other drug products cleaved the syntaxin substrate.

  14. Structure-based synthesis from natural products to drug prototypes

    International Nuclear Information System (INIS)

    Hanessian, S.

    2009-01-01

    X-Ray crystallographic data available from complexes of natural and synthetic molecules with the enzyme thrombin has aided to the design and synthesis of truncated and hybrid molecules exhibiting excellent inhibition in vitro. The vital importance of natural products for the well-being of man has been known lor millennia. Their therapeutic benefits to alleviate pain or cure diseases continue to rank natural products among the primary sources of potential drugs. Great advances have been made in the methods of isolation, identification, and structure elucidation of some of the most complex natural products in recent years. The advent of molecular biology and genetic mapping has also aided in our understanding of the intriguing biosynthetic pathways leading to various classes of therapeutically relevant antibiotic, anticancer, and related natural products. Elegant and practical methodology has been developed leading to the total synthesis of virtually every class of medicinally important natural product. In some cases, natural products or their chemically modified congeners have been manufactured by total synthesis on an industrial level which is a testament to the ingenuity of process chemists. In spite of their potent activities HI enzymatic ox receptor-mediated assays, not all natural products are amenable to being developed as marketable drags. In many instances unfavorable pharmacological effects cannot be overcome without drastic structural and functional modifications, which may also result in altered efficacy. Structure modification through truncation, functional group variations, isosteric replacements, and skeletal rigidifications aided by molecular modeling, X ray crystallography of protein targets, or NMR data are valid objectives in the context of small molecule drug discovery starting with bioactive natural products. A large proportion of these pertain to chemotherapeutic agents against cancer

  15. Interdisciplinary researches for potential developments of drugs and natural products

    Directory of Open Access Journals (Sweden)

    Arunrat Chaveerach

    2017-04-01

    Full Text Available Developments of drugs or natural products from plants are possibly made, simple to use and lower cost than modern drugs. The development processes can be started with studying local wisdom and literature reviews to choose the plants which have long been used in diverse areas, such as foods, traditional medicine, fragrances and seasonings. Then those data will be associated with scientific researches, namely plant collection and identification, phytochemical screening by gas chromatography-mass spectrometry, pharmacological study/review for their functions, and finally safety and efficiency tests in human. For safety testing, in vitro cell toxicity by cell viability assessment and in vitro testing of DNA breaks by the comet assay in human peripheral blood mononuclear cells can be performed. When active chemicals and functions containing plants were chosen with safety and efficacy for human uses, then, the potential medicinal natural products will be produced. Based on these procedures, the producing cost will be cheaper and the products can be evaluated for their clinical properties. Thus, the best and lowest-priced medicines and natural products can be distributed worldwide.

  16. Interdisciplinary researches for potential developments of drugs and natural products

    Institute of Scientific and Technical Information of China (English)

    Arunrat Chaveerach; Runglawan Sudmoon; Tawatchai Tanee

    2017-01-01

    Developments of drugs or natural products from plants are possibly made,simple to use and lower cost than modern drugs.The development processes can be started with studying local wisdom and literature reviews to choose the plants which have long been used in diverse areas,such as foods,traditional medicine,fragrances and seasonings.Then those data will be associated with scientific researches,namely plant collection and identification,phytochemical screening by gas chromatography-mass spectrometry,pharmacological study/review for their functions,and finally safety and efficiency tests in human.For safety testing,in vitro cell toxicity by cell viability assessment and in vitro testing of DNA breaks by the comet assay in human peripheral blood mononuclear cells can be performed.When active chemicals and functions containing plants were chosen with safety and efficacy for human uses,then,the potential medicinal natural products will be produced.Based on these procedures,the producing cost will be cheaper and the products can be evaluated for their clinical properties.Thus,the best and lowest-priced medicines and natural products can be distributed worldwide.

  17. Natural Products as Leads in Schistosome Drug Discovery

    Directory of Open Access Journals (Sweden)

    Bruno J. Neves

    2015-01-01

    Full Text Available Schistosomiasis is a neglected parasitic tropical disease that claims around 200,000 human lives every year. Praziquantel (PZQ, the only drug recommended by the World Health Organization for the treatment and control of human schistosomiasis, is now facing the threat of drug resistance, indicating the urgent need for new effective compounds to treat this disease. Therefore, globally, there is renewed interest in natural products (NPs as a starting point for drug discovery and development for schistosomiasis. Recent advances in genomics, proteomics, bioinformatics, and cheminformatics have brought about unprecedented opportunities for the rapid and more cost-effective discovery of new bioactive compounds against neglected tropical diseases. This review highlights the main contributions that NP drug discovery and development have made in the treatment of schistosomiasis and it discusses how integration with virtual screening (VS strategies may contribute to accelerating the development of new schistosomidal leads, especially through the identification of unexplored, biologically active chemical scaffolds and structural optimization of NPs with previously established activity.

  18. 78 FR 75570 - Guidance for Industry on New Animal Drugs and New Animal Drug Combination Products Administered...

    Science.gov (United States)

    2013-12-12

    ... Guidance for Industry (GFI) 209, ``The Judicious Use of Medically Important Antimicrobial Drugs in Food... of certain antimicrobial new animal drug products who are interested in revising conditions of use... Medically Important Antimicrobial Drugs in Food-Producing Animals,'' and to set timelines for stakeholders...

  19. 75 FR 65565 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications...

    Science.gov (United States)

    2010-10-26

    ... 558 [Docket No. FDA-2010-N-0002] Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications; Aklomide; Levamisole Hydrochloride; Nitromide and Sulfanitran AGENCY...) is amending the animal drug regulations by removing those portions that reflect approval of eight new...

  20. 21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Imprinting of solid oral dosage form drug products... AS SAFE AND EFFECTIVE AND NOT MISBRANDED General Provisions § 330.3 Imprinting of solid oral dosage form drug products. A requirement to imprint an identification code on solid oral dosage form drug...

  1. 77 FR 71006 - Sodium Nitrite Injection and Sodium Thiosulfate Injection Drug Products Labeled for the Treatment...

    Science.gov (United States)

    2012-11-28

    ... poisoning and unapproved injectable drug products containing sodium thiosulfate labeled for the treatment of... for the treatment of cyanide poisoning are new drugs that require approved new drug applications (NDAs... Injection and Sodium Thiosulfate Injection drug product, labeled for treatment of acute cyanide poisoning...

  2. Scientific workflows as productivity tools for drug discovery.

    Science.gov (United States)

    Shon, John; Ohkawa, Hitomi; Hammer, Juergen

    2008-05-01

    Large pharmaceutical companies annually invest tens to hundreds of millions of US dollars in research informatics to support their early drug discovery processes. Traditionally, most of these investments are designed to increase the efficiency of drug discovery. The introduction of do-it-yourself scientific workflow platforms has enabled research informatics organizations to shift their efforts toward scientific innovation, ultimately resulting in a possible increase in return on their investments. Unlike the handling of most scientific data and application integration approaches, researchers apply scientific workflows to in silico experimentation and exploration, leading to scientific discoveries that lie beyond automation and integration. This review highlights some key requirements for scientific workflow environments in the pharmaceutical industry that are necessary for increasing research productivity. Examples of the application of scientific workflows in research and a summary of recent platform advances are also provided.

  3. Production of drug-loaded polymeric nanoparticles by electrospraying technology.

    Science.gov (United States)

    Sosnik, Alejandro

    2014-09-01

    The pharmaceutical industry struggles with high attrition. The outbreak of pharmaceutical micro/nanotechnology has been fundamental to overcome several (bio)pharmaceutic drawbacks of drugs such as poor aqueous solubility, physicochemical instability, short half life, inappropriate biodistribution and toxicity. The spatiotemporal release of drugs directly in the site of action and the restriction of the systemic exposure by means of nanotechnology has notoriously improved drug safety ratios. At the same time, the development of production methods that are cost-effective, scalable and reproducible under industrial settings becomes crucial to ensure the clinical translation of any development. The electrospraying process, also known as electrohydrodynamic atomization (EHDA), is a single-stage technique of liquid atomization by means of electrical forces that enables the generation of micro/nanoparticles with especially narrow size distribution. EHDA is based on the ability of an electric field to deform the interface of a liquid drop and break it into smaller mono-disperse droplets. The main advantageous features over conventional methods are the possibility to produce particles without the use of surfactants, at ambient temperature and pressure and with maximum encapsulation efficiency due to the absence of an external medium that allows the migration and/or dissolution of water-soluble cargos. In addition, the mild conditions are optimal for the encapsulation of thermo-sensitive cargos. The present article overviews the applications of this technology for the production of nano-drug delivery systems and discusses its key role to support the transfer of a broad spectrum of nanomedicines to the market.

  4. 76 FR 60504 - Guidance for Industry on Time and Extent Applications for Nonprescription Drug Products...

    Science.gov (United States)

    2011-09-29

    ... monograph need not obtain FDA approval before marketing if their drug product meets the conditions in part... introduce into the United States an OTC drug product that had been marketed solely in a foreign country...

  5. Deodorization of Arthrospira platensis biomass for further scale-up food applications.

    Science.gov (United States)

    Cuellar-Bermúdez, Sara P; Barba-Davila, Bertha; Serna-Saldivar, Sergio O; Parra-Saldivar, Roberto; Rodriguez-Rodriguez, José; Morales-Davila, Sandra; Goiris, Koen; Muylaert, Koenraad; Chuck-Hernández, Cristina

    2017-12-01

    Given the importance of A. platensis as a potential food protein source, we describe an affordable deodorization process that does not significantly affect the nutritional value of algae biomass. Ethanol, acetone or hexane were used to deodorize algae biomass and then to identify the profile of volatile compounds associated with its distinctive odor. Sensorial characteristics were improved in the biomass cake after the proposed solvent extraction. Panelists identified the ethanolic extract with the most pronounced algae-related odor. Gas chromatography-mass spectrometry analysis showed that a mixture of 20 different compounds derived from fatty acids and amino acids contributed to the characteristic smell of A. platensis biomass. The results of the present study show that the ethanol solvent-free A. platensis biomass contained > 600 g kg -1 protein,  65% in vitro protein digestibility, similar to the original biomass. The Fourier transform infrared spectroscopy secondary protein structure was comparable among samples, indicating that the only change after ethanol extraction was a reduction of the algae smell. The various extraction procedures investigated in the present study were effective in deodorizing the algae biomass. The most effective protocol was the removal of odoriferous compounds with ethanol. This particular procedure yielded an algae biomass with an improved sensorial traits. The results of the present study should help with the identification of odoriferous compounds derived from fatty acids, pigments and proteins associated with A. platensis. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  6. Impurities in Drug Products and Active Pharmaceutical Ingredients.

    Science.gov (United States)

    Kątny, M; Frankowski, M

    2017-05-04

    Analytical methods should be selective and fast. In modern times, scientists strive to meet the criteria of green chemistry, so they choose analytical procedures that are as short as possible and use the least toxic solvents. It is quite obvious that the products intended for human consumption should be characterized as completely as possible. The safety of a drug is dependent mainly on the impurities that it contains. High pressure liquid chromatography and ultra-high pressure liquid chromatography have been proposed as the main techniques for forced degradation and impurity profiling. The aim of this article was to characterize the relevant classification of drug impurities and to review the methods of impurities determination for atorvastatin (ATV) and duloxetine (DLX) (both in active pharmaceutical ingredients and in different dosage forms). These drugs have an impact on two systems of the human body: cardiac and nervous. Simple characteristics of ATV and DLX, their properties and specificity of action on the human body, are also included in this review. The analyzed pharmaceuticals-ATV (brand name Lipiron) and DLX (brand name Cymbalta)-were selected for this study based on annual rankings prepared by Information Medical Statistics.

  7. Patient centric drug product design in modern drug delivery as an opportunity to increase safety and effectiveness.

    Science.gov (United States)

    Stegemann, Sven

    2018-06-01

    The advances in drug delivery technologies have enabled pharmaceutical scientists to deliver a drug through various administration routes and optimize the drug release and absorption. The wide range of drug delivery systems and dosage forms represent a toolbox of technology for the development of pharmaceutical drug products but might also be a source of medication errors and nonadherence. Patient centric drug product development is being suggested as an important factor to increase therapeutic outcomes. Areas covered: Patients have impaired health and potentially disabilities and they are not medical or pharmaceutical experts but are requested to manage complex therapeutic regimens. As such the application of technology should also serve to reduce complexity, build on patients' intuition and ease of use. Patients form distinct populations based on the targeted disease, disease cluster or age group with specific characteristics or therapeutic contexts. Expert opinion: Establishing a target product and patient profile is essential to guide drug product design development. Including the targeted patient populations in the process is a prerequisite to achieve patient-centric pharmaceutical drug product design. Addressing the needs early on in the product design process, will create more universal design, avoiding the necessity for multiple product presentations to cover the different patient populations.

  8. Allergic contact dermatitis from the synthetic fragrances Lyral and acetyl cedrene in separate underarm deodorant preparations.

    Science.gov (United States)

    Handley, J; Burrows, D

    1994-11-01

    The case is reported of a 28-year-old man who developed allergic contact dermatitis from 2 synthetic fragrance ingredients, Lyral (3- and 4-(4-hydroxy-4-methylpentyl)-3-cyclohexene-1-aldehyde) and acetyl cedrene, in separate underarm deodorant preparations. The implications of the patient's negative patch test reactions to the European standard series (Trolab) and cosmetics and fragrance series (both Chemotechnique Diagnostics) are discussed. The importance is stressed of patch testing with the patient's own preparations when cosmetic dermatitis is suspected, and of identifying and reporting offending fragrance ingredients, with a view possibly to updating the European standard series and commercially available cosmetics and fragrance series.

  9. 21 CFR 212.110 - How must I maintain records of my production of PET drugs?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false How must I maintain records of my production of PET drugs? 212.110 Section 212.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... those not stored at the inspected establishment, must be legible, stored to prevent deterioration or...

  10. 78 FR 23273 - Determination That the OXYCONTIN (Oxycodone Hydrochloride) Drug Products Covered by New Drug...

    Science.gov (United States)

    2013-04-18

    ... mitigation strategy (REMS) http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationfor... Blueprint for Prescriber Education for Extended- Release and Long-Acting Opioid Analgesics'' ( http://www...

  11. An Intercompany Perspective on Biopharmaceutical Drug Product Robustness Studies.

    Science.gov (United States)

    Morar-Mitrica, Sorina; Adams, Monica L; Crotts, George; Wurth, Christine; Ihnat, Peter M; Tabish, Tanvir; Antochshuk, Valentyn; DiLuzio, Willow; Dix, Daniel B; Fernandez, Jason E; Gupta, Kapil; Fleming, Michael S; He, Bing; Kranz, James K; Liu, Dingjiang; Narasimhan, Chakravarthy; Routhier, Eric; Taylor, Katherine D; Truong, Nobel; Stokes, Elaine S E

    2018-02-01

    The Biophorum Development Group (BPDG) is an industry-wide consortium enabling networking and sharing of best practices for the development of biopharmaceuticals. To gain a better understanding of current industry approaches for establishing biopharmaceutical drug product (DP) robustness, the BPDG-Formulation Point Share group conducted an intercompany collaboration exercise, which included a bench-marking survey and extensive group discussions around the scope, design, and execution of robustness studies. The results of this industry collaboration revealed several key common themes: (1) overall DP robustness is defined by both the formulation and the manufacturing process robustness; (2) robustness integrates the principles of quality by design (QbD); (3) DP robustness is an important factor in setting critical quality attribute control strategies and commercial specifications; (4) most companies employ robustness studies, along with prior knowledge, risk assessments, and statistics, to develop the DP design space; (5) studies are tailored to commercial development needs and the practices of each company. Three case studies further illustrate how a robustness study design for a biopharmaceutical DP balances experimental complexity, statistical power, scientific understanding, and risk assessment to provide the desired product and process knowledge. The BPDG-Formulation Point Share discusses identified industry challenges with regard to biopharmaceutical DP robustness and presents some recommendations for best practices. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  12. 21 CFR 335.50 - Labeling of antidiarrheal drug products.

    Science.gov (United States)

    2010-04-01

    ... problem”. (iii) “Ask a doctor or pharmacist before use if you are taking any drug for [bullet... Section 335.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... identified in § 335.10. (i) “Do not use if you have [bullet] bloody or black stool”. (ii) “Ask a doctor...

  13. The production and sales of anti-tuberculosis drugs in China.

    Science.gov (United States)

    Huang, Yang-Mu; Zhao, Qi-Peng; Ren, Qiao-Meng; Peng, Dan-Lu; Guo, Yan

    2016-10-04

    Tuberculosis (TB) is a major infectious disease globally. Adequate and proper use of anti-TB drugs is essential for TB control. This study aims to study China's production capacity and sales situation of anti-TB drugs, and to further discuss the potential for China to contribute to global TB control. The production data of anti-TB drugs in China from 2011 to 2013 and the sales data from 2010 to 2014 were extracted from Ministry of Industry and Information Technology database of China and IMS Health database, respectively. The number of drugs was standardized to the molecular level of the key components before calculating. All data were described and analyzed by Microsoft Excel. First-line drugs were the majority in both sales (89.5 %) and production (92.3 %) of anti-TB drugs in China. The production of rifampicin held the majority share in active pharmaceutical ingredients (APIs) and finished products, whilst ethambutol and pyrazinamide were the top two sales in finished products. Fixed-dose combinations only held small percentages in total production and sales weight, though a slight increase was observed. The production and sales of streptomycin showed a tendency of decrease after 2012. The trends and proportion of different anti-TB drugs were similar in production and sales, however, the production weight was much larger than that of sales, especially for rifampicin and isoniazid. First-line drugs were the predominant medicine produced and used in China. While the low production and sales of the second-line TB drugs and FDCs rose concerns for the treatment of multiple drug resistant TB. The redundant production amount, as well as the prompt influence of national policy on drug production and sales, indicated the potential for China to better contribute to global TB control.

  14. Automatic deodorizing system for waste water from radioisotope facilities using an ozone generator

    International Nuclear Information System (INIS)

    Kawamura, Hiroko; Hirata, Yasuki

    2002-01-01

    We applied an ozone generator to sterilize and to deodorize the waste water from radioisotope facilities. A small tank connected to the generator is placed outside of the drainage facility founded previously, not to oxidize the other apparatus. The waste water is drained 1 m 3 at a time from the tank of drainage facility, treated with ozone and discharged to sewer. All steps proceed automatically once the draining work is started remotely in the office. The waste water was examined after the ozone treatment for 0 (original), 0.5, 1.0, 1.5 and 2.0 h. Regarding original waste water, the sum of coliform groups varied with every examination repeated - probably depend on the colibacilli used in experiments; hydrogen sulfide, biochemical oxygen demand and the offensive odor increased with increasing coliform groups. The ozone treatment remarkably decreased hydrogen sulfide and the offensive odor, decreased coliform groups when the original water had rich coliforms. (author)

  15. Automatic deodorizing system for waste water from radioisotope facilities using an ozone generator

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Hiroko; Hirata, Yasuki [Kyushu Univ., Fukuoka (Japan). Radioisotope Center; Taguchi, Kenji [Riken Co. Ltd., Kitakyushu, Fukuoka (Japan)

    2002-03-01

    We applied an ozone generator to sterilize and to deodorize the waste water from radioisotope facilities. A small tank connected to the generator is placed outside of the drainage facility founded previously, not to oxidize the other apparatus. The waste water is drained 1 m{sup 3} at a time from the tank of drainage facility, treated with ozone and discharged to sewer. All steps proceed automatically once the draining work is started remotely in the office. The waste water was examined after the ozone treatment for 0 (original), 0.5, 1.0, 1.5 and 2.0 h. Regarding original waste water, the sum of coliform groups varied with every examination repeated - probably depend on the colibacilli used in experiments; hydrogen sulfide, biochemical oxygen demand and the offensive odor increased with increasing coliform groups. The ozone treatment remarkably decreased hydrogen sulfide and the offensive odor, decreased coliform groups when the original water had rich coliforms. (author)

  16. Protein Complex Production from the Drug Discovery Standpoint.

    Science.gov (United States)

    Moarefi, Ismail

    2016-01-01

    Small molecule drug discovery critically depends on the availability of meaningful in vitro assays to guide medicinal chemistry programs that are aimed at optimizing drug potency and selectivity. As it becomes increasingly evident, most disease relevant drug targets do not act as a single protein. In the body, they are instead generally found in complex with protein cofactors that are highly relevant for their correct function and regulation. This review highlights selected examples of the increasing trend to use biologically relevant protein complexes for rational drug discovery to reduce costly late phase attritions due to lack of efficacy or toxicity.

  17. 78 FR 32667 - Draft Guidance for Industry on Rheumatoid Arthritis: Developing Drug Products for Treatment...

    Science.gov (United States)

    2013-05-31

    ... products. This guidance revises the guidance for industry entitled ``Clinical Development Programs for... Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave... (HFM-40), Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville...

  18. Transporter-mediated natural product-drug interactions for the treatment of cardiovascular diseases.

    Science.gov (United States)

    Zha, Weibin

    2018-04-01

    The growing use of natural products in cardiovascular (CV) patients has been greatly raising the concerns about potential natural product-CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product-CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product-drug interactions. In last two decades, many CV drugs (e.g., angiotensin II receptor blockers, beta-blockers and statins) have been identified to be substrates and inhibitors of the solute carrier (SLC) transporters and the ATP-binding cassette (ABC) transporters, which are two major transporter superfamilies. Meanwhile, in vitro and in vivo studies indicate that a growing number of natural products showed cardioprotective effects (e.g., gingko biloba, danshen and their active ingredients) are also substrates and inhibitors of drug transporters. Thus, to understand transporter-mediated natural product-CV drug interactions is important and some transporter-mediated interactions have already shown to have clinical relevance. In this review, we review the current knowledge on the role of ABC and SLC transporters in CV therapy, as well as transporter modulation by natural products used in CV diseases and their induced natural product-CV drug interactions through alterations of drug transport. We hope our review will aid in a comprehensive summary of transporter-mediated natural product-CV drug interactions and help public and physicians understand these type of interactions. Copyright © 2017. Published by Elsevier B.V.

  19. Multi drug resistance and β-lactamase production by Klebsiella ...

    African Journals Online (AJOL)

    SERVER

    2007-08-06

    Aug 6, 2007 ... *Corresponding author. E-mail: gnsimha123@rediffmail.com. (Rice, 1999). plasmid that can be easily spread from one organisms to another (Sirot, 1995) these enzymes are capable of inactivating a variety of β-lactam drugs (Rice,. 1999). The ESBL producing organisms often show multi- drug resistant as ...

  20. 21 CFR 341.74 - Labeling of antitussive drug products.

    Science.gov (United States)

    2010-04-01

    ... directed by a doctor, if you have a breathing problem such as emphysema or chronic bronchitis, or if you... Section 341.74 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES..., consult a doctor.” (2) For oral and topical antitussives labeled for adults or for adults and children...

  1. Statin Drugs Markedly Inhibit Testosterone Production by Rat Leydig Cells In Vitro: Implications for Men

    Science.gov (United States)

    Statin drugs lower blood cholesterol by inhibiting hepatic 3-hydroxy-3-methylglutaryl-Coenzyme-A reductase. During drug development it was shown that statins inhibit production of cholesterol in the testis. We evaluated testosterone production in vitro, using highly purified rat ...

  2. 21 CFR 349.65 - Labeling of ophthalmic emollient drug products.

    Science.gov (United States)

    2010-04-01

    ... product contains the established name of the drug(s), if any, and identifies the product as a “lubricant... the eye or to exposure to wind or sun.” (3) “For use as a protectant against further irritation or to...

  3. 21 CFR 349.60 - Labeling of ophthalmic demulcent drug products.

    Science.gov (United States)

    2010-04-01

    ... product contains the established name of the drug(s), if any, and identifies the product as a “lubricant... exposure to wind or sun.” (3) “For use as a protectant against further irritation or to relieve dryness of...

  4. Product-line extensions and pricing strategies of brand-name drugs facing patent expiration.

    Science.gov (United States)

    Hong, Song Hee; Shepherd, Marvin D; Scoones, David; Wan, Thomas T H

    2005-01-01

    This study proposed an alternative to brand loyalty as the explanation for the continued price rigidity of patent-expired brand-name prescription drugs despite the increase in market entry of generic drugs facilitated by the 1984 Drug Price Competition and Patent Term Restoration Act. Study hypotheses were to test (1) whether market entries of new-product extensions are associated with market success of original brand-name drugs before generic drug entry, and (2) whether original brand-name drugs exhibit price rigidity to generic entry only when they are extended. The design is a retrospective follow-up study for the prescription drug brands that lost their patents between 1987 and 1992. The drug brands were limited to nonantibiotic, orally administered drugs containing only 1 active pharmaceutical ingredient. Information on patent expiration, entry of a product extension, and market success were determined from the U.S. Food and Drug Administration.s Orange Book, First DataBank, and American Druggist, respectively. Market success was defined as whether an original drug brand was listed in the top 100 prescriptions most frequently dispensed before facing generic entry. Product-line extension was defined as the appearance of another product that a company introduces within the same market after its existing product. Drug prices were average wholesale prices from the Drug Topics Red Book. The relationship between product-line extension and market success was examined using a logistic regression analysis. The price rigidity to entry was tested using a panel regression analysis. A total of 27 drug brands lost their patents between 1987 and 1992. Drug brands that achieved market success were 16 times more likely to be extended than were those that did not (OR=16, 95% confidence interval, 2.12-120.65). The price rigidity to entry existed in drug brands with extensions (beta=2.65%, P new product-line extension introduced for an original brand helps the original price be

  5. Optimization and modeling for the synthesis of sterol esters from deodorizer distillate by lipase-catalyzed esterification.

    Science.gov (United States)

    Zhang, Xinyu; Yu, Jiang; Zeng, Aiwu

    2017-03-01

    In this paper, cotton seed oil deodorizer distillate (CSODD), was recovered to obtain fatty acid sterol ester (FASE), which is one of the biological activated substances added as human therapeutic to lower cholesterol. Esterification reactions were carried out using Candida rugosa lipase as a catalyst, and the conversion of phytosterol was optimized using response surface methodology. The highest conversion (90.8 ± 0.4%) was reached at 0.84 wt% enzyme load, 1:25 solvent/CSODD mass ratio, and 44.2 °C after 12 H reaction. A kinetic model based on the reaction rate equation was developed to describe the reaction process. The activation energy of the reaction was calculated to be 56.9 kJ/mol and the derived kinetic parameters provided indispensable basics for further study. The optimization and kinetic research of synthesizing FASE from deodorizer distillate provided necessary information for the industrial applications in the near future. Experimental results showed that the proposed process is a promising alternative to recycle sterol esters from vegetable oil deodorizer distillates in a mild, efficient, and environmental friendly method. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

  6. Permanent Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products. Final rule.

    Science.gov (United States)

    2015-07-08

    The Food and Drug Administration (FDA or the Agency) is amending its regulations to implement certain drug shortages provisions of the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Food and Drug Administration Safety and Innovation Act (FDASIA). The rule requires all applicants of covered approved drugs or biological products--including certain applicants of blood or blood components for transfusion and all manufacturers of covered drugs marketed without an approved application--to notify FDA electronically of a permanent discontinuance or an interruption in manufacturing of the product that is likely to lead to a meaningful disruption in supply (or a significant disruption in supply for blood or blood components) of the product in the United States.

  7. Evaluating the Effects of Aluminum-Containing and Non-Aluminum Containing Deodorants on Axillary Skin Toxicity During Radiation Therapy for Breast Cancer: A 3-Armed Randomized Controlled Trial

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Lucy, E-mail: Lucy.lewis@curtin.edu.au [Centre for Nursing Research, Sir Charles Gairdner Hospital, Nedlands, Western Australia (Australia); School of Nursing and Midwifery Curtin University, Perth (Australia); Carson, Sharron [Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia (Australia); Bydder, Sean [Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia (Australia); School of Surgery, The University of Western Australia, Crawley, Western Australia (Australia); Athifa, Mariyam [School of Nursing and Midwifery Curtin University, Perth (Australia); Williams, Anne M. [School of Nursing and Midwifery Curtin University, Perth (Australia); School of Nursing and Midwifery, Edith Cowan University, Perth, Western Australia (Australia); Bremner, Alexandra [School of Population Health, The University of Western Australia, Crawley, Western Australia (Australia)

    2014-11-15

    Purpose: Deodorant use during radiation therapy for breast cancer has been controversial as there are concerns deodorant use may exacerbate axillary skin toxicity. The present study prospectively determined the use of both aluminum-containing and non aluminum containing deodorants on axillary skin toxicity during conventionally fractionated postoperative radiation therapy for breast cancer. Methods and Materials: This 3-arm randomized controlled study was conducted at a single center, tertiary cancer hospital between March 2011 and April 2013. Participants were randomized to 1 of 2 experimental groups (aluminum-containing deodorant and soap or non–aluminum containing deodorant and soap) or a control group (soap). A total of 333 participants were randomized. Generalized estimating equations were used to estimate and compare the odds of experiencing high levels of sweating and skin toxicity in each of the deodorant groups to the odds in the control group. The study evaluated a range of endpoints including objective measurements of axilla sweating, skin toxicity, pain, itch and burning. Quality of life was assessed with a validated questionnaire. Results: Radiation characteristics were similar across all groups. Patients in the deodorant groups did not report significantly different ratings for axillary pain, itch, or burning compared with the control group. Patients in the aluminum-containing deodorant group experienced significantly less sweating than the control; the odds of their sweating being barely tolerable and frequently or always interfering with their daily activities was decreased by 85% (odds ratio, 0.15; 95% confidence interval, 0.03-0.91). Conclusions: We found no evidence that the use of either aluminum-containing or non–aluminum containing deodorant adversely effects axillary skin reaction during conventionally fractionated radiation therapy for breast cancer. Our analysis also suggests patients in the aluminum-containing deodorant arm had

  8. Evaluating the Effects of Aluminum-Containing and Non-Aluminum Containing Deodorants on Axillary Skin Toxicity During Radiation Therapy for Breast Cancer: A 3-Armed Randomized Controlled Trial

    International Nuclear Information System (INIS)

    Lewis, Lucy; Carson, Sharron; Bydder, Sean; Athifa, Mariyam; Williams, Anne M.; Bremner, Alexandra

    2014-01-01

    Purpose: Deodorant use during radiation therapy for breast cancer has been controversial as there are concerns deodorant use may exacerbate axillary skin toxicity. The present study prospectively determined the use of both aluminum-containing and non aluminum containing deodorants on axillary skin toxicity during conventionally fractionated postoperative radiation therapy for breast cancer. Methods and Materials: This 3-arm randomized controlled study was conducted at a single center, tertiary cancer hospital between March 2011 and April 2013. Participants were randomized to 1 of 2 experimental groups (aluminum-containing deodorant and soap or non–aluminum containing deodorant and soap) or a control group (soap). A total of 333 participants were randomized. Generalized estimating equations were used to estimate and compare the odds of experiencing high levels of sweating and skin toxicity in each of the deodorant groups to the odds in the control group. The study evaluated a range of endpoints including objective measurements of axilla sweating, skin toxicity, pain, itch and burning. Quality of life was assessed with a validated questionnaire. Results: Radiation characteristics were similar across all groups. Patients in the deodorant groups did not report significantly different ratings for axillary pain, itch, or burning compared with the control group. Patients in the aluminum-containing deodorant group experienced significantly less sweating than the control; the odds of their sweating being barely tolerable and frequently or always interfering with their daily activities was decreased by 85% (odds ratio, 0.15; 95% confidence interval, 0.03-0.91). Conclusions: We found no evidence that the use of either aluminum-containing or non–aluminum containing deodorant adversely effects axillary skin reaction during conventionally fractionated radiation therapy for breast cancer. Our analysis also suggests patients in the aluminum-containing deodorant arm had

  9. Equivalence of complex drug products: advances in and challenges for current regulatory frameworks.

    Science.gov (United States)

    Hussaarts, Leonie; Mühlebach, Stefan; Shah, Vinod P; McNeil, Scott; Borchard, Gerrit; Flühmann, Beat; Weinstein, Vera; Neervannan, Sesha; Griffiths, Elwyn; Jiang, Wenlei; Wolff-Holz, Elena; Crommelin, Daan J A; de Vlieger, Jon S B

    2017-11-01

    Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow-on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow-on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow-up were identified: (1) assessment of critical attributes to establish equivalence for follow-on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

  10. 21 CFR 328.50 - Principal display panel of all OTC drug products intended for oral ingestion that contain alcohol.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Principal display panel of all OTC drug products intended for oral ingestion that contain alcohol. 328.50 Section 328.50 Food and Drugs FOOD AND DRUG... PRODUCTS INTENDED FOR ORAL INGESTION THAT CONTAIN ALCOHOL Labeling § 328.50 Principal display panel of all...

  11. 21 CFR 212.70 - What controls and acceptance criteria must I have for my finished PET drug products?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What controls and acceptance criteria must I have... POSITRON EMISSION TOMOGRAPHY DRUGS (Eff. 12-12-2011) Finished Drug Product Controls and Acceptance § 212.70 What controls and acceptance criteria must I have for my finished PET drug products? (a) Specifications...

  12. 21 CFR 310.528 - Drug products containing active ingredients offered over-the-counter (OTC) for use as an...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Drug products containing active ingredients offered over-the-counter (OTC) for use as an aphrodisiac. 310.528 Section 310.528 Food and Drugs FOOD AND... drug product. Anise, cantharides, don qual, estrogens, fennel, ginseng, golden seal, gotu kola, Korean...

  13. The Product Quality Research Institute (PQRI) Leachables and Extractables Working Group Initiatives for Parenteral and Ophthalmic Drug Product (PODP).

    Science.gov (United States)

    Paskiet, Diane; Jenke, Dennis; Ball, Douglas; Houston, Christopher; Norwood, Daniel L; Markovic, Ingrid

    2013-01-01

    The Product Quality Research Institute (PQRI) is a non-profit consortium of organizations working together to generate and share timely, relevant, and impactful information that advances drug product quality and development. The collaborative activities of PQRI participants have, in the case of orally inhaled and nasal drug products (OINDPs), resulted in comprehensive and widely-accepted recommendations for leachables assessments to help ensure patient safety with respect to this class of packaged drug products. These recommendations, which include scientifically justified safety thresholds for leachables, represent a significant milestone towards establishing standardized approaches for safety qualification of leachables in OINDP. To build on the success of the OINDP effort, PQRI's Parenteral and Ophthalmic Drug Products (PODP) Leachables and Extractables Working Group was formed to extrapolate the OINDP threshold concepts and best practice recommendations to other dosage forms with high concern for interaction with packaging/delivery systems. This article considers the general aspects of leachables and their safety assessment, introduces the PODP Work Plan and initial study Protocol, discusses the laboratory studies being conducted by the PODP Chemistry Team, outlines the strategy being developed by the PODP Toxicology Team for the safety qualification of PODP leachables, and considers the issues associated with application of the safety thresholds, particularly with respect to large-volume parenterals. Lastly, the unique leachables issues associated with biologics are described. The Product Quality Research Institute (PQRI) is a non-profit consortium involving industry organizations, academia, and regulatory agencies that together provide recommendations in support of regulatory guidance to advance drug product quality. The collaborative activities of the PQRI Orally Inhaled and Nasal Drug Products Leachables and Extractables Working Group resulted in a

  14. Production and Investigation of Controlled Drug Release Properties of Tamoxifen Loaded Alginate-Gum Arabic Microbeads

    Directory of Open Access Journals (Sweden)

    Rukiye Yavaşer

    2016-08-01

    Full Text Available The entrapment of tamoxifen onto alginate-gum arabic beads and the production of controlled drug release was investigated in this study. The polymeric system that would provide the controlled release of tamoxifen was formed using alginate and gum arabic. In the first phase of the study, the optimization of the alginate-gum arabic beads production was conducted; then the study continued with drug entrapment experiments. Tamoxifen entrapment yield was found to be approximately 90% of initial tamoxifen concentration. In vitro drug release experiments were performed in simulated gastric juice and intestinal fluid where the tamoxifen release was 20% and 53% of the initial drug present, respectively. As a result of this study, it is expected that a valuable contribution to the field of controlled drug release system production is realized.

  15. 21 CFR 310.530 - Topically applied hormone-containing drug products for over-the-counter (OTC) human use.

    Science.gov (United States)

    2010-04-01

    ... labeling or in the ingredient statement is an implied drug claim. The claim implied by the use of this term... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Topically applied hormone-containing drug products for over-the-counter (OTC) human use. 310.530 Section 310.530 Food and Drugs FOOD AND DRUG...

  16. 21 CFR 212.80 - What are the requirements associated with labeling and packaging PET drug products?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What are the requirements associated with labeling and packaging PET drug products? 212.80 Section 212.80 Food and Drugs FOOD AND DRUG ADMINISTRATION... POSITRON EMISSION TOMOGRAPHY DRUGS (Eff. 12-12-2011) Packaging and Labeling § 212.80 What are the...

  17. [Adverse muscle effects of a podofyllotoxin-containing cytotoxic drug product with simvastatin].

    Science.gov (United States)

    Kaipiainen-Seppänen, Oili; Savolainen, Elina; Elfving, Pia; Kononoff, Aulikki

    2009-01-01

    With the ageing population, drug interactions pose an increasing challenge to health professionals. We describe four patients, for whom concurrent administration of a podofyllotoxin-containing cytotoxic drug product and simvastatin caused severe adverse effects on muscles, including muscle pain, soreness or fatigue or weakness, and in some patients also disintegration of muscle tissue, i.e. rhabdomyolysis. The metabolism of both drugs proceeds via the common CYP3A4 enzyme pathway.

  18. 78 FR 38053 - Determination That OPANA ER (Oxymorphone Hydrochloride) Drug Products Covered by New Drug...

    Science.gov (United States)

    2013-06-25

    ... marketing for reasons other than safety or effectiveness. FDA will not begin procedures to withdraw approval... Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug...-610 were not withdrawn from sale for reasons of safety or effectiveness. This determination means that...

  19. Evaluation of In-Use Stability of Anticoagulant Drug Products: Warfarin Sodium.

    Science.gov (United States)

    Nguyenpho, Agnes; Ciavarella, Anthony B; Siddiqui, Akhtar; Rahman, Ziyaur; Akhtar, Sohail; Hunt, Robert; Korang-Yeboah, Maxwell; Khan, Mansoor A

    2015-12-01

    The objective of the study was to evaluate the stability of warfarin products during use by patients or caregivers. For evaluation, three commercial products manufactured by different processes were selected and placed at 30°C/75%RH to simulate in use condition. Samples were withdrawn up to 12 weeks and analyzed for the physicochemical changes. Scanning electron microscopy demonstrated increasing holes and craters in the tablets over the timeframe. Near-infrared chemical imaging and powder X-ray powder diffraction corroborated the change arising from conversion of crystalline to amorphous forms of the drug. Hardness and disintegration time of the tablets were found to increase progressively. With increasing time, moisture contents of the products were found to increase and consequent decrease in isopropyl alcohol content of the product. Dissolution of the tablets in media at pH 4.5 demonstrated discrimination between crystalline and amorphous drug products. Overall, percent drug dissolved in each product at 30 min was found to decrease with increasing exposure time. Dissolution of drug decreased from 54% to 38% and 82% to 54% for the two products while the third product maintained consistently high level of dissolution. These results suggest that the drug product quality attributes can change during use. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  20. Use of drugs and antibiotics in poultry production in Ghana | Turkson ...

    African Journals Online (AJOL)

    This study was designed to assess the extent of drug and antibiotic use in small and large commercial poultry producers in Ghana, and the extent of the knowledge, perceptions and practice of drug withdrawal period in poultry production. In all, 483 poultry farmers in Greater Accra, Ashanti and Central regions were ...

  1. 21 CFR 338.50 - Labeling of nighttime sleep-aid drug products.

    Science.gov (United States)

    2010-04-01

    ... for more than 2 weeks, consult your doctor. Insomnia may be a symptom of serious underlying medical illness.” (3) “Do not take this product, unless directed by a doctor, if you have a breathing problem such....50 Section 338.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  2. 75 FR 48352 - Determination That MOTRIN (Ibuprofen) Tablets and Four Other Drug Products Were Not Withdrawn...

    Science.gov (United States)

    2010-08-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0391] Determination That MOTRIN (Ibuprofen) Tablets and Four Other Drug Products Were Not Withdrawn From Sale for... Applicant NDA 17-463 MOTRIN (ibuprofen) Tablets, 300 milligrams (mg), McNeil Consumer Healthcare, 7050 Camp...

  3. 77 FR 12311 - Guidance for Industry on Size of Beads in Drug Products Labeled for Sprinkle; Availability

    Science.gov (United States)

    2012-02-29

    ...] Guidance for Industry on Size of Beads in Drug Products Labeled for Sprinkle; Availability AGENCY: Food and... the availability of a guidance for industry entitled ``Size of Beads in Drug Products Labeled for... Evaluation and Research's (CDER's) current thinking on appropriate size ranges for beads in drug products...

  4. 76 FR 3144 - Draft Guidance for Industry on Size of Beads in Drug Products Labeled for Sprinkle; Availability

    Science.gov (United States)

    2011-01-19

    ...] Draft Guidance for Industry on Size of Beads in Drug Products Labeled for Sprinkle; Availability AGENCY... announcing the availability of a draft guidance for industry entitled ``Size of Beads in Drug Products... Evaluation and Research's (CDER's) current thinking on appropriate size ranges for beads in drug products...

  5. CH3SH adsorption properties and mechanism of deodorant filter made of iron hydroxide on porous iron frame; Tetsu takotaisei dasshu filter no methyl mercaptan jokyo seino to jokyo kiko

    Energy Technology Data Exchange (ETDEWEB)

    Noda, T. [Nippon Steel Corp., Tokyo (Japan)

    1998-05-10

    It is suggested that methyl mercaptan is decomposed to methyl sulfide and hydrogen by reaction with the a-iron hydroxide, and then the methyl sulfide combines with sulfur crystal and the hydrogen changes into water by the chemical reaction with the {alpha}-iron hydroxide. A deodorant filter was made by treating porous metallic iron with an aqueous solution of L-ascorbic acid, iron (II) sulfate and calcium hydroxide aqueous solution to deposit the iron ascorbate and the {alpha}-iron hydroxide on it. Then the deodorant filter was exposed to the hydrogen sulfide to yield the sulfur crystals on the surface of the deodorant filter. The methyl mercaptan removal capacity of the deodorant filter was studied with repetition of removal tests. Results show that the methyl mercaptan removal capacity of the deodorant filter is a little smaller than that of conventional granular activated carbon. 6 refs., 6 figs., 3 tabs.

  6. Ammonia adsorption properties and its mechanism of deodorant filter made of iron ascorbate on porous iron frame; Tetsu takotai, asukorubin san dasshu filter no ammonia dasshu kiko

    Energy Technology Data Exchange (ETDEWEB)

    Noda, T.; Kanamaru, T.; Maeda, S. [Nippon Steel Corp., Tokyo (Japan)

    1996-07-10

    A deodorant filter was made by treating porous metallic iron with an L-ascorbic acid aqueous solutions depositing the iron ascorbate on it. The ammonia adsorption capacity of the deodorant filter was studied with repetitive runs of adsorption tests. The results show that the ammonia adsorption capacity of the iron ascorbate is nearly equal to conventions: granular activated carbon at the beginning, but unlike the letter, the iron ascorbate perfectly recovers the capacity via reversible desorption. ESR and Mossbauer spectroscopy reveal that ammonia goes into the inner coordination sphere of Fe(II) and Fe(III), capable of reversible adsorption and desorption, and that the reactivity of iron is attributable to the formation of the ascorbate complex, which is formed in the specific manufacturing process of the deodorant filter. 13 refs., 7 figs., 1 tab.

  7. Overview of Skin Whitening Agents: Drugs and Cosmetic Products

    Directory of Open Access Journals (Sweden)

    Céline Couteau

    2016-07-01

    Full Text Available Depigmentation and skin lightening products, which have been in use for ages in Asian countries where skin whiteness is a major esthetic criterion, are now also highly valued by Western populations, who expose themselves excessively to the sun and develop skin spots as a consequence. After discussing the various possible mechanisms of depigmentation, the different molecules that can be used as well as the status of the products containing them will now be presented. Hydroquinone and derivatives thereof, retinoids, alpha- and beta-hydroxy acids, ascorbic acid, divalent ion chelators, kojic acid, azelaic acid, as well as diverse herbal extracts are described in terms of their efficacy and safety. Since a genuine effect (without toxic effects is difficult to obtain, prevention by using sunscreen products is always preferable.

  8. 21 CFR 352.52 - Labeling of sunscreen drug products.

    Science.gov (United States)

    2010-04-01

    ... sunburn [bullet] higher SPF gives more sunburn protection”. 1 See § 201.66(b)(4) of this chapter. (ii) For... “minimum”) “protection against” (select one of the following: “sunburn” or “sunburn and tanning”)], or “[bullet] for skin that sunburns minimally”. (ii) For products that provide an SPF of 12 to under 30...

  9. 21 CFR 357.150 - Labeling of anthelmintic drug products.

    Science.gov (United States)

    2010-04-01

    ... “pinworm treatment.” (b) Indication. The labeling of the product states, under the heading “Indication,” the following: “For the treatment of pinworms.” Other truthful and nonmisleading statements... repeat treatment unless directed by a doctor. When one individual in a household has pinworms, the entire...

  10. 21 CFR 349.78 - Labeling of eyewash drug products.

    Science.gov (United States)

    2010-04-01

    ...,” “air pollutants (smog or pollen),” or “chlorinated water”). (2) “For” (select one of the following...),” or “chlorinated water”). (c) Warnings. In addition to the warnings in § 349.50, the labeling of the... products intended for use with an eyecup. Rinse cup with clean water immediately before each use. Avoid...

  11. Production of biological nanoparticles from Θ- lactalbumin for drug ...

    African Journals Online (AJOL)

    In recent years, the concept of controlled release of encapsulated ingredients at the right place and the right time has become of more interest to the food and pharmaceutical industry. Whey proteins are valuable by-products from the cheese industry. The physicochemical properties of the whey proteins suggest that they ...

  12. Drug-enhanced carbon monoxide production from heme by cytochrome P450 reductase

    Directory of Open Access Journals (Sweden)

    Dragic Vukomanovic

    2017-01-01

    Full Text Available Carbon monoxide (CO formed endogenously is considered to be cytoprotective, and the vast majority of CO formation is attributed to the degradation of heme by heme oxygenases-1 and -2 (HO-1, HO-2. Previously, we observed that brain microsomes containing HO-2 produced many-fold more CO in the presence of menadione and its congeners; herein we explored these observations further. We determined the effects of various drugs on CO production of rat brain microsomes and recombinant human cytochrome P450 reductase (CPR; CO was measured by gas chromatography with reductive detection. Brain microsomes of Sprague-Dawley rats or recombinant human cytochrome P450 reductase (CPR were incubated with NADPH and various drugs in closed vials in phosphate buffer at pH 7.4 and 37°C. After 15 minutes, the reaction was stopped by cooling in dry ice, and the headspace gas was analyzed for CO production using gas chromatography with reductive (mercuric oxide detection. We observed drug-enhanced CO production in the presence of both microsomes and recombinant CPR alone; the presence of HO was not required. A range of structurally diverse drugs were capable of amplifying this CO formation; these molecules had structures consistent with redox cycling capability. The addition of catalase to a reaction mixture, that contained activating drugs, inhibited the production of CO. Drug-enhanced CO formation can be catalyzed by CPR. The mechanism of CPR activation was not through classical drug-receptor mediation. Redox cycling may be involved in the drug-induced amplification of CO production by CPR through the production of reactive oxygen species.

  13. Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development.

    Science.gov (United States)

    Li, Min; Sander, Sanna; Duan, John; Rosencrance, Susan; Miksinski, Sarah Pope; Yu, Lawrence; Seo, Paul; Rege, Bhagwant

    2016-11-01

    This review presents scientific and regulatory considerations for the development of solid oral modified release (MR) drug products. It includes a rationale for patient-focused development based on Quality-by-Design (QbD) principles. Product and process understanding of MR products includes identification and risk-based evaluation of critical material attributes (CMAs), critical process parameters (CPPs), and their impact on critical quality attributes (CQAs) that affect the clinical performance. The use of various biopharmaceutics tools that link the CQAs to a predictable and reproducible clinical performance for patient benefit is emphasized. Product and process understanding lead to a more comprehensive control strategy that can maintain product quality through the shelf life and the lifecycle of the drug product. The overall goal is to develop MR products that consistently meet the clinical objectives while mitigating the risks to patients by reducing the probability and increasing the detectability of CQA failures.

  14. 21 CFR 211.110 - Sampling and testing of in-process materials and drug products.

    Science.gov (United States)

    2010-04-01

    ... PHARMACEUTICALS Production and Process Controls § 211.110 Sampling and testing of in-process materials and drug... capsule weight variation; (2) Disintegration time; (3) Adequacy of mixing to assure uniformity and... production process, e.g., at commencement or completion of significant phases or after storage for long...

  15. Synthetic and bioengineered products in nuclear medicine and drug delivery

    International Nuclear Information System (INIS)

    Frier, M.

    1997-01-01

    Full text. The supply of radio pharmaceuticals based on pooled human blood products, for example human serum albumin (H S A) and fibrinogen, has previously met with some problems due to the possibility of donor infection A common feature of all biologicals of animal or human origin is the potential risk of viral contamination from the source material. Recombinant DNA technology provides an alternative source of biological materials that have applications throughout medicine. Micro capsules prepared from recombinant human serum albumin (r H S A) are currently under development as ultrasound contrast agents. Similar products would serve as an alternative source of material to serum albumin pooled from human donors and would offer great potential in the production of radio pharmaceuticals. There is a growing interest in the use of macromolecular carriers for therapeutic agents. When labelled with and appropriate gamma-emitter, their biodistribution can be be followed by scintigraphy. The biodistribution of a synthetic branched polypeptide, based on a poly-L-lysine backbone (average molecular mass 45 kDa) is described. The polymer was conjugated to diethylene triamine penta-acetic acid and labelled by chelation with Indium-111. Mice were injected i.v. with labelled material and imaged with a gamma camera with a pin hole collimator. Images showed the majority of tracer remaining in the blood poll, but about 35% appeared in the urinary bladder within 1.5 h

  16. Investigation of drug products received for analysis in the Swedish STRIDA project on new psychoactive substances.

    Science.gov (United States)

    Bäckberg, Matilda; Jönsson, Karl-Henrik; Beck, Olof; Helander, Anders

    2018-02-01

    The web-based open sale of unregulated new psychoactive substances (NPS) has shown a steady increase in recent years. Analysis of drug products sold as NPS is useful to confirm the true chemical contents, for comparison with the substances detected in corresponding body fluids, but also to study drug trends. This work describes the examination of 251 drug products that were randomly submitted for analysis in 173 cases of suspected NPS-related intoxications in the Swedish STRIDA project in 2010-2015. Of the products, 39% were powders/crystals, 32% tablets/capsules, 16% herbal materials, 8% liquids, 1% blotters, and 4% others. The analysis involved tandem mass spectrometry and nuclear magnetic resonance spectroscopy. In 88 products (35%), classic psychoactive substances, prescription pharmaceuticals, dietary supplements, or doping agents were found; however, in none of these cases had an NPS-related intoxication been indicated from product markings or patient self-reports. Another 12 products tested negative for psychoactive substances. The remaining 151 products contained 86 different NPS (30% contained ≥2 substances). In 104 drug products, a specific NPS ingredient was indicated based on labelling (69%) or patient self-report; in 92 cases this was also analytically confirmed to be correct. Overall, the NPS products submitted for analysis in the STRIDA project showed a high degree of consistency between suspected and actual content (88%). The results of related urine and/or blood analysis further demonstrated that the patients commonly (89%) tested positive for the indicated NPS, but also revealed that polysubstance intoxication was common (83%), indicating use of additional drug products. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Sample preparation composite and replicate strategy for assay of solid oral drug products.

    Science.gov (United States)

    Harrington, Brent; Nickerson, Beverly; Guo, Michele Xuemei; Barber, Marc; Giamalva, David; Lee, Carlos; Scrivens, Garry

    2014-12-16

    In pharmaceutical analysis, the results of drug product assay testing are used to make decisions regarding the quality, efficacy, and stability of the drug product. In order to make sound risk-based decisions concerning drug product potency, an understanding of the uncertainty of the reportable assay value is required. Utilizing the most restrictive criteria in current regulatory documentation, a maximum variability attributed to method repeatability is defined for a drug product potency assay. A sampling strategy that reduces the repeatability component of the assay variability below this predefined maximum is demonstrated. The sampling strategy consists of determining the number of dosage units (k) to be prepared in a composite sample of which there may be a number of equivalent replicate (r) sample preparations. The variability, as measured by the standard error (SE), of a potency assay consists of several sources such as sample preparation and dosage unit variability. A sampling scheme that increases the number of sample preparations (r) and/or number of dosage units (k) per sample preparation will reduce the assay variability and thus decrease the uncertainty around decisions made concerning the potency of the drug product. A maximum allowable repeatability component of the standard error (SE) for the potency assay is derived using material in current regulatory documents. A table of solutions for the number of dosage units per sample preparation (r) and number of replicate sample preparations (k) is presented for any ratio of sample preparation and dosage unit variability.

  18. A new roadmap for biopharmaceutical drug product development: Integrating development, validation, and quality by design.

    Science.gov (United States)

    Martin-Moe, Sheryl; Lim, Fredric J; Wong, Rita L; Sreedhara, Alavattam; Sundaram, Jagannathan; Sane, Samir U

    2011-08-01

    Quality by design (QbD) is a science- and risk-based approach to drug product development. Although pharmaceutical companies have historically used many of the same principles during development, this knowledge was not always formally captured or proactively submitted to regulators. In recent years, the US Food and Drug Administration has also recognized the need for more controls in the drug manufacturing processes, especially for biological therapeutics, and it has recently launched an initiative for Pharmaceutical Quality for the 21st Century to modernize pharmaceutical manufacturing and improve product quality. In the biopharmaceutical world, the QbD efforts have been mainly focused on active pharmaceutical ingredient processes with little emphasis on drug product development. We present a systematic approach to biopharmaceutical drug product development using a monoclonal antibody as an example. The approach presented herein leverages scientific understanding of products and processes, risk assessments, and rational experimental design to deliver processes that are consistent with QbD philosophy without excessive incremental effort. Data generated using these approaches will not only strengthen data packages to support specifications and manufacturing ranges but hopefully simplify implementation of postapproval changes. We anticipate that this approach will positively impact cost for companies, regulatory agencies, and patients, alike. Copyright © 2011 Wiley-Liss, Inc.

  19. 78 FR 72840 - Drug Products That Present Demonstrable Difficulties for Compounding Under Sections 503A and 503B...

    Science.gov (United States)

    2013-12-04

    ... reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product'' (section 503A... because it included restrictions on the advertising or promotion of the compounding of any particular drug... effect on the safety or effectiveness of that drug product. In addition, the DQSA adds a new section 503B...

  20. 21 CFR 358.750 - Labeling of drug products for the control of dandruff, seborrheic dermatitis, or psoriasis.

    Science.gov (United States)

    2010-04-01

    ... dandruff, seborrheic dermatitis, or psoriasis. 358.750 Section 358.750 Food and Drugs FOOD AND DRUG... Dermatitis, and Psoriasis § 358.750 Labeling of drug products for the control of dandruff, seborrheic dermatitis, or psoriasis. (a) Statement of identity. The labeling of the product contains the established...

  1. 21 CFR 310.548 - Drug products containing colloidal silver ingredients or silver salts offered over-the-counter...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Drug products containing colloidal silver... Drug products containing colloidal silver ingredients or silver salts offered over-the-counter (OTC) for the treatment and/or prevention of disease. (a) Colloidal silver ingredients and silver salts have...

  2. Microvesicle formulations used in topical drugs and cosmetics affect product efficiency, performance and allergenicity

    DEFF Research Database (Denmark)

    Madsen, Jakob Torp; Ejner Andersen, Klaus

    2010-01-01

    transdermal delivery more efficient for a number of drugs. Vesicular systems may also allow a more precise drug delivery to the site of action (ie, the hair follicles) and thereby minimize the applied drug concentration, reducing potential side effects. On the other hand, this may increase the risk of other......Attempts to improve the formulations of topical products are continuing processes (ie, to increase cosmetic performance, enhance effects, and protect ingredients from degradation). The development of micro- and nanovesicular systems has led to the marketing of topical drugs and cosmetics that use...... these technologies. Several articles have reported improved clinical efficacy by the encapsulation of pharmaceuticals in vesicular systems, and the numbers of publications and patents are rising. Some vesicular systems may deliver the drug deeper in the skin as compared to conventional vehicles, or even make...

  3. Stability of Reconstituted Telavancin Drug Product in Frozen Intravenous Bags.

    Science.gov (United States)

    Gu, Zhengtian; Wong, Anissa; Raquinio, Elvira; Nguyen, Alice

    2015-07-01

    Intravenous (IV) infusions of telavancin for injection are generally administered in-hospital, but in some circumstances they may be administered in an outpatient environment. In that setting, antibiotics may be premixed and frozen. This study determined the chemical stability of nonpreserved telavancin in various commonly used reconstitution diluents stored in IV bags (polyvinyl chloride [PVC] and PVC-free) at -20°C (-4°F) without light. Telavancin (750 mg/vial) was reconstituted with 5% dextrose injection USP (D5W) or 0.9% sodium chloride injection USP (NS) to obtain drug solutions at approximately 15 mg/mL. Infusion solutions of telavancin at diluted concentrations of 0.6 mg/mL and 8.0 mg/mL covering the range utilized in clinical practice were prepared in both PVC and PVC-free IV bags using D5W or NS solutions. The infusion solutions were stored under frozen conditions (-20°C ± 5°C [-4°F ± 41°F]) and the chemical stability was evaluated for up to 32 days. Telavancin concentration, purity, and degradant levels were determined using a stability-indicating high-performance liquid chromatography (HPLC) method. Telavancin IV infusion solutions in D5W or NS at 0.6 mg/mL and 8 mg/mL and stored at -20°C (-4°F) met the chemical stability criteria when tested on days 0, 7, 14, and 32. The assayed telavancin concentration at each time point was within 97% to 103% of the initial mean assay value. The total degradants quantified by the HPLC stability-indicating method did not show any significant change over the 32-day study period. Telavancin IV infusion solutions (in D5W or NS) in both PVC and PVC-free IV bags were stable for at least 32 days when stored at -20°C (-4°F) without light. These results provide prolonged frozen stability data further to that previously established for 7 days under refrigerated conditions (2°C-8°C [36°F -46°F]), and for 12 hours at room temperature when diluted into IV bags containing D5W, NS, or lactated Ringer's solution.

  4. Ethnic hair care products may increase false positives in hair drug testing.

    Science.gov (United States)

    Kidwell, David A; Smith, Frederick P; Shepherd, Arica R

    2015-12-01

    The question of why different races appear more susceptible to hair contamination by external drugs remains controversial. This research studied susceptibility of head hair to external cocaine and methamphetamine when hair products have been applied. Three different chemical classes of ethnic hair products were applied to Caucasian, Asian, and African hair. Some products increased the methamphetamine and cocaine concentrations in all hair types. A unique finding of this research is that certain ethnic hair products can replace moisture as a diffusion medium, thereby increasing the susceptibility to contamination over 100-fold compared to petroleum-based products. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Harnessing the potential of natural products in drug discovery from a cheminformatics vantage point.

    Science.gov (United States)

    Rodrigues, Tiago

    2017-11-15

    Natural products (NPs) present a privileged source of inspiration for chemical probe and drug design. Despite the biological pre-validation of the underlying molecular architectures and their relevance in drug discovery, the poor accessibility to NPs, complexity of the synthetic routes and scarce knowledge of their macromolecular counterparts in phenotypic screens still hinder their broader exploration. Cheminformatics algorithms now provide a powerful means of circumventing the abovementioned challenges and unlocking the full potential of NPs in a drug discovery context. Herein, I discuss recent advances in the computer-assisted design of NP mimics and how artificial intelligence may accelerate future NP-inspired molecular medicine.

  6. Combinative Particle Size Reduction Technologies for the Production of Drug Nanocrystals

    Directory of Open Access Journals (Sweden)

    Jaime Salazar

    2014-01-01

    Full Text Available Nanosizing is a suitable method to enhance the dissolution rate and therefore the bioavailability of poorly soluble drugs. The success of the particle size reduction processes depends on critical factors such as the employed technology, equipment, and drug physicochemical properties. High pressure homogenization and wet bead milling are standard comminution techniques that have been already employed to successfully formulate poorly soluble drugs and bring them to market. However, these techniques have limitations in their particle size reduction performance, such as long production times and the necessity of employing a micronized drug as the starting material. This review article discusses the development of combinative methods, such as the NANOEDGE, H 96, H 69, H 42, and CT technologies. These processes were developed to improve the particle size reduction effectiveness of the standard techniques. These novel technologies can combine bottom-up and/or top-down techniques in a two-step process. The combinative processes lead in general to improved particle size reduction effectiveness. Faster production of drug nanocrystals and smaller final mean particle sizes are among the main advantages. The combinative particle size reduction technologies are very useful formulation tools, and they will continue acquiring importance for the production of drug nanocrystals.

  7. Water Filtration Products

    Science.gov (United States)

    1986-01-01

    American Water Corporation manufactures water filtration products which incorporate technology originally developed for manned space operations. The formula involves granular activated charcoal and other ingredients, and removes substances by catalytic reactions, mechanical filtration, and absorption. Details are proprietary. A NASA literature search contributed to development of the compound. The technology is being extended to a deodorizing compound called Biofresh which traps gas and moisture inside the unit. Further applications are anticipated.

  8. Transit and lifespan in neutrophil production: implications for drug intervention.

    Science.gov (United States)

    Câmara De Souza, Daniel; Craig, Morgan; Cassidy, Tyler; Li, Jun; Nekka, Fahima; Bélair, Jacques; Humphries, Antony R

    2018-02-01

    A comparison of the transit compartment ordinary differential equation modelling approach to distributed and discrete delay differential equation models is studied by focusing on Quartino's extension to the Friberg transit compartment model of myelosuppression, widely relied upon in the pharmaceutical sciences to predict the neutrophil response after chemotherapy, and on a QSP delay differential equation model of granulopoiesis. An extension to the Quartino model is provided by considering a general number of transit compartments and introducing an extra parameter that allows for the decoupling of the maturation time from the production rate of cells. An overview of the well established linear chain technique, used to reformulate transit compartment models with constant transit rates as distributed delay differential equations (DDEs), is then given. A state-dependent time rescaling of the Quartino model is performed to apply the linear chain technique and rewrite the Quartino model as a distributed DDE, yielding a discrete DDE model in a certain parameter limit. Next, stability and bifurcation analyses are undertaken in an effort to situate such studies in a mathematical pharmacology context. We show that both the original Friberg and the Quartino extension models incorrectly define the mean maturation time, essentially treating the proliferative pool as an additional maturation compartment. This misspecification can have far reaching consequences on the development of future models of myelosuppression in PK/PD.

  9. Plants’ Natural Products as Alternative Promising Anti-Candida Drugs

    Science.gov (United States)

    Soliman, Sameh; Alnajdy, Dina; El-Keblawy, Ali A.; Mosa, Kareem A.; Khoder, Ghalia; Noreddin, Ayman M.

    2017-01-01

    Candida is a serious life-threatening pathogen, particularly with immunocompromised patients. Candida infections are considered as a major cause of morbidity and mortality in a broad range of immunocompromised patients. Candida infections are common in hospitalized patients and elderly people. The difficulty to eradicate Candida infections is owing to its unique switch between yeast and hyphae forms and more likely to biofilm formations that render resistance to antifungal therapy. Plants are known sources of natural medicines. Several plants show significant anti-Candida activities and some of them have lower minimum inhibitory concentration, making them promising candidates for anti-Candida therapy. However, none of these plant products is marketed for anti-Candida therapy because of lack of sufficient information about their efficacy, toxicity, and kinetics. This review revises major plants that have been tested for anti-Candida activities with recommendations for further use of some of these plants for more investigation and in vivo testing including the use of nanostructure lipid system. PMID:28989245

  10. Sample preparation composite and replicate strategy case studies for assay of solid oral drug products.

    Science.gov (United States)

    Nickerson, Beverly; Harrington, Brent; Li, Fasheng; Guo, Michele Xuemei

    2017-11-30

    Drug product assay is one of several tests required for new drug products to ensure the quality of the product at release and throughout the life cycle of the product. Drug product assay testing is typically performed by preparing a composite sample of multiple dosage units to obtain an assay value representative of the batch. In some cases replicate composite samples may be prepared and the reportable assay value is the average value of all the replicates. In previously published work by Harrington et al. (2014) [5], a sample preparation composite and replicate strategy for assay was developed to provide a systematic approach which accounts for variability due to the analytical method and dosage form with a standard error of the potency assay criteria based on compendia and regulatory requirements. In this work, this sample preparation composite and replicate strategy for assay is applied to several case studies to demonstrate the utility of this approach and its application at various stages of pharmaceutical drug product development. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Differences in rates of switchbacks after switching from branded to authorized generic and branded to generic drug products: cohort study

    Science.gov (United States)

    Sarpatwari, Ameet; Dejene, Sara; Khan, Nazleen F; Lii, Joyce; Rogers, James R; Dutcher, Sarah K; Raofi, Saeid; Bohn, Justin; Connolly, John; Fischer, Michael A; Kesselheim, Aaron S; Gagne, Joshua J

    2018-01-01

    Abstract Objectives To compare rates of switchbacks to branded drug products for patients switched from branded to authorized generic drug products, which have the same active ingredients, appearance, and excipients as the branded product, with patients switched from branded to generic drug products, which have the same active ingredients as the branded product but may differ in appearance and excipients. Design Observational cohort study. Setting Private (a large commercial health plan) and public (Medicaid) insurance programs in the US. Participants Beneficiaries of a large US commercial health insurer between 2004 and 2013 (primary cohort) and Medicaid beneficiaries between 2000 and 2010 (replication cohort). Main outcome measures Patients taking branded products for one of the study drugs (alendronate tablets, amlodipine tablets, amlodipine-benazepril capsules, calcitonin salmon nasal spray, escitalopram tablets, glipizide extended release tablets, quinapril tablets, and sertraline tablets) were identified when they switched to an authorized generic or a generic drug product after the date of market entry of generic drug products. These patients were followed for switchbacks to the branded drug product in the year after their switch to an authorized generic or a generic drug product. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals after adjusting for demographics, including age, sex, and calendar year. Inverse variance meta-analysis was used to pool adjusted hazard ratios across all drug products. Results A total of 94 909 patients switched from branded to authorized generic drug products and 116 017 patients switched from branded to generic drug products and contributed to the switchback analysis. Unadjusted incidence rates of switchback varied across drug products, ranging from a low of 3.8 per 100 person years (for alendronate tablets) to a high of 17.8 per 100 person years (for amlodipine

  12. Concurrent Use of Conventional Drugs with Chinese Herbal Products in Taiwan: A Population-based Study

    Directory of Open Access Journals (Sweden)

    Ming-Chen Chen

    2013-10-01

    Full Text Available The increased use of Chinese herbal products (CHPs worldwide has raised the concern of herb–drug interactions. The aim of this study was to determine the prevalence and utilization patterns of concurrent use of conventional drugs and CHPs in Taiwan. The usage and frequency of services in the co-prescription of a CHP and a conventional drug were evaluated. Subjects were recruited from a simple random sample of 1,000,000 subjects from over 22 million beneficiaries of the National Health Insurance in 2007. The logistic regression method was employed to estimate the odds ratios (ORs for the co-prescription of a CHP and a conventional drug (CH+D and a conventional drug alone (D-alone. The prevalence of the CH+D was 14.1%. Females, regular salary earners, and elderly (65 years and above were more likely to consume a CHP and a conventional drug concurrently. Painkillers, especially acetaminophen, and anti-cough medicines were the top two conventional drugs that were most frequently co-prescribed with a CHP. Anti-cough medication is the most common conventional drug co-prescribed with CHP, after painkillers. We recommend that safety issues be investigated in future research and integrating both healthcare technologies may be beneficial for the overall health and quality of life of patients.

  13. Worldwide withdrawal of medicinal products because of adverse drug reactions: a systematic review and analysis.

    Science.gov (United States)

    Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

    2016-07-01

    We have systematically identified medicinal products withdrawn worldwide because of adverse drug reactions, assessed the level of evidence used for making the withdrawal decisions, and explored the patterns of withdrawals over time. We searched PubMed, the WHO database of withdrawn products, and selected texts. We included products that were withdrawn after launch from 1950 onwards, excluding non-human and over-the-counter medicines. We assessed the levels of evidence on which withdrawals were based using the Oxford Center for Evidence Based Medicine Levels of Evidence. Of 353 medicinal products withdrawn from any country, only 40 were withdrawn worldwide. Anecdotal reports were cited as evidence for withdrawal in 30 (75%) and deaths occurred in 27 (68%). Hepatic, cardiac, and nervous system toxicity accounted for over 60% of withdrawals. In 28 cases, the first withdrawal was initiated by the manufacturer. The median interval between the first report of an adverse drug reaction that led to withdrawal and the first withdrawal was 1 year (range 0-43 years). Worldwide withdrawals occurred within 1 year after the first withdrawal in any country. In conclusion, the time it takes for drugs to be withdrawn worldwide after reports of adverse drug reactions has shortened over time. However, there are inconsistencies in current withdrawal procedures when adverse drug reactions are suspected. A uniform method for establishing worldwide withdrawal of approved medicinal products when adverse drug reactions are suspected should be developed, to facilitate global withdrawals. Rapid synthesis of the evidence on harms should be a priority when serious adverse reactions are suspected.

  14. 21 CFR 201.26 - Exceptions or alternatives to labeling requirements for human drug products held by the Strategic...

    Science.gov (United States)

    2010-04-01

    ... requirements for human drug products held by the Strategic National Stockpile. 201.26 Section 201.26 Food and... drug products held by the Strategic National Stockpile. (a) The appropriate FDA Center Director may... safety, effectiveness, or availability of such product that is or will be included in the Strategic...

  15. The effects of four different drugs administered through catheters on slime production in coagulase negative Staphylococci

    Directory of Open Access Journals (Sweden)

    J. Sedef Göçmen

    2012-12-01

    Full Text Available Objectives: Higher rate of slime production has been found in pathogen bacteria strains. Accordingly, the factors thatcontribute to higher slime production rate increase the infection risk, while the factors that reduce the slime productionrate will reduce the infection risk. The effect of some drugs that are administered through catheters in intensive careunits on slime production with coagulase negative Staphylococci was investigated.Materials and methods: In this study, the effect of four different preparations containing Glyceryl trinitrate (Perlinganit®, Dexmedetomidine (Precedex®, Esmolol (Brevibloc®, and Propofol (Propofol® on slime production of 24Staphylococcus epidermidis strains isolated from blood cultures of patients, and reference strain were investigated. Slimeproduction was determined using ‘the quantitative microdilution plaque test’ described by Christensen.Results: Under controlled medium, eight strains formed slimes, and in the media containing esmolol, glyceryl trinitrate,dexmedetomidine, and propofol slimes were positive for five, 21, 15, and 18 strains, respectively. The rate of slime productionin glyceryl trinitrate, dexmedetomidine, and propofol containing media were higher than that of the controls.Conclusions: In the light of the results of this study, it is concluded that the drugs and/or additives increase the rate ofslime production. The effects of the preparations administered through catheters on slime production should be investigated,and these effects should be kept in mind during their use. J Microbiol Infect Dis 2012; 2(4: 150-154Key words: Slime Production, Coagulase Negative Staphyloccoci, Parenteral drugs

  16. Juvenile Animal Testing: Assessing Need and Use in the Drug Product Label.

    Science.gov (United States)

    Baldrick, Paul

    2018-01-01

    Juvenile animal testing has become an established part of drug development to support safe clinical use in the human pediatric population and for eventual drug product label use. A review of European Paediatric Investigation Plan decisions showed that from 2007 to mid-2017, 229 drugs had juvenile animal work requested, almost exclusively incorporating general toxicology study designs, in rat (57.5%), dog (8%), mouse (4.5%), monkey (4%), pig (2%), sheep (1%), rabbit (1%), hamster (0.5%), and species not specified (21.5%). A range of therapeutic areas were found, but the most common areas were infectious diseases (15%), endocrinology (13.5%), oncology (13%), neurology (11%), and cardiovascular diseases (10%). Examination of major clinical indications within these therapeutic areas showed some level of consistency in the species of choice for testing and the pediatric age that required support. Examination of juvenile animal study findings presented in product labels raises questions around how useful the data are to allow prescribing the drug to a child. It is hopeful that the new ICH S11 guideline "Nonclinical Safety Testing in Support of Development of Pediatric Medicines" currently in preparation will aid drug developers in clarifying the need for juvenile animal studies as well as in promoting a move away from toxicology studies with a conventional design. This would permit more focused testing to examine identified areas of toxicity or safety concerns and clarify the presentation/interpretation of juvenile animal study findings for proper risk assessment by a drug prescriber.

  17. Strategies of bringing drug product marketing applications to meet current regulatory standards.

    Science.gov (United States)

    Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

    2015-08-01

    In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.

  18. Efeito da desodorização nas características sensoriais de extratos hidrossolúveis de soja obtidos por diferentes processos tecnológicos Effects of deodorization on sensory characteristics of hydro soluble soybean extracts obtained from different technological processes

    Directory of Open Access Journals (Sweden)

    Roberto Machado de Moraes

    2006-03-01

    Full Text Available Os produtos derivados de soja apresentam múltiplas vantagens tecnológicas e nutricionais. Entretanto, eles são pouco aceitos pela população brasileira devido às características sensoriais indesejáveis, principalmente de odor e sabor. Uma alternativa para a remoção de compostos voláteis que conferem essas características é a desodorização. Extratos hidrossolúveis de soja, comumente conhecidos como leite de soja, foram obtidos por três processos diferentes e, posteriormente, desodorizados por vapor de água superaquecido à pressão atmosférica. Os produtos nas formas bruta e desodorizada foram avaliados sensorialmente por análise descritiva quantitativa. Os resultados mostraram eficiência da desodorização pela redução do odor de feijão cru e sabor residual, com aumento do sabor característico, nos processos de obtenção do leite por vaca mecânica e por maceração.The products obtained from the soybean have shown multiple technological and nutritious advantages but, in spite of that, they haven't been easily accepted by Brazilian consumers mainly because of their unpleasant sensory characteristics of odor and flavor. Deodorization can be a good and effective method in the attempt to remove the volatile compounds that produce these characteristics. Hydro soluble soybean extracts, commonly known as soybean milk, have been obtained from three different processes and, later on, submitted to deodorization process from steaming, at atmospheric pressure. The products, both in the natural and deodorized states, have been evaluated by Quantitative Descriptive Analysis. The results have shown that the deodorization process has been effective, reducing both the raw soybean odor and the aftertaste as well, improving the typical flavor in the processes of getting the milk from "mechanical cow" or maceration.

  19. Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity.

    Science.gov (United States)

    Rayan, Anwar; Raiyn, Jamal; Falah, Mizied

    2017-01-01

    Cancer is considered one of the primary diseases that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. However, the traditional process of drug discovery and development is lengthy and expensive, so the application of in silico techniques and optimization algorithms in drug discovery projects can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index natural products for their anticancer bioactivity. Using the iterative stochastic elimination optimization technique, we obtained a highly discriminative and robust model, with an area under the curve of 0.95. Twelve natural products that scored highly as potential anticancer drug candidates are disclosed. Searching the scientific literature revealed that few of those molecules (Neoechinulin, Colchicine, and Piperolactam) have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab.

  20. Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity.

    Directory of Open Access Journals (Sweden)

    Anwar Rayan

    Full Text Available Cancer is considered one of the primary diseases that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. However, the traditional process of drug discovery and development is lengthy and expensive, so the application of in silico techniques and optimization algorithms in drug discovery projects can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index natural products for their anticancer bioactivity. Using the iterative stochastic elimination optimization technique, we obtained a highly discriminative and robust model, with an area under the curve of 0.95. Twelve natural products that scored highly as potential anticancer drug candidates are disclosed. Searching the scientific literature revealed that few of those molecules (Neoechinulin, Colchicine, and Piperolactam have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab.

  1. Vaccination of chickens against coccidiosis ameliorates drug resistance in commercial poultry production

    Directory of Open Access Journals (Sweden)

    H. David Chapman

    2014-12-01

    Full Text Available Drug resistance is a problem wherever livestock are raised under intensive conditions and drugs are used to combat parasitic infections. This is particularly true for the anticoccidial agents used for the prevention of coccidiosis caused by protozoa of the apicomplexan genus Eimeria in poultry. Resistance has been documented for all the dozen or so drugs approved for use in chickens and varying levels of resistance is present for those currently employed. A possible solution may be the introduction of drug-sensitive parasites into the houses where poultry are raised so that they may replace such drug-resistant organisms. This can be achieved by utilizing live vaccines that contain strains of Eimeria that were isolated before most anticoccidial compounds were introduced. Such strains are inherently drug-sensitive. Practical proposals to achieve this objective involve the alternation of vaccination with medication (known as rotation programs in successive flocks reared in the same poultry house. A proposal for a yearly broiler production cycle involving chemotherapy and vaccination is presented. There are few, if any, examples in veterinary parasitology where it has proved possible to restore sensitivity to drugs used to control a widespread parasite. Further research is necessary to ascertain whether this can result in sustainable and long-term control of Eimeria infections in poultry.

  2. Vaccination of chickens against coccidiosis ameliorates drug resistance in commercial poultry production

    Science.gov (United States)

    Chapman, H. David; Jeffers, Thomas K.

    2014-01-01

    Drug resistance is a problem wherever livestock are raised under intensive conditions and drugs are used to combat parasitic infections. This is particularly true for the anticoccidial agents used for the prevention of coccidiosis caused by protozoa of the apicomplexan genus Eimeria in poultry. Resistance has been documented for all the dozen or so drugs approved for use in chickens and varying levels of resistance is present for those currently employed. A possible solution may be the introduction of drug-sensitive parasites into the houses where poultry are raised so that they may replace such drug-resistant organisms. This can be achieved by utilizing live vaccines that contain strains of Eimeria that were isolated before most anticoccidial compounds were introduced. Such strains are inherently drug-sensitive. Practical proposals to achieve this objective involve the alternation of vaccination with medication (known as rotation programs) in successive flocks reared in the same poultry house. A proposal for a yearly broiler production cycle involving chemotherapy and vaccination is presented. There are few, if any, examples in veterinary parasitology where it has proved possible to restore sensitivity to drugs used to control a widespread parasite. Further research is necessary to ascertain whether this can result in sustainable and long-term control of Eimeria infections in poultry. PMID:25516830

  3. Permitting product liability litigation for FDA-approved drugs and devices promotes patient safety.

    Science.gov (United States)

    Kesselheim, A S

    2010-06-01

    In 2008 and 2009, the Supreme Court reviewed the question of whether patients injured by dangerous prescription drugs or medical devices can bring tort lawsuits against pharmaceutical and device manufacturers. The Court ruled that claims against device manufacturers were preempted while claims against pharmaceutical manufacturers were not. The threat of product liability lawsuits promotes patient safety by encouraging manufacturers to take greater responsibility in providing clear warnings about known adverse effects of their products.

  4. 78 FR 58311 - Complex Issues in Developing Drug and Biological Products for Rare Diseases; Public Workshop...

    Science.gov (United States)

    2013-09-23

    ... public workshop must register online by December 20, 2013. Early registration is recommended because...; however, it does not alter the statutory standards for marketing approval. To gain approval, all drugs must demonstrate substantial evidence of effectiveness, safety, and product quality for the treatment...

  5. 75 FR 4973 - Registration Requirements for Importers and Manufacturers of Prescription Drug Products...

    Science.gov (United States)

    2010-02-01

    ... diverted to the clandestine manufacture of a controlled substance. Most of the ephedrine, pseudoephedrine... for-profit. Other: Not-for-profit, government agencies. Abstract: The Domestic Chemical Diversion... may be diverted in the United States for the production of illicit drugs must register with DEA...

  6. 78 FR 72897 - Draft Guidance for Industry on Interim Product Reporting for Human Drug Compounding Outsourcing...

    Science.gov (United States)

    2013-12-04

    ... reporting of product information by registered outsourcing facilities under section 503B of the FD&C Act... collection techniques, when appropriate, and other forms of information technology. Under the draft guidance... report should include the following information for all drugs compounded by the outsourcing facility...

  7. 76 FR 45267 - Determination That INVERSINE (Mecamylamine Hydrochloride) Tablet and Six Other Drug Products Were...

    Science.gov (United States)

    2011-07-28

    ... products that have been discontinued from marketing for reasons other than safety or effectiveness... From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION... listed in this document were not withdrawn from sale for reasons of safety or effectiveness. This...

  8. 76 FR 11488 - Determination That MEGACE (Megestrol Acetate) Tablets and Nine Other Drug Products Were Not...

    Science.gov (United States)

    2011-03-02

    ... products that have been discontinued from marketing for reasons other than safety or effectiveness... for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION: Notice... document were not withdrawn from sale for reasons of safety or effectiveness. This determination means that...

  9. 77 FR 59403 - Determination That ENDURON (methyclothiazide) Tablets and Six Other Drug Products Were Not...

    Science.gov (United States)

    2012-09-27

    ... products that have been discontinued from marketing for reasons other than safety or effectiveness... for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION: Notice... document were not withdrawn from sale for reasons of safety or effectiveness. This determination means that...

  10. The Role of Natural Products in Drug Discovery and Development against Neglected Tropical Diseases

    Directory of Open Access Journals (Sweden)

    Peter Mubanga Cheuka

    2016-12-01

    Full Text Available Endemic in 149 tropical and subtropical countries, neglected tropical diseases (NTDs affect more than 1 billion people annually, including 875 million children in developing economies. These diseases are also responsible for over 500,000 deaths per year and are characterized by long-term disability and severe pain. The impact of the combined NTDs closely rivals that of malaria and tuberculosis. Current treatment options are associated with various limitations including widespread drug resistance, severe adverse effects, lengthy treatment duration, unfavorable toxicity profiles, and complicated drug administration procedures. Natural products have been a valuable source of drug regimens that form the cornerstone of modern pharmaceutical care. In this review, we highlight the potential that remains untapped in natural products as drug leads for NTDs. We cover natural products from plant, marine, and microbial sources including natural-product-inspired semi-synthetic derivatives which have been evaluated against the various causative agents of NTDs. Our coverage is limited to four major NTDs which include human African trypanosomiasis (sleeping sickness, leishmaniasis, schistosomiasis and lymphatic filariasis.

  11. 75 FR 74063 - Supplemental Funding Under the Food and Drug Administration's Convener of Active Medical Product...

    Science.gov (United States)

    2010-11-30

    ... the program expansion including the availability of appropriate staff and sufficient funding. 4. The...] Supplemental Funding Under the Food and Drug Administration's Convener of Active Medical Product Surveillance... expansion of its Conference Cooperative Agreement Program (U13), awarded to the Engelberg Center for Health...

  12. Limited bacterial diversity within a treatment plant receiving antibiotic containing waste from bulk drug production

    NARCIS (Netherlands)

    Marathe, Nachiket P.; Shetty, Sudarshan A.; Shouche, Yogesh S.; Larsson, D.G.J.

    2016-01-01

    Biological treatment of waste water from bulk drug production, contaminated with high levels of fluoroquinolone antibiotics, can lead to massive enrichment of antibiotic resistant bacteria, resistance genes and associated mobile elements, as previously shown. Such strong selection may be boosted

  13. Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

    Science.gov (United States)

    Kesisoglou, Filippos; Mitra, Amitava

    2015-09-01

    Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development. In this report, we show several case studies to demonstrate the potential application of absorption modeling in rational design of drug product under the QbD paradigm. The examples include application of absorption modeling—(1) prior to first-in-human studies to guide development of a formulation with minimal sensitivity to higher gastric pH and hence reduced interaction when co-administered with PPIs and/or H2RAs, (2) design of a controlled release formulation with optimal release rate to meet trough plasma concentrations and enable QD dosing, (3) understanding the impact of API particle size distribution on tablet bioavailability and guide formulation design in late-stage development, (4) assess impact of API phase change on product performance to guide specification setting, and (5) investigate the effect of dissolution rate changes on formulation bioperformance and enable appropriate specification setting. These case studies are meant to highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of the product performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

  14. Cytotoxic Drugs Departments as a precondition for high-quality product

    Directory of Open Access Journals (Sweden)

    Katarzyna Głuszek

    2014-06-01

    Full Text Available Cancer control is a tremendous challenge not only for the ill patient and physicians, but also for the whole health care system. For the first time, during the European Conference of Oncology Pharmacists, the highest standards of pharmaceutical care were proposed for cancer patients. Undoubtedly, the lifestyle and prophylaxis which would enable the detection of cancer at an early stage exert an effect on the development of the disease. Cytostatics show toxic, mutagenic, oncogenic and immunosuppressive effects; therefore, their preparation should be handled by the Central Cytotoxic Drugs Department, because the majority of the drugs prepared belong to Register A. Drugs are manufactured in accordance with GMP principles. All-Polish Standards adopted by the Polish Pharmaceutical Association delineate the direction to be developed by every hospital with respect to its own procedures and instructions. The Master of Pharmacy is responsible for the preparation of cytotoxic drugs. At one bench should work an operator and an assistant. The recommended working time should not exceed 2 h without break, and 5 h daily. The person who collects cytotoxic drugs from the Central Department should use a legible sign and a stamp including the hour and date of collection. While manufacturing cytostatics for patients in daily doses it is recommended to use concentrates in the form of solutions rather than lyophilised powders, which results in the shortening of the stage of production of the drug and reduces the possibility of forming aerosols; in the case of closed infusion systems (containers for infusion liquids which are used for the production of daily doses, the cabinet should be equipped in two tight docks for dispensing. Needleless connection of the LUER-LOCK type – a recommendation of the ISOPP – guarantees a tight connection with the drug transfer port even in the case of an increase in pressure during the manufacture of drugs. To a certain extent

  15. Development of Analytical Method and Monitoring of Veterinary Drug Residues in Korean Animal Products.

    Science.gov (United States)

    Song, Jae-Sang; Park, Su-Jeong; Choi, Jung-Yun; Kim, Jin-Sook; Kang, Myung-Hee; Choi, Bo-Kyung; Hur, Sun Jin

    2016-01-01

    This study was conducted to determine the residual amount of veterinary drugs such as meloxicam, flunixin, and tulathromycin in animal products (beef, pork, horsemeat, and milk). Veterinary drugs have been widely used in the rearing of livestock to prevent and treat diseases. A total of 152 samples were purchased from markets located in major Korean cities (Seoul, Busan, Incheon, Daegu, Daejeon, Gwangju, Ulsan and Jeju), including Jeju. Veterinary drugs were analyzed by liquid chromatography-tandem mass spectrometry according to the Korean Food Standards Code. The resulting data, which are located within 70-120% of recovery range and less than 20% of relative standard deviations, are in compliance with the criteria of CODEX. A total of five veterinary drugs were detected in 152 samples, giving a detection rate of approximately 3.3%; and no food source violated the guideline values. Our result indicated that most of the veterinary drug residues in animal products were below the maximum residue limits specified in Korea.

  16. A dataset of 200 structured product labels annotated for adverse drug reactions.

    Science.gov (United States)

    Demner-Fushman, Dina; Shooshan, Sonya E; Rodriguez, Laritza; Aronson, Alan R; Lang, Francois; Rogers, Willie; Roberts, Kirk; Tonning, Joseph

    2018-01-30

    Adverse drug reactions (ADRs), unintended and sometimes dangerous effects that a drug may have, are one of the leading causes of morbidity and mortality during medical care. To date, there is no structured machine-readable authoritative source of known ADRs. The United States Food and Drug Administration (FDA) partnered with the National Library of Medicine to create a pilot dataset containing standardised information about known adverse reactions for 200 FDA-approved drugs. The Structured Product Labels (SPLs), the documents FDA uses to exchange information about drugs and other products, were manually annotated for adverse reactions at the mention level to facilitate development and evaluation of text mining tools for extraction of ADRs from all SPLs. The ADRs were then normalised to the Unified Medical Language System (UMLS) and to the Medical Dictionary for Regulatory Activities (MedDRA). We present the curation process and the structure of the publicly available database SPL-ADR-200db containing 5,098 distinct ADRs. The database is available at https://bionlp.nlm.nih.gov/tac2017adversereactions/; the code for preparing and validating the data is available at https://github.com/lhncbc/fda-ars.

  17. 78 FR 48172 - Minimizing Risk for Children's Toy Laser Products; Draft Guidance for Industry and Food and Drug...

    Science.gov (United States)

    2013-08-07

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1092] Minimizing Risk for Children's Toy Laser Products; Draft Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food...

  18. 21 CFR 211.132 - Tamper-evident packaging requirements for over-the-counter (OTC) human drug products.

    Science.gov (United States)

    2010-04-01

    ..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...; (ii) Is prominently placed on the package; and (iii) Is so placed that it will be unaffected if the... product or, if the petition seeks an exemption for a drug class, the name of the drug class, and a list of...

  19. 21 CFR 212.90 - What actions must I take to control the distribution of PET drug products?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What actions must I take to control the... POSITRON EMISSION TOMOGRAPHY DRUGS (Eff. 12-12-2011) Distribution § 212.90 What actions must I take to control the distribution of PET drug products? (a) Written distribution procedures. You must establish...

  20. Functional evaluation of healthcare products such as cosmetics, drugs, and foods

    International Nuclear Information System (INIS)

    Hatta, Ichiro

    2008-01-01

    The present paper surveys analytical methods recently employed in the field of healthcare products such as cosmetics, drugs, and foods by using Spring-8 facility which delivers high-intensity X-ray beams from electron cyclotron accelerator. These X-ray beams can be used to analyze atoms and their chemical state in human tissues such as skin, hair, whisker, teeth, and new developed products. Thus, a variety of products related with medical supplies, health food products, health maintenance, and preventive medicine concern this research group. Here, the results on colloidal states, such as lipid-molecule aggregates and lamellar structure type, generally present in cosmetic products and food substances, are focused and reported, specifically focusing on hair cuticle and honey cell layer of the skin regarding to cosmetic and pharmaceutical products. (S. Ohno)

  1. Hybrid combinations containing natural products and antimicrobial drugs that interfere with bacterial and fungal biofilms.

    Science.gov (United States)

    Zacchino, Susana A; Butassi, Estefanía; Cordisco, Estefanía; Svetaz, Laura A

    2017-12-15

    Biofilms contribute to the pathogenesis of many chronic and difficult-to eradicate infections whose treatment is complicated due to the intrinsic resistance to conventional antibiotics. As a consequence, there is an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections. The combination therapy comprising an antimicrobial drug with a low molecular weight (MW) natural product and an antimicrobial drug (antifungal or antibacterial) appeared as a good alternative to eradicate biofilms. The aims of this review were to perform a literature search on the different natural products that have showed the ability of potentiating the antibiofilm capacity of antimicrobial drugs, to analyze which are the antimicrobial drugs most used in combination, and to have a look on the microbial species most used to prepare biofilms. Seventeen papers, nine on combinations against antifungal biofilms and eight against antibacterial biofilms were collected. Within the text, the following topics have been developed: breaf history of the discovery of biofilms; stages in the development of a biofilm; the most used methodologies to assess antibiofilm-activity; the natural products with capacity of eradicating biofilms when acting alone; the combinations of low MW natural products with antibiotics or antifungal drugs as a strategy for eradicating microbial biofilms and a list of the low MW natural products that potentiate the inhibition capacity of antifungal and antibacterial drugs against biofilms. Regarding combinations against antifungal biofilms, eight over the nine collected works were carried out with in vitro studies while only one was performed with in vivo assays by using Caenorhabditis elegans nematode. All studies use biofilms of the Candida genus. A 67% of the potentiators were monoterpenes and sesquiterpenes and six over the nine works used FCZ as the antifungal drug. The activity of AmpB and Caspo was enhanced in one and two

  2. Analyses of marketplace tacrolimus drug product quality: bioactivity, NMR and LC-MS.

    Science.gov (United States)

    Sommers, Cynthia D; Pang, Eric S; Ghasriani, Houman; Berendt, Robert T; Vilker, Vincent L; Keire, David A; Boyne, Michael T

    2013-11-01

    Tacrolimus (FK506) is a potent, narrow therapeutic index, immunosuppressive drug used to avoid organ rejection in patients that have undergone organ transplantation. Recent clinical reports suggested a significant reduction in the tacrolimus concentration/dose ratio in the plasma of liver and kidney recipients when the reference listed drug was substituted with a generic drug. In response to these concerns about switching between tacrolimus from different approved manufacturers during treatment, the FDA initiated purity, potency and quality studies of the innovator and generic tacrolimus products available in the US marketplace. A combination of analytical methods, including mass spectrometry (LC-MS), nuclear magnetic resonance (NMR) and bioactivity assay were developed and validated to assess the quality of tacrolimus. These tests measured the identity, impurities and activity of tacrolimus from active pharmaceutical ingredient (API) sources and with formulated drug product from five different approved manufactures. In addition, some testing was performed on tacrolimus capsules obtained from a non US approved Indian source. The data obtained showed no discernible difference in the impurity profiles and potency between the generic and innovator tacrolimus products. Copyright © 2013. Published by Elsevier B.V.

  3. VETSTAT - the Danish system for surveillance of the veterinary use of drugs for production animals

    DEFF Research Database (Denmark)

    Stege, H.; Bager, Flemming; Jacobsen, Erik

    2003-01-01

    The Danish Ministry of Food, Agriculture and Fisheries funds a monitoring system based on drug usage information collected at the herd level: VETSTAT. VETSTAT is constructed as a relational database and data originates from three sources: pharmacies, veterinarians and feed mills. All administration...... of drugs for use in animal production is reported on a monthly basis. Pharmacies provided 95% of the total weight antimicrobial compounds used in Denmark in 2001. More than 80% of the antimicrobial compounds reported by pharmacies were sold on prescription to end-users (owners) and included information...

  4. Analysis of veterinary drug residue monitoring results for commercial livestock products in Taiwan between 2011 and 2015

    Directory of Open Access Journals (Sweden)

    Hsin-Chun Lee

    2018-04-01

    Full Text Available Antibiotics have been widely used in the treatment of livestock diseases. However, the emergence of issues related to drug resistance prompted governments to enact a series of laws regulating the use of antibiotics in livestock. Following control of the problem of drug resistant bacteria, public attention has shifted to the recurring incidence of human health and safety issues caused by residual veterinary drugs in livestock products. To guarantee the safety and hygiene of meat, milk, and eggs from food-producing animals, governments and relevant agencies established laws and regulations for the use of veterinary drugs. It is, therefore, necessary to monitor the content of residual drugs in livestock products at regular intervals to assess whether the regulations have resulted in the effective management of food product safety, and to prevent and manage sudden problems related to this issue. A 2011–2015 livestock product post-marketing monitoring program launched by the Taiwan Food and Drug Administration (TFDA inspected 1487 livestock products. Over the past 5 years, there were 34 samples identified that did not conform to the regulations; these samples included residue drugs such as β-agonists, chloramphenicols, β-lactam antibiotics, sulfa drugs, enrofloxacin, and lincomycin. Inspections of commercial livestock products with the consistent cooperation of agricultural authorities did not detect the drugs that were banned by the government, whereas the detection of other drugs decreased annually with an increase in the post-market monitoring sample size. In the future, the TFDA will continue to monitor the status of residual veterinary drugs in commercial livestock products, adjust the sampling of food products annually according to monitoring results, and closely cooperate with agricultural authorities on source management. Keywords: Agricultural authorities, Livestock products, Post-market monitoring, Veterinary drug residues

  5. Evaluación de la toxicidad del desodorante RLV en ojos Evaluation of RLV deodorant toxicity in eyes

    Directory of Open Access Journals (Sweden)

    Esvieta Tenorio Borroto

    2001-12-01

    Full Text Available Se realizó la evaluación del posible efecto irritante de un formulado (RLV que se empleará como desodorante y que contiene como principio activo la hexamina, la cual es empleada como antiséptico urinario. Este formulado se aplicó por vía oftálmica en 6 conejos de la raza Nueva Zelandia, durante 7 días. Las valoraciones se basan en las observaciones macroscópicas de los posibles efectos adversos que se presentan en las estructuras oculares. Para esta evaluación nos basamos en el método propuesto por Draize, así como las guías de la OECD, de acuerdo con los resultados obtenidos la forma farmacéutica elaborada a una concentración del 3 % para el desodorante, no ocasiona irritación en las estructuras oculares.An evaluation of the possible irritant effect of a formulation (RLV that will be used as a deodorant and whose active principle is hexamine, which is utilized as a urinary antiseptic, was made. This formulation was applied by ophthalmic route to 6 New Zealand breed rabbits during 7 days. The assessments take into consideration the macroscopic observations of the possible adverse effects that occur in the ocular structures. This evaluation is based on the method proposed by Draize, as well as on the guidelines of the OECD. According to the results obtained, the pharmaceutical form prepared at a concentration of 3 % for the deodorant does not cause irritation of the ocular structures.

  6. 75 FR 75482 - Draft Guidance for Industry on Residual Solvents in Animal Drug Products; Questions and Answers...

    Science.gov (United States)

    2010-12-03

    ...] Draft Guidance for Industry on Residual Solvents in Animal Drug Products; Questions and Answers... Solvents in Animal Drug Products; Questions and Answers.'' The draft questions and answers (Q&A) guidance addresses the United States Pharmacopeia (USP) General Chapter Residual Solvents that applies to both human...

  7. Review on research of suppression male fertility and male contraceptive drug development by natural products.

    Science.gov (United States)

    Bajaj, Vijay Kumar; Gupta, Radhey S

    2013-08-01

    Male contraceptive development in the present scenario is most viable aspect of research due to uncontrolled population growth in the world. In this respect investigators are busy to find out a safe male contraceptive drug. Researchers have started their finding for a suitable drug from natural sources because these are safe and easily acceptable for common man, most of natural sources are plants and their products. In this review 137 plants and their effects on reproduction and reproductive physiology are summarized. Some of them have intense effect on male reproductive system and do not produce any side effects. Reproductive toxicological studies are also important aspects of these kinds of researches, so it is important that drugs are safe and widely acceptable. An ideal male contraceptive can influence semen, testes, hormone level, accessory reproductive organs and general physiology of animals and produced some alterations. Many plants in this review are showing antifertility as well as antispermatogenic effects, so these may be used for further study for contraceptives development but it is important to find out the mechanism of reaction and further laboratory and clinical research on some plants are needed for final male contraceptive drug development. In conclusion this review will help for finding suitable plant products for male contraceptive clinical and laboratory studies.

  8. Essential Drugs Production in Brazil, Russia, India, China and South Africa (BRICS: Opportunities and Challenges

    Directory of Open Access Journals (Sweden)

    Zoheir Ezziane

    2014-12-01

    Full Text Available The objective of this work is to elucidate various essential drugs in the Brazil, Russia, India, China and South Africa (BRICS countries. It discusses the opportunities and challenges of the existing biotech infrastructure and the production of drugs and vaccines in member states of the BRICS. This research is based on a systematic literature review between the years 2000 and 2014 of documents retrieved from the databases Embase, PubMed/Medline, Global Health, and Google Scholar, and the websites of relevant international organizations, research institutions and philanthropic organizations. Findings vary from one member state to another. These include useful comparison between the BRICS countries in terms of pharmaceuticals expenditure versus total health expenditure, local manufacturing of drugs/vaccines using technology and know-how transferred from developed countries, and biotech entrepreneurial collaborations under the umbrella of the BRICS region. This study concludes by providing recommendations to support more of inter collaborations among the BRICS countries as well as between BRICS and many developing countries to shrink drug production costs. In addition, this collaboration would also culminate in reaching out to poor countries that are not able to provide their communities and patients with cost-effective essential medicines.

  9. Comparison of Clobetasol Propionate Generics Using Simplified in Vitro Bioequivalence Method for Topical Drug Products.

    Science.gov (United States)

    Soares, Kelen Carine Costa; de Souza, Weidson Carlos; de Souza Texeira, Leonardo; da Cunha-Filho, Marcilio Sergio Soares; Gelfuso, Guilherme Martins; Gratieri, Tais

    2017-11-20

    The aim of this paper is to propose a simple in vitro skin penetration experiment in which the drug is extracted from the whole skin piece as a test valid for formulation screening and optimization during development process, equivalence assessment during quality control or post-approval after changes to the product. Twelve clobetasol propionate (CP) formulations (six creams and six ointments) from the local market were used as a model to challenge the proposed methodology in comparison to in vitro skin penetration following tape-stripping for drug extraction. To support the results, physicochemical tests for pH, viscosity, density and assay, as well as in vitro release were performed. Both protocols, extracting the drug from the skin using the tape-stripping technique or extracting from the full skin were capable of differentiating CP formulations. Only one formulation did not present statistical difference from the reference drug product in penetration tests and only other two oitments presented equivalent release to the reference. The proposed protocol is straightforward and reproducible. Results suggest the bioinequavalence of tested CP formulations reinforcing the necessity of such evaluations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Essential drugs production in Brazil, Russia, India, China and South Africa (BRICS): opportunities and challenges.

    Science.gov (United States)

    Ezziane, Zoheir

    2014-12-01

    The objective of this work is to elucidate various essential drugs in the Brazil, Russia, India, China and South Africa (BRICS) countries. It discusses the opportunities and challenges of the existing biotech infrastructure and the production of drugs and vaccines in member states of the BRICS. This research is based on a systematic literature review between the years 2000 and 2014 of documents retrieved from the databases Embase, PubMed/Medline, Global Health, and Google Scholar, and the websites of relevant international organizations, research institutions and philanthropic organizations. Findings vary from one member state to another. These include useful comparison between the BRICS countries in terms of pharmaceuticals expenditure versus total health expenditure, local manufacturing of drugs/vaccines using technology and know-how transferred from developed countries, and biotech entrepreneurial collaborations under the umbrella of the BRICS region. This study concludes by providing recommendations to support more of inter collaborations among the BRICS countries as well as between BRICS and many developing countries to shrink drug production costs. In addition, this collaboration would also culminate in reaching out to poor countries that are not able to provide their communities and patients with cost-effective essential medicines.

  11. 77 FR 22327 - Draft Guidance for Industry on New Animal Drugs and New Animal Drug Combination Products...

    Science.gov (United States)

    2012-04-13

    ... resistance in human and animal bacterial pathogens when medically important antimicrobial drugs are used in... Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals'' and to set timelines... Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals'' (GFI 209) and (2) the...

  12. Analysis of veterinary drug residue monitoring results for commercial livestock products in Taiwan between 2011 and 2015.

    Science.gov (United States)

    Lee, Hsin-Chun; Chen, Chi-Min; Wei, Jen-Ting; Chiu, Hsiu-Yi

    2018-04-01

    Antibiotics have been widely used in the treatment of livestock diseases. However, the emergence of issues related to drug resistance prompted governments to enact a series of laws regulating the use of antibiotics in livestock. Following control of the problem of drug resistant bacteria, public attention has shifted to the recurring incidence of human health and safety issues caused by residual veterinary drugs in livestock products. To guarantee the safety and hygiene of meat, milk, and eggs from food-producing animals, governments and relevant agencies established laws and regulations for the use of veterinary drugs. It is, therefore, necessary to monitor the content of residual drugs in livestock products at regular intervals to assess whether the regulations have resulted in the effective management of food product safety, and to prevent and manage sudden problems related to this issue. A 2011-2015 livestock product post-marketing monitoring program launched by the Taiwan Food and Drug Administration (TFDA) inspected 1487 livestock products. Over the past 5 years, there were 34 samples identified that did not conform to the regulations; these samples included residue drugs such as β-agonists, chloramphenicols, β-lactam antibiotics, sulfa drugs, enrofloxacin, and lincomycin. Inspections of commercial livestock products with the consistent cooperation of agricultural authorities did not detect the drugs that were banned by the government, whereas the detection of other drugs decreased annually with an increase in the post-market monitoring sample size. In the future, the TFDA will continue to monitor the status of residual veterinary drugs in commercial livestock products, adjust the sampling of food products annually according to monitoring results, and closely cooperate with agricultural authorities on source management. Copyright © 2017. Published by Elsevier B.V.

  13. Accelerated approval of oncology products: the food and drug administration experience.

    Science.gov (United States)

    Johnson, John R; Ning, Yang-Min; Farrell, Ann; Justice, Robert; Keegan, Patricia; Pazdur, Richard

    2011-04-20

    We reviewed the regulatory history of the accelerated approval process and the US Food and Drug Administration (FDA) experience with accelerated approval of oncology products from its initiation in December 11, 1992, to July 1, 2010. The accelerated approval regulations allowed accelerated approval of products to treat serious or life-threatening diseases based on surrogate endpoints that are reasonably likely to predict clinical benefit. Failure to complete postapproval trials to confirm clinical benefit with due diligence could result in removal of the accelerated approval indication from the market. From December 11, 1992, to July 1, 2010, the FDA granted accelerated approval to 35 oncology products for 47 new indications. Clinical benefit was confirmed in postapproval trials for 26 of the 47 new indications, resulting in conversion to regular approval. The median time between accelerated approval and regular approval of oncology products was 3.9 years (range = 0.8-12.6 years) and the mean time was 4.7 years, representing a substantial time savings in terms of earlier availability of drugs to cancer patients. Three new indications did not show clinical benefit when confirmatory postapproval trials were completed and were subsequently removed from the market or had restricted distribution plans implemented. Confirmatory trials were not completed for 14 new indications. The five longest intervals from receipt of accelerated approval to July 1, 2010, without completion of trials to confirm clinical benefit were 10.5, 6.4, 5.5, 5.5, and 4.7 years. The five longest intervals between accelerated approval and successful conversion to regular approval were 12.6, 9.7, 8.1, 7.5, and 7.4 years. Trials to confirm clinical benefit should be part of the drug development plan and should be in progress at the time of an application seeking accelerated approval to prevent an ineffective drug from remaining on the market for an unacceptable time.

  14. Thermodynamics of Highly Supersaturated Aqueous Solutions of Poorly Water-Soluble Drugs-Impact of a Second Drug on the Solution Phase Behavior and Implications for Combination Products.

    Science.gov (United States)

    Trasi, Niraj S; Taylor, Lynne S

    2015-08-01

    There is increasing interest in formulating combination products that contain two or more drugs. Furthermore, it is also common for different drug products to be taken simultaneously. This raises the possibility of interactions between different drugs that may impact formulation performance. For poorly water-soluble compounds, the supersaturation behavior may be a critical factor in determining the extent of oral absorption. The goal of the current study was to evaluate the maximum achievable supersaturation for several poorly water-soluble compounds alone, and in combination. Model compounds included ritonavir, lopinavir, paclitaxel, felodipine, and diclofenac. The "amorphous solubility" for the pure drugs was determined using different techniques and the change in this solubility was then measured in the presence of differing amounts of a second drug. The results showed that "amorphous solubility" of each component in aqueous solution is substantially decreased by the second component, as long as the two drugs are miscible in the amorphous state. A simple thermodynamic model could be used to predict the changes in solubility as a function of composition. This information is of great value when developing co-amorphous or other supersaturating formulations and should contribute to a broader understanding of drug-drug physicochemical interactions in in vitro assays as well as in the gastrointestinal tract. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  15. Regulatory Notes on Impact of Excipients on Drug Products and the Maillard Reaction.

    Science.gov (United States)

    Chowdhury, Dipak K; Sarker, Haripada; Schwartz, Paul

    2018-02-01

    In general, it is an important criterion that excipients remain inert throughout the shelf life of the formulated pharmaceutical product. However, depending on the functionality in chemical structure of active drug and excipients, they may undergo interaction. The well-known Maillard reaction occurs between a primary amine with lactose at high temperature to produce brown pigments. The reactivity of Maillard reaction may vary depending on the concentration as well as other conditions. Commercially, there are products where the active pharmaceutical ingredient is a primary amine and contains less than 75% lactose along with inactive excipients. This product does not show Maillard reaction during its shelf life of around 2 years at ambient conditions. However, when the same type of product contains more than 95 % lactose as an excipient, then there is a possibility of interactions though it is not visible in the initial year. Therefore, this regulatory note discusses involvement of different factors of a known drug-excipient interactions with case studies and provides an overview on how the concentration of lactose in the pharmaceutical product is important in addition to temperature and moisture in Maillard reaction.

  16. Quality by design case study: an integrated multivariate approach to drug product and process development.

    Science.gov (United States)

    Huang, Jun; Kaul, Goldi; Cai, Chunsheng; Chatlapalli, Ramarao; Hernandez-Abad, Pedro; Ghosh, Krishnendu; Nagi, Arwinder

    2009-12-01

    To facilitate an in-depth process understanding, and offer opportunities for developing control strategies to ensure product quality, a combination of experimental design, optimization and multivariate techniques was integrated into the process development of a drug product. A process DOE was used to evaluate effects of the design factors on manufacturability and final product CQAs, and establish design space to ensure desired CQAs. Two types of analyses were performed to extract maximal information, DOE effect & response surface analysis and multivariate analysis (PCA and PLS). The DOE effect analysis was used to evaluate the interactions and effects of three design factors (water amount, wet massing time and lubrication time), on response variables (blend flow, compressibility and tablet dissolution). The design space was established by the combined use of DOE, optimization and multivariate analysis to ensure desired CQAs. Multivariate analysis of all variables from the DOE batches was conducted to study relationships between the variables and to evaluate the impact of material attributes/process parameters on manufacturability and final product CQAs. The integrated multivariate approach exemplifies application of QbD principles and tools to drug product and process development.

  17. Rapid determination of free fatty acid content in waste deodorizer distillates using single bounce-attenuated total reflectance-FTIR spectroscopy.

    Science.gov (United States)

    Naz, Saba; Sherazi, Sayed Tufail Hussain; Talpur, Farah N; Mahesar, Sarfaraz A; Kara, Huseyin

    2012-01-01

    A simple, rapid, economical, and environmentally friendly analytical method was developed for the quantitative assessment of free fatty acids (FFAs) present in deodorizer distillates and crude oils by single bounce-attenuated total reflectance-FTIR spectroscopy. Partial least squares was applied for the calibration model based on the peak region of the carbonyl group (C=O) from 1726 to 1664 cm(-1) associated with the FFAs. The proposed method totally avoided the use of organic solvents or costly standards and could be applied easily in the oil processing industry. The accuracy of the method was checked by comparison to a conventional standard American Oil Chemists' Society (AOCS) titrimetric procedure, which provided good correlation (R = 0.99980), with an SD of +/- 0.05%. Therefore, the proposed method could be used as an alternate to the AOCS titrimetric method for the quantitative determination of FFAs especially in deodorizer distillates.

  18. Batch-to-Batch Quality Consistency Evaluation of Botanical Drug Products Using Multivariate Statistical Analysis of the Chromatographic Fingerprint

    OpenAIRE

    Xiong, Haoshu; Yu, Lawrence X.; Qu, Haibin

    2013-01-01

    Botanical drug products have batch-to-batch quality variability due to botanical raw materials and the current manufacturing process. The rational evaluation and control of product quality consistency are essential to ensure the efficacy and safety. Chromatographic fingerprinting is an important and widely used tool to characterize the chemical composition of botanical drug products. Multivariate statistical analysis has showed its efficacy and applicability in the quality evaluation of many ...

  19. Drug Product Life-Cycle Management as Anticompetitive Behavior: The Case of Memantine.

    Science.gov (United States)

    Capati, Vincent C; Kesselheim, Aaron S

    2016-04-01

    A "product hop" involves the substitution of a new formulation of a prescription drug by a pharmaceutical manufacturer for an old version to forestall generic competition. In 2015, for example, Forest Laboratories, the brand-name drug manufacturer of memantine, an Alzheimer's disease treatment, introduced an extended-release version and tried to restrict patient access to the previous version. Product hops can lead to useful incremental innovation but can also have major public health implications by disrupting patients on stable treatment regimens and increasing costs for patients and payers. This commentary reviews alleged anticompetitive product hopping in the case of memantine, which involved proposed conduct that would have left Alzheimer's disease patients with no effective choice but to transition to memantine XR. Policy solutions that can limit anticompetitive product hops include raising the bar for obtaining patents on new drug product formulations and changing automatic generic substitution laws. No outside funding supported this research. To support his work at PORTAL in the summer of 2015, Capati was the recipient of the University of New Hampshire School of Law Rudman Center Public Service Fellowship. Kesselheim's research was supported by Greenwall Faculty Scholars program, the Laura and John Arnold Foundation, and the Harvard Program in Therapeutic Science. In 2013, Kesselheim served as an expert on behalf of a class of individual plaintiffs against Warner Chilcott regarding potential antitrust violations Kesselheim was responsible for concept and design of this commentary. Capati took the lead in data collection and analysis, along with Kesselheim. Capati wrote the manuscript, which was revised by primarily by Kesselheim, along with Capati.

  20. [HERA-QUEST: HTA evaluation of generic pharmaceutical products to improve quality, economic efficiency, patient safety and transparency in drug product changes in hospitals].

    Science.gov (United States)

    Gyalrong-Steur, Miriam; Kellermann, Anita; Bernard, Rudolf; Berndt, Georg; Bindemann, Meike; Nusser-Rothermundt, Elfriede; Amann, Steffen; Brakebusch, Myga; Brüggmann, Jörg; Tydecks, Eva; Müller, Markus; Dörje, Frank; Kochs, Eberhard; Riedel, Rainer

    2017-04-01

    In view of the rising cost pressure and an increasing number of drug shortages, switches between generic drug preparations have become a daily routine in hospitals. To ensure consistently high treatment quality and best possible patient safety, the equivalence of the new and the previous drug preparation must be ensured before any change in the purchase of pharmaceutical products takes place. So far, no easily usable, transparent and standardized instrument for this kind of comparison between generic drug products has been available. A group of pharmaceutical experts has developed the drug HTA (health technology assessment) model "HERA" (HTA Evaluation of geneRic phArmaceutical products) through a multi-step process. The instrument is designed to perform both a qualitative and economic comparison of equivalent drug preparations ("aut idem" substitution) before switching products. The economic evaluation does not only consider unit prices and consumption quantity, but also the processing costs associated with a product change process. The qualitative comparison is based on the evaluation of 34 quality criteria belonging to six evaluation fields (e.g., approval status, practical handling, packaging design). The objective evaluation of the quality criteria is complemented by an assessment of special features of the individual hospital for complex drug switches, including the feedback of the physicians utilizing the drug preparation. Thus potentially problematic switches of pharmaceutical products can be avoided at the best possible rate, contributing to the improvement of patient safety. The novel drug HTA model HERA is a tool used in clinical practice that can add to an increase in quality, therapeutic safety and transparency of drug use while simultaneously contributing to the economic optimization of drug procurement in hospitals. Combining these two is essential for hospitals facing the tension between rising cost pressure and at the same time increasing demands

  1. Natural products against cancer: A comprehensive bibliometric study of the research projects, publications, patents and drugs

    Directory of Open Access Journals (Sweden)

    Jian Du

    2014-01-01

    Full Text Available Objectives: To analyze multi-source data including awards, publications, patents and drugs, and try to draw the whole landscape of the research and development community in the area of natural products (NPs against cancer. Materials and Methods: Awards, publications, patents and drugs data from National Institute of Health/Natural Science Foundation of China (NIH/NSFC, PubMed, Derwent Innovation Index and Cortellis were collected. Bibliometric methodologies and technology are used to investigate publications/patents/drugs, their contents and relationships. Results: NIH and NSFC respectively demonstrated a stable and sustained expenditure growth in this area. The number of publications is continuously increasing. Yet the annual patent applications worldwide and FDA drug approvals were little changed or not obviously fluctuated in 2003-2013. USA and several Asia-pacific countries/territories are important contributing powers. We described the evolution of major research topics by those MeSH Major Topics indexed in PubMed with the largest growth range in three intervals, and analyzed hot research topics in the recent 10 years which include NPs or NPs derivatives, cell line/animal model, laboratory technologies and activation mechanisms. Conclusions: China published the most publications and received the most patent applications, but drug discovery performance is no better than USA and Japan. Research on anti-neoplastic structures and compounds originated from Chinese traditional medicine (TCM, medicinal plants, herbal medicine and marine NPs are major research topics in the recent 10 years. There still exits translational gap between basic research and drug discovery. Translational research should be undertaken to strengthen the applicability of NPs.

  2. Provisional in-silico biopharmaceutics classification (BCS) to guide oral drug product development.

    Science.gov (United States)

    Wolk, Omri; Agbaria, Riad; Dahan, Arik

    2014-01-01

    The main objective of this work was to investigate in-silico predictions of physicochemical properties, in order to guide oral drug development by provisional biopharmaceutics classification system (BCS). Four in-silico methods were used to estimate LogP: group contribution (CLogP) using two different software programs, atom contribution (ALogP), and element contribution (KLogP). The correlations (r(2)) of CLogP, ALogP and KLogP versus measured LogP data were 0.97, 0.82, and 0.71, respectively. The classification of drugs with reported intestinal permeability in humans was correct for 64.3%-72.4% of the 29 drugs on the dataset, and for 81.82%-90.91% of the 22 drugs that are passively absorbed using the different in-silico algorithms. Similar permeability classification was obtained with the various in-silico methods. The in-silico calculations, along with experimental melting points, were then incorporated into a thermodynamic equation for solubility estimations that largely matched the reference solubility values. It was revealed that the effect of melting point on the solubility is minor compared to the partition coefficient, and an average melting point (162.7 °C) could replace the experimental values, with similar results. The in-silico methods classified 20.76% (± 3.07%) as Class 1, 41.51% (± 3.32%) as Class 2, 30.49% (± 4.47%) as Class 3, and 6.27% (± 4.39%) as Class 4. In conclusion, in-silico methods can be used for BCS classification of drugs in early development, from merely their molecular formula and without foreknowledge of their chemical structure, which will allow for the improved selection, engineering, and developability of candidates. These in-silico methods could enhance success rates, reduce costs, and accelerate oral drug products development.

  3. Quality Characteristics of Iranian Extra Virgin Flaxseed Oil and the Effect of the Refining Stages before Deodorization on its Physicochemical Properties

    OpenAIRE

    Manochehr Bahmaei; Yousef Ramezan; Parvin Eshratabadi

    2017-01-01

    Flaxseed oil is known as a functional oil because of the high content of α-linolenic acid; therefore, the aim of this research was to investigate some physicochemical properties of Iranian extra virgin flaxseed oil (EVFO) and the impact of the refining stages before deodorization on these properties. Fatty acid composition, peroxide and anisidine values, free fatty acids, Crystallization point, chlorophyll content, β-carotene content, and color were analyzed. The Iranian flaxseed oils had abo...

  4. Bringing smart pills to market: FDA regulation of ingestible drug/device combination products.

    Science.gov (United States)

    Avery, Matthew; Liu, Dan

    2011-01-01

    Imagine a pill that, after you swallow it, can track its position in your body. Or imagine a pill that can transmit a message to a doctor to tell him that you have taken your bitter medicine. Pills like this already exist. These so-called smart pills are an emerging type of medical therapy. However, this nascent technology has yet to reach the market and developers of these novel therapies face significant regulatory challenges. This article predicts how the Food and Drug Administration will regulate smart pills and shows how the current regulatory regime is inadequate. The article then proposes modifying the current regulatory regime to encourage development of smart pills and other innovative combination products by: (1) regulating combination products based on their "novel mode of action" rather than their "primary mode of action," (2) creating a marketing approval pathway specifically for combination products, and (3) eliminating regulations that require sponsors to get marketing approval from multiple centers within FDA and providing regulatory guidance specifically for ingestible drug/device combination products.

  5. Patient Drug Safety Reporting: Diabetes Patients' Perceptions of Drug Safety and How to Improve Reporting of Adverse Events and Product Complaints.

    Science.gov (United States)

    Patel, Puja; Spears, David; Eriksen, Betina Østergaard; Lollike, Karsten; Sacco, Michael

    2018-03-01

    Global health care manufacturer Novo Nordisk commissioned research regarding awareness of drug safety department activities and potential to increase patient feedback. Objectives were to examine patients' knowledge of pharmaceutical manufacturers' responsibilities and efforts regarding drug safety, their perceptions and experiences related to these efforts, and how these factors influence their thoughts and behaviors. Data were collected before and after respondents read a description of a drug safety department and its practices. We conducted quantitative survey research across 608 health care consumers receiving treatment for diabetes in the United States, Germany, United Kingdom, and Italy. This research validated initial, exploratory qualitative research (across 40 comparable consumers from the same countries) which served to guide design of the larger study. Before reading a drug safety department description, 55% of respondents were unaware these departments collect safety information on products and patients. After reading the description, 34% reported the department does more than they expected to ensure drug safety, and 56% reported "more confidence" in the industry as a whole. Further, 66% reported themselves more likely to report an adverse event or product complaint, and 60% reported that they were more likely to contact a drug safety department with questions. The most preferred communication methods were websites/online forums (39%), email (27%), and telephone (25%). Learning about drug safety departments elevates consumers' confidence in manufacturers' safety efforts and establishes potential for patients to engage in increased self-monitoring and reporting. Study results reveal potentially actionable insights for the industry across patient and physician programs and communications.

  6. Activation of Antibiotic Production in Bacillus spp. by Cumulative Drug Resistance Mutations.

    Science.gov (United States)

    Tojo, Shigeo; Tanaka, Yukinori; Ochi, Kozo

    2015-12-01

    Bacillus subtilis strains produce a wide range of antibiotics, including ribosomal and nonribosomal peptide antibiotics, as well as bacilysocin and neotrehalosadiamine. Mutations in B. subtilis strain 168 that conferred resistance to drugs such as streptomycin and rifampin resulted in overproduction of the dipeptide antibiotic bacilysin. Cumulative drug resistance mutations, such as mutations in the mthA and rpsL genes, which confer low- and high-level resistance, respectively, to streptomycin, and mutations in rpoB, which confer resistance to rifampin, resulted in cells that overproduced bacilysin. Transcriptional analysis demonstrated that the enhanced transcription of biosynthesis genes was responsible for the overproduction of bacilysin. This approach was effective also in activating the cryptic genes of Bacillus amyloliquefaciens, leading to actual production of antibiotic(s). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Analysis of veterinary drug residue monitoring results for commercial livestock products in Taiwan between 2011 and 2015

    OpenAIRE

    Hsin-Chun Lee; Chi-Min Chen; Jen-Ting Wei; Hsiu-Yi Chiu

    2018-01-01

    Antibiotics have been widely used in the treatment of livestock diseases. However, the emergence of issues related to drug resistance prompted governments to enact a series of laws regulating the use of antibiotics in livestock. Following control of the problem of drug resistant bacteria, public attention has shifted to the recurring incidence of human health and safety issues caused by residual veterinary drugs in livestock products. To guarantee the safety and hygiene of meat, milk, and egg...

  8. A simple method for purification of deodorizer distillate from Indian rice (Oryza Sativa bran oil and preparation of phytosterols

    Directory of Open Access Journals (Sweden)

    Raja Rajan, R. G.

    2014-12-01

    Full Text Available Samples of rice bran oil deodorizer distillates (RBO DOD-1 and RBO DOD-2 were studied for their physicochemical characteristics. The samples were semisolid and had a dark color. The free fatty acid values were 59.2% and 86.0%, the unsaponifiable matter was 18.7% and 7.75% and the phytosterol contents were 8.71% and 4.22%, respectively for the deodorizer distillates studied. A simple method of silica gel percolation was developed to purify DOD to obtain phytosterol concentrate fractions (PCF and a brown color and bad odor fraction (BCBOF. The color values were reduced by 72.8% and 73.0% of lovibond units in the PCF for DOD-1 and DOD-2 respectively, had no bad odor and were increased in the phytosterol concentration to 12.4% and 5.9%. The PCF was further processed to prepare high purity phytosterols. An HPLC analysis of the phytosterol mixture showed it to be formed by β-sitosterol (38.2%, stigmasterol (34.9%, campesterol (9.5% and other sterols (17.4%.Se estudiaron las características físico-químicas de muestras de destilados de desodorización de aceites de salvado de arroz (RBO DOD-1 y RBO DOD-2. Las muestras eran semi-sólidas y tenían un color oscuro. Los valores de ácidos grasos libres fueron 59,2% y 86,0%, materia insaponificable 18,7% y 7,75% y contenido de fitoesteroles de 8,71% y 4,22%, respectivamente, para los destilados de desodorización estudiados. Se desarrolló un método simple de filtración mediante sílica gel para purificar DOD y obtener concentrados de fitosteroles (PCF y una fracción de color marrón y olor desagradable (BCBOF. Los valores de color se redujeron en un 72,8% y el 73,0% de unidades Lovibond en el PCF para DOD-1 y DOD-2, respectivamente, no tenían mal olor y aumentaron su concentración en fitoesteroles al 12,4% y 5,9%. El PCF se procesó adicionalmente para preparar fitosteroles de alta pureza. El análisis por HPLC mostró que la mezcla de fitosteroles estaba formada por β-sitosterol (38

  9. 75 FR 55676 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications...

    Science.gov (United States)

    2010-09-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510, 520, and...; International Nutrition, Inc., 7706 ``I'' Plaza, Omaha, NE 68127; and Feed Service Co., Inc., 303 Lundin Blvd... 520--ORAL DOSAGE FORM NEW ANIMAL DRUGS 0 3. The authority citation for 21 CFR part 520 continues to...

  10. 76 FR 17776 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications...

    Science.gov (United States)

    2011-03-31

    ...'s Sponsor (established name of drug) drug labeler code) Roche Vitamins, Inc., 45 Waterview Blvd.... Medicator TS-40 Premix (tylosin phosphate/ sulfamethazine). Pegasus Laboratories, Inc., 8809 Ely Rd., NADA... Laboratories, Inc., 100 Nancy Dr., NADA 108-487, DEC Tabs 520.622a (015579). Belle Plaine, MN 56011...

  11. Principal component analysis as a tool for library design: a case study investigating natural products, brand-name drugs, natural product-like libraries, and drug-like libraries.

    Science.gov (United States)

    Wenderski, Todd A; Stratton, Christopher F; Bauer, Renato A; Kopp, Felix; Tan, Derek S

    2015-01-01

    Principal component analysis (PCA) is a useful tool in the design and planning of chemical libraries. PCA can be used to reveal differences in structural and physicochemical parameters between various classes of compounds by displaying them in a convenient graphical format. Herein, we demonstrate the use of PCA to gain insight into structural features that differentiate natural products, synthetic drugs, natural product-like libraries, and drug-like libraries, and show how the results can be used to guide library design.

  12. Natural products as promising drug candidates for the treatment of Alzheimer's disease: molecular mechanism aspect.

    Science.gov (United States)

    Ansari, Niloufar; Khodagholi, Fariba

    2013-07-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder to date, with no curative or preventive therapy. Histopathological hallmarks of AD include deposition of β-amyloid plaques and formation of neurofibrillary tangles. Extent studies on pathology of the disease have made important discoveries regarding mechanism of disease and potential therapeutic targets. Many cellular changes including oxidative stress, disruption of Ca2+ homeostasis, inflammation, metabolic disturbances, and accumulation of unfolded/misfolded proteins can lead to programmed cell death in AD. Despite intensive research, only five approved drugs are available for the management of AD. Hence, there is a need to look at alternative therapies. Use of natural products and culinary herbs in medicine has gained popularity in recent years. Several natural substances with neuroprotective effects have been widely studied. Most of these compounds have remarkable antioxidant properties and act mainly by scavenging free radical species. Some of them increase cell survival and improve cognition by directly affecting amyloidogenesis and programmed cell death pathways. Further studies on these natural products and their mechanism of action, parallel with the use of novel pharmaceutical drug design and delivery techniques, enable us to offer an addition to conventional medicine. This review discussed some natural products with potential neuroprotective properties against Aβ with respect to their mechanism of action.

  13. Virtual target screening to rapidly identify potential protein targets of natural products in drug discovery

    Directory of Open Access Journals (Sweden)

    Yuri Pevzner

    2014-05-01

    Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.

  14. Virtual target screening to rapidly identify potential protein targets of natural products in drug discovery

    Directory of Open Access Journals (Sweden)

    Yuri Pevzner

    2015-08-01

    Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.

  15. On-chip microreactor system for the production of nano-emulsion loaded liposomes: towards targeted delivery of lipophilic drugs

    NARCIS (Netherlands)

    Langelaan, M.L.P.; Emmelkamp, J.; Segers, M.J.A.; Lenting, H.B.M.

    2011-01-01

    An on-chip microreactor system for the production of novel nano-biodevices is presented. This nano-biodevice consists of a nano-emulsion loaded with lipophilic drugs, entrapped in liposomes. These nano-biodevices can be equipped with targeting molecules for higher drug efficiency. The microreactor

  16. Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule.

    Science.gov (United States)

    2010-09-29

    The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health.

  17. Survey of metals on antimicrobial and deodorant agents in household Necessities; Mukikei kokinsei kakoseihin no shiyojittai

    Energy Technology Data Exchange (ETDEWEB)

    Kan, Teruo

    1999-11-01

    It measured the metal bearing quantity in household necessities in order to clarify use actual condition of the metal system drug. And, it tried the detection of the drug used from detected metal. Too there is the report until now in the investigation of the metallic element in household necessities. However, metals examined this time are silver and zinc, four of copper and aluminum that it says that it has the antimicrobial action and is Key element of inorganic system antimicrobial agent. And, it carried out the analysis by inductive coupling plasma emission analysis method, after the wet digestion of the sample was done. (NEDO)

  18. Batch-to-batch quality consistency evaluation of botanical drug products using multivariate statistical analysis of the chromatographic fingerprint.

    Science.gov (United States)

    Xiong, Haoshu; Yu, Lawrence X; Qu, Haibin

    2013-06-01

    Botanical drug products have batch-to-batch quality variability due to botanical raw materials and the current manufacturing process. The rational evaluation and control of product quality consistency are essential to ensure the efficacy and safety. Chromatographic fingerprinting is an important and widely used tool to characterize the chemical composition of botanical drug products. Multivariate statistical analysis has showed its efficacy and applicability in the quality evaluation of many kinds of industrial products. In this paper, the combined use of multivariate statistical analysis and chromatographic fingerprinting is presented here to evaluate batch-to-batch quality consistency of botanical drug products. A typical botanical drug product in China, Shenmai injection, was selected as the example to demonstrate the feasibility of this approach. The high-performance liquid chromatographic fingerprint data of historical batches were collected from a traditional Chinese medicine manufacturing factory. Characteristic peaks were weighted by their variability among production batches. A principal component analysis model was established after outliers were modified or removed. Multivariate (Hotelling T(2) and DModX) control charts were finally successfully applied to evaluate the quality consistency. The results suggest useful applications for a combination of multivariate statistical analysis with chromatographic fingerprinting in batch-to-batch quality consistency evaluation for the manufacture of botanical drug products.

  19. Analytical challenges and regulatory requirements for nasal drug products in europe and the u.s.

    Science.gov (United States)

    Trows, Sabrina; Wuchner, Klaus; Spycher, Rene; Steckel, Hartwig

    2014-04-11

    Nasal drug delivery can be assessed by a variety of means and regulatory agencies, e.g., the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published a set of guidelines and regulations proposing in vitro test methods for the characterization of nasal drug products. This article gives a summary of the FDA and EMA requirements regarding the determination of droplet size distribution (DSD), plume geometry, spray pattern and shot weights of solution nasal sprays and discusses the analytical challenges that can occur when performing these measurements. In order to support findings from the literature, studies were performed using a standard nasal spray pump and aqueous model formulations. The aim was to identify possible method-, device- and formulation-dependent influencing factors. The literature review, as well as the results from the studies show that DSD, plume geometry and spray pattern are influenced by, e.g., the viscosity of the solution, the design of the device and the actuation parameters, particularly the stroke length, actuation velocity and actuation force. The dominant factor influencing shot weights, however, is the adjustment of the actuation parameters, especially stroke length and actuation velocity. Consequently, for routine measurements assuring, e.g., the quality of a solution nasal spray or, for in vitro bioequivalence studies, the critical parameters, have to be identified and considered in method development in order to obtain reproducible and reliable results.

  20. Symbiotic Microbes from Marine Invertebrates: Driving a New Era of Natural Product Drug Discovery

    Directory of Open Access Journals (Sweden)

    Alix Blockley

    2017-10-01

    Full Text Available Invertebrates account for more than 89% of all extant organisms in the marine environment, represented by over 174,600 species (recorded to date. Such diversity is mirrored in (or more likely increased by the microbial symbionts associated with this group and in the marine natural products (or MNPs that they produce. Since the early 1950s over 20,000 MNPs have been discovered, including compounds produced by symbiotic bacteria, and the chemical diversity of compounds produced from marine sources has led to them being referred to as "blue gold" in the search for new drugs. For example, 80% of novel antibiotics stemming from the marine environment have come from Actinomycetes, many of which can be found associated with marine sponges, and compounds with anti-tumorigenic and anti-diabetic potential have also been isolated from marine symbionts. In fact, it has been estimated that marine sources formed the basis of over 50% of FDA-approved drugs between 1981 and 2002. In this review, we explore the diversity of marine microbial symbionts by examining their use as the producers of novel pharmaceutical actives, together with a discussion of the opportunities and constraints offered by “blue gold” drug discovery.

  1. Can Brazil play a more important role in global tuberculosis drug production? An assessment of current capacity and challenges.

    Science.gov (United States)

    Gemal, Andre; Keravec, Joel; Menezes, Alexandre; Trajman, Anete

    2013-03-27

    Despite the existence of effective treatment, tuberculosis is still a global public health issue. The World Health Organization recommends a six-month four-drug regimen in fixed-dose combination formulation to treat drug sensitive tuberculosis, and long course regimens with several second-line drugs to treat multi-drug resistant tuberculosis. To achieve the projected tuberculosis elimination goal by 2050, it will be essential to ensure a non-interrupted supply of quality-assured tuberculosis drugs. However, quality and affordable tuberculosis drug supply is still a significant challenge for National Tuberculosis Programs. Quality drug production requires a combination of complex steps. The first challenge is to guarantee the quality of tuberculosis active pharmaceutical ingredients, then ensure an adequate manufacturing process, according to international standards, to guarantee final product's safety, efficacy and quality. Good practices for storage, transport, distribution and quality control procedures must follow. In contrast to other high-burden countries, Brazil produces tuberculosis drugs through a strong network of public sector drug manufacturers regulated by a World Health Organization-certified national sanitary authority. The installed capacity for production surpasses the 71,000 needed treatments in the country. However, in order to be prepared to act as a global supplier, important bottlenecks are to be overcome. This article presents an in-depth analysis of the current status of production of tuberculosis drugs in Brazil and the bottlenecks and opportunities for the country to sustain national demand and play a role as a potential global supplier. Raw material and drug production, quality control, international certification and pre-qualification, political commitment and regulatory aspects are discussed, as well recommendations for tackling these bottlenecks. This discussion becomes more important as new drugs and regimens to treat tuberculosis are

  2. 76 FR 11330 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug...

    Science.gov (United States)

    2011-03-02

    ... Cosmetic Act and under the authority delegated to the Commissioner of Food and Drugs and redelegated to the.... * * * * * (b) * * * (6) No. 058829 for use of 100-mg or 1-g tablets in dogs and horses. * * * * * PART 558--NEW...

  3. Deodorants are the leading cause of allergic contact dermatitis to fragrance ingredients

    DEFF Research Database (Denmark)

    Heisterberg, Maria V; Menné, Torkil; Andersen, Klaus E

    2011-01-01

    Fragrances frequently cause contact allergy, and cosmetic products are the main causes of fragrance contact allergy. As the various products have distinctive forms of application and composition of ingredients, some product groups are potentially more likely to play a part in allergic reactions t...

  4. Modifying release characteristics from 3D printed drug-eluting products

    DEFF Research Database (Denmark)

    Boetker, Johan; Water, Jorrit; Aho, Johanna

    2016-01-01

    Abstract This work describes an approach to modify the release of active compound from a 3D printed model drug product geometry intended for flexible dosing and precision medication. The production of novel polylactic acid and hydroxypropyl methylcellulose based feed materials containing...... nitrofurantoin for 3D printing purposes is demonstrated. Nitrofurantoin, Metolose® and polylactic acid were successfully co-extruded with up to 40% Metolose® content, and subsequently 3D printed into model disk geometries (ø10 mm, h = 2 mm). Thermal analysis with differential scanning calorimetry and solid phase...... identification with Raman spectroscopy showed that nitrofurantoin remained in its original solid form during both hot-melt extrusion and subsequent 3D printing. Rheological measurements of the different compositions showed that the flow properties were sensitive to the amount of undissolved particles present...

  5. Natural products to improve quality of life targeting for colon drug delivery.

    Science.gov (United States)

    Kim, Hyunjo

    2012-03-01

    The colon is largely being investigated as a site for administration of protein and peptides, which are degraded by digestive enzymes in the upper GIT. Also for local diseases of the colon such as inflammatory bowel disease, colorectal cancer and ameobiasis, drug administration to the site of action can not only reduce the dose to be administered, but also decrease the side effects. Inflammatory Bowel Disease (IBD) such as Ulcerative colitis and Crohn's disease are characterized by chronic intestinal inflammation. Intestinal bacteria initiate the activation of intestinal inflammatory processes, which are mediated by pro-inflammatory cytokines and chemokine. Increased chemokine expression has also been observed in epithelial cells, endothelial cells, and smooth muscle cells. Future trials of specific agents capable of inhibiting chemokine synthesis and secretion or blocking chemokine-chemokine receptor interaction will be important to study in patients with ulcerative colitis and Crohn's disease. Many important bioactive compounds have been discovered from natural sources using bioactivity directed fractionation and isolation (BDFl) Continuing discovery has also been facilitated by the recent development of new bioassay methods. These bioactive compounds are mostly plant secondary metabolites, and many naturally occurring pure compounds have become medicines, dietary supplements, and other useful commercial products. The present review includes various approaches investigated for colon drug delivery and their site specificity. To achieve successful colonic delivery, a drug needs to be protected from absorption and the environment of the upper gastrointestinal tract and then be abruptly released into the proximal colon, which is considered the optimum site for colon targeted delivery of drugs.

  6. Particle shedding from peristaltic pump tubing in biopharmaceutical drug product manufacturing.

    Science.gov (United States)

    Saller, Verena; Matilainen, Julia; Grauschopf, Ulla; Bechtold-Peters, Karoline; Mahler, Hanns-Christian; Friess, Wolfgang

    2015-04-01

    In a typical manufacturing setup for biopharmaceutical drug products, the fill and dosing pump is placed after the final sterile filtration unit in order to ensure adequate dispensing accuracy and avoid backpressure peaks. Given the sensitivity of protein molecules, peristaltic pumps are often preferred over piston pumps. However, particles may be shed from the silicone tubing employed. In this study, particle shedding and a potential turbidity increase during peristaltic pumping of water and buffer were investigated using three types of commercially available silicone tubing. In the recirculates, mainly particles of around 200 nm next to a very small fraction of particles in the lower micrometer range were found. Using 3D laser scanning microscopy, surface roughness of the inner tubing surface was found to be a determining factor for particle shedding from silicone tubing. As the propensity toward particle shedding varied between tubing types and also cannot be concluded from manufacturer's specifications, individual testing with the presented methods is recommended during tubing qualification. Choosing low abrasive tubing can help to further minimize the very low particle counts to be expected in pharmaceutical drug products. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  7. A bibliometric analysis of scientific production on atypical antipsychotic drugs from Italy

    Science.gov (United States)

    López-Muñoz, Francisco; De Berardis, Domenico; Fornaro, Michele; Vellante, Federica; di Giannantonio, Massimo; Povedano-Montero, Francisco J; Póveda Fernández-Martín, Maria; Rubio, Gabriel; Álamo, Cecilio

    2017-01-01

    A bibliometric study of peer-reviewed scientific publications on atypical antipsychotic drugs (AADs) from Italy is herein presented. We selected the documents from Scopus database. We applied several bibliometric indicators of production and dispersion, including Price’s Law about the increase of scientific literature, and Bradford’s Law. We also calculated the participation index across different countries. The bibliometric data have also been correlated with some social and health data sourcing in Italy, such as total per capita expenditure on health and gross domestic expenditure. A total of 2949 original documents were published within the period 1972-2015. Our results state fulfilment of Price’s Law, with scientific production showing exponential growth (r=0.901, as against an r=0.838 after linear adjustment). The drugs most widely studied were clozapine (257 documents), risperidone (179), and olanzapine (172). Stratification into Bradford zones yielded a nucleus represented by the Journal of Clinical Psychopharmacology and Rivista di Psichiatria (58 articles, each one). A total of 1091 different journals were evaluated. The publications on AADs in Italy have undergone exponential growth over the studied period, which is in line with the progressively burgeoning on novel AAD releases. No evidence of saturation point was observed.

  8. Pharmaceutical quality of docetaxel generics versus originator drug product: a comparative analysis.

    Science.gov (United States)

    Vial, Jérôme; Cohen, Mélanie; Sassiat, Patrick; Thiébaut, Didier

    2008-07-01

    The aim of this study was to evaluate the quality of 31 commercially available generic formulations of docetaxel purchased in 14 countries by comparing their docetaxel content, impurity levels and pH versus those of the proprietary product Taxotere (Tx). Generic formulations were purchased in 14 countries in Asia, Africa, the Middle East and Latin America. Levels of docetaxel and impurities (chromatographic peaks above 0.05%) were obtained for each sample using reverse-phase liquid chromatography with ultraviolet detection. The pH of aqueous solutions of generic docetaxel formulations and Tx was also measured. A global evaluation of quality was conducted on each product using a multicriteria desirability analysis based on standards defined by the International Conference on Harmonisation guidelines and the US Pharmacopeia paclitaxel injection monograph. Most generic formulations contained a lower than expected amount of docetaxel and/or a high level of impurities: 21 generic docetaxel formulations had an average mass of docetaxel that was generic docetaxel formulations had a total impurity content of >3.0%, almost twice the level of impurities in Tx 20 mg. In total, 33 impurities not present in Tx were detected in the generic samples. Desirability analysis demonstrated that none of the generic docetaxel formulations had composition characteristics similar to those of Tx. This study demonstrated that from an analytical point of view, 90% of the generic docetaxel formulations evaluated contained insufficient active drug, high levels of impurities or both. This has the potential to affect both efficacy and safety of the drug.

  9. Challenges and strategies to facilitate formulation development of pediatric drug products: Safety qualification of excipients.

    Science.gov (United States)

    Buckley, Lorrene A; Salunke, Smita; Thompson, Karen; Baer, Gerri; Fegley, Darren; Turner, Mark A

    2018-02-05

    A public workshop entitled "Challenges and strategies to facilitate formulation development of pediatric drug products" focused on current status and gaps as well as recommendations for risk-based strategies to support the development of pediatric age-appropriate drug products. Representatives from industry, academia, and regulatory agencies discussed the issues within plenary, panel, and case-study breakout sessions. By enabling practical and meaningful discussion between scientists representing the diversity of involved disciplines (formulators, nonclinical scientists, clinicians, and regulators) and geographies (eg, US, EU), the Excipients Safety workshop session was successful in providing specific and key recommendations for defining paths forward. Leveraging orthogonal sources of data (eg. food industry, agro science), collaborative data sharing, and increased awareness of the existing sources such as the Safety and Toxicity of Excipients for Paediatrics (STEP) database will be important to address the gap in excipients knowledge needed for risk assessment. The importance of defining risk-based approaches to safety assessments for excipients vital to pediatric formulations was emphasized, as was the need for meaningful stakeholder (eg, patient, caregiver) engagement. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Natural products, an important resource for discovery of multitarget drugs and functional food for regulation of hepatic glucose metabolism.

    Science.gov (United States)

    Li, Jian; Yu, Haiyang; Wang, Sijian; Wang, Wei; Chen, Qian; Ma, Yanmin; Zhang, Yi; Wang, Tao

    2018-01-01

    Imbalanced hepatic glucose homeostasis is one of the critical pathologic events in the development of metabolic syndromes (MSs). Therefore, regulation of imbalanced hepatic glucose homeostasis is important in drug development for MS treatment. In this review, we discuss the major targets that regulate hepatic glucose homeostasis in human physiologic and pathophysiologic processes, involving hepatic glucose uptake, glycolysis and glycogen synthesis, and summarize their changes in MSs. Recent literature suggests the necessity of multitarget drugs in the management of MS disorder for regulation of imbalanced glucose homeostasis in both experimental models and MS patients. Here, we highlight the potential bioactive compounds from natural products with medicinal or health care values, and focus on polypharmacologic and multitarget natural products with effects on various signaling pathways in hepatic glucose metabolism. This review shows the advantage and feasibility of discovering multicompound-multitarget drugs from natural products, and providing a new perspective of ways on drug and functional food development for MSs.

  11. Adulteration of proprietary Chinese medicines and health products with undeclared drugs: experience of a tertiary toxicology laboratory in Hong Kong.

    Science.gov (United States)

    Ching, Chor Kwan; Chen, Sammy Pak Lam; Lee, Hencher Han Chih; Lam, Ying Hoo; Ng, Sau Wah; Chen, Mo Lung; Tang, Magdalene Huen Yin; Chan, Suzanne Suk San; Ng, Candy Wai Yan; Cheung, Jana Wing Lan; Chan, Tina Yee Ching; Lau, Nike Kwai Cheung; Chong, Yeow Kuan; Mak, Tony Wing Lai

    2018-01-01

    Proprietary Chinese medicines (pCMs) and health products, generally believed to be natural and safe, are gaining popularity worldwide. However, the safety of pCMs and health products has been severely compromised by the practice of adulteration. The current study aimed to examine the problem of adulteration of pCMs and health products in Hong Kong. The present study was conducted in a tertiary referral clinical toxicology laboratory in Hong Kong. All cases involving the use of pCMs or health products, which were subsequently confirmed to contain undeclared adulterants, from 2005 to 2015 were reviewed retrospectively. A total of 404 cases involving the use of 487 adulterated pCMs or health products with a total of 1234 adulterants were identified. The adulterants consisted of approved drugs, banned drugs, drug analogues and animal thyroid tissue. The six most common categories of adulterants detected were nonsteroidal anti-inflammatory drugs (17.7%), anorectics (15.3%), corticosteroids (13.8%), diuretics and laxatives (11.4%), oral antidiabetic agents (10.0%) and erectile dysfunction drugs (6.0%). Sibutramine was the most common adulterant (n = 155). The reported sources of these illicit products included over-the-counter drug stores, the internet and Chinese medicine practitioners. A significant proportion of patients (65.1%) had adverse effects attributable to these illicit products, including 14 severe and two fatal cases. Psychosis, iatrogenic Cushing syndrome and hypoglycaemia were the three most frequently encountered adverse effects. Adulteration of pCMs and health products with undeclared drugs poses severe health hazards. Public education and effective regulatory measures are essential to address the problem. © 2017 The British Pharmacological Society.

  12. On-site management of investigational products and drug delivery systems in conformity with Good Clinical Practices (GCPs).

    Science.gov (United States)

    Méthot, Julie; Brisson, Diane; Gaudet, Daniel

    2012-04-01

    Investigators and research teams participating in clinical trials have to deal with complex investigational products, study designs, and research environments. The emergence of new drug delivery systems and investigational products combining more than one drug and the development of biodrugs such as monoclonal antibodies, peptides, siRNA, and gene therapy to treat orphan or common diseases constitute a new challenge for investigators and clinical sites. We describe the requirements and challenges of drug management in conformity with Good Clinical Practices (GCPs) for investigators and sites participating in clinical trials. Review At all sites participating in clinical trials, standard operating procedures (SOPs) covering the critical path of drug and drug delivery systems management are required. All steps should be auditable, including reception, validation, storage, access, preparation, distribution, techniques of administration, use, return, and destruction of research products. Biodrugs require traceability and specific SOPs on the management of potential immune reactions. Investigational products must be stored under standard auditable conditions. The traceability of storage conditions (including temperature) requires these conditions to be monitored on a continuous basis. A dedicated space with restricted access limited to authorized qualified personnel facilitates the monitoring. The development of standardized, auditable settings and the application of dedicated, site-specific SOPs for the management of investigational products and drug delivery systems contribute to guarantee the compliance to GCP requirements.

  13. Fate and antibacterial potency of anticoccidial drugs and their main abiotic degradation products

    International Nuclear Information System (INIS)

    Hansen, Martin; Krogh, Kristine A.; Brandt, Asbjorn; Christensen, Jan H.; Halling-Sorensen, Bent

    2009-01-01

    The antibacterial potency of eight anticoccidial drugs was tested in a soil bacteria bioassay (pour plate method), EC 50 -values between 2.4 and 19.6 μM were obtained; however, one compound, nicarbazin exhibited an EC 50 -value above the maximum tested concentration (21 μM, 9.1 mg L -1 ). The potency of mixtures of two of the compounds, narasin and nicarbazin, was synergistic (more than additive) with 10-fold greater antibacterial potency of the mixture than can be explained by their individual EC 50 -values. The influence of pH, temperature, oxygen concentration and light on the transformation of robenidine and salinomycin was investigated. Robenidine was transformed by photolysis (DT 50 of 4.1 days) and was unstable at low pH (DT 50 of approximately 4 days); salinomycin was merely transformed at low pH, the latter into an unknown number of products. The antibacterial potency of the mixtures of transformation products of robenidine after photolysis and at low pH was comparable with that of the parent compound. Finally five photo-transformation products of robenidine were structural elucidated by accurate mass measurements, i-FIT values (isotopic pattern fit) and MS/MS fragmentation patterns. - Five photo-transformation products of robenidine were structural elucidated. This mixture was found to have similar antibacterial potency as the parent compound

  14. Fate and antibacterial potency of anticoccidial drugs and their main abiotic degradation products

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Martin [Section of Toxicology and Environmental Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark)], E-mail: mah@farma.ku.dk; Krogh, Kristine A. [Section of Toxicology and Environmental Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark); Brandt, Asbjorn [Section of Veterinary Medicines, Danish Medicines Agency, Axel Heides Gade 1, DK-2300 Copenhagen (Denmark); Christensen, Jan H. [Section of Soil and Environmental Chemistry, Department of Basic Sciences and Environment, Faculty of Life Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Frederiksberg (Denmark); Halling-Sorensen, Bent [Section of Toxicology and Environmental Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark)

    2009-02-15

    The antibacterial potency of eight anticoccidial drugs was tested in a soil bacteria bioassay (pour plate method), EC{sub 50}-values between 2.4 and 19.6 {mu}M were obtained; however, one compound, nicarbazin exhibited an EC{sub 50}-value above the maximum tested concentration (21 {mu}M, 9.1 mg L{sup -1}). The potency of mixtures of two of the compounds, narasin and nicarbazin, was synergistic (more than additive) with 10-fold greater antibacterial potency of the mixture than can be explained by their individual EC{sub 50}-values. The influence of pH, temperature, oxygen concentration and light on the transformation of robenidine and salinomycin was investigated. Robenidine was transformed by photolysis (DT{sub 50} of 4.1 days) and was unstable at low pH (DT{sub 50} of approximately 4 days); salinomycin was merely transformed at low pH, the latter into an unknown number of products. The antibacterial potency of the mixtures of transformation products of robenidine after photolysis and at low pH was comparable with that of the parent compound. Finally five photo-transformation products of robenidine were structural elucidated by accurate mass measurements, i-FIT values (isotopic pattern fit) and MS/MS fragmentation patterns. - Five photo-transformation products of robenidine were structural elucidated. This mixture was found to have similar antibacterial potency as the parent compound.

  15. Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014).

    Science.gov (United States)

    Gnanasakthy, Ari; DeMuro, Carla; Clark, Marci; Haydysch, Emily; Ma, Esprit; Bonthapally, Vijayveer

    2016-06-01

    To review the use of patient-reported outcome (PRO) data in medical product labeling granted by the US Food and Drug Administration (FDA) for new molecular entities and biologic license applications by the FDA Office of Hematology and Oncology Products (OHOP) between January 2010 and December 2014, to elucidate challenges faced by OHOP for approving PRO labeling, and to understand challenges faced by drug manufacturers to include PRO end points in oncology clinical trials. FDA Drug Approval Reports by Month were reviewed to obtain the number of new molecular entities and biologic license applications approved from 2010 to 2014. Drugs approved by the FDA OHOP during this period were selected for further review, focusing on brand and generic name; approval date; applicant; indication; PRO labeling describing treatment benefit, measures, end point status, and significant results; FDA reviewer feedback on PRO end points; and study design of registration trials. First in class, priority review, fast track, orphan drug, or accelerated approval status was retrieved for selected oncology drugs from 2011 to 2014. Descriptive analyses were performed by using Microsoft Excel 2010. Of 160 drugs approved by the FDA (2010-2014), 40 were approved by OHOP. Three (7.5%) of the 40 received PRO-related labeling (abiraterone acetate, ruxolitinib phosphate, and crizotinib). Compared with nononcology drugs (2011-2014), oncology drugs were more likely to be orphan and first in class. The majority of oncology drug reviews by FDA were fast track, priority, or accelerated. Although symptoms and functional decrements are common among patients with cancer, PRO labeling is rare in the United States, likely because of logistical hurdles and oncology study design. Recent developments within the FDA OHOP to capture PROs in oncology studies for the purpose of product labeling are encouraging. © 2016 by American Society of Clinical Oncology.

  16. Electrosynthesis methods and approaches for the preparative production of metabolites from parent drugs

    NARCIS (Netherlands)

    Gül, Turan; Bischoff, Rainer; Permentier, Hjalmar

    2015-01-01

    Identification of potentially toxic metabolites is important for drug discovery and development. Synthesis of drug metabolites is typically performed by organic synthesis or enzymatic methods, but is not always straightforward. Electrochemical (EC) methods are increasingly used to study drug

  17. Scaffold architecture and pharmacophoric properties of natural products and trade drugs: application in the design of natural product-based combinatorial libraries.

    Science.gov (United States)

    Lee, M L; Schneider, G

    2001-01-01

    Natural products were analyzed to determine whether they contain appealing novel scaffold architectures for potential use in combinatorial chemistry. Ring systems were extracted and clustered on the basis of structural similarity. Several such potential scaffolds for combinatorial chemistry were identified that are not present in current trade drugs. For one of these scaffolds a virtual combinatorial library was generated. Pharmacophoric properties of natural products, trade drugs, and the virtual combinatorial library were assessed using a self-organizing map. Obviously, current trade drugs and natural products have several topological pharmacophore patterns in common. These features can be systematically explored with selected combinatorial libraries based on a combination of natural product-derived and synthetic molecular building blocks.

  18. DNA sequence analyses of blended herbal products including synthetic cannabinoids as designer drugs.

    Science.gov (United States)

    Ogata, Jun; Uchiyama, Nahoko; Kikura-Hanajiri, Ruri; Goda, Yukihiro

    2013-04-10

    In recent years, various herbal products adulterated with synthetic cannabinoids have been distributed worldwide via the Internet. These herbal products are mostly sold as incense, and advertised as not for human consumption. Although their labels indicate that they contain mixtures of several potentially psychoactive plants, and numerous studies have reported that they contain a variety of synthetic cannabinoids, their exact botanical contents are not always clear. In this study, we investigated the origins of botanical materials in 62 Spice-like herbal products distributed on the illegal drug market in Japan, by DNA sequence analyses and BLAST searches. The nucleotide sequences of four regions were analyzed to identify the origins of each plant species in the herbal mixtures. The sequences of "Damiana" (Turnera diffusa) and Lamiaceae herbs (Mellissa, Mentha and Thymus) were frequently detected in a number of products. However, the sequences of other plant species indicated on the packaging labels were not detected. In a few products, DNA fragments of potent psychotropic plants were found, including marijuana (Cannabis sativa), "Diviner's Sage" (Salvia divinorum) and "Kratom" (Mitragyna speciosa). Their active constituents were also confirmed using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), although these plant names were never indicated on the labels. Most plant species identified in the products were different from the plants indicated on the labels. The plant materials would be used mainly as diluents for the psychoactive synthetic compounds, because no reliable psychoactive effects have been reported for most of the identified plants, with the exception of the psychotropic plants named above. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. 77 FR 12059 - Using Innovative Technologies and Other Conditions of Safe Use To Expand Which Drug Products Can...

    Science.gov (United States)

    2012-02-28

    ...] Using Innovative Technologies and Other Conditions of Safe Use To Expand Which Drug Products Can Be... over-the- counter or OTC products) can be purchased by consumers in pharmacies, supermarkets, and other retail establishments without the need for a prescription. Currently, consumers can purchase...

  20. Evaluation of Container Closure System Integrity for Frozen Storage Drug Products.

    Science.gov (United States)

    Nieto, Alejandra; Roehl, Holger; Brown, Helen; Nikoloff, Jonas; Adler, Michael; Mahler, Hanns-Christian

    2016-01-01

    Sometimes, drug product for parenteral administration is stored in a frozen state (e.g., -20 °C or -80 °C), particularly during early stages of development of some biotech molecules in order to provide sufficient stability. Shipment of frozen product could potentially be performed in the frozen state, yet possibly at different temperatures, for example, using dry ice (-80 °C). Container closure systems of drug products usually consist of a glass vial, rubber stopper, and an aluminum crimped cap. In the frozen state, the glass transition temperature (Tg) of commonly used rubber stoppers is between -55 and -65 °C. Below their Tg, rubber stoppers are known to lose their elastic properties and become brittle, and thus potentially fail to maintain container closure integrity in the frozen state. Leaks during frozen temperature storage and transportation are likely to be transient, yet, can possibly risk container closure integrity and lead to microbial contamination. After thawing, the rubber stopper is supposed to re-seal the container closure system. Given the transient nature of the possible impact on container closure integrity in the frozen state, typical container closure integrity testing methods (used at room temperature conditions) are unable to evaluate and thus confirm container closure integrity in the frozen state. Here we present the development of a novel method (thermal physical container closure integrity) for direct assessment of container closure integrity by a physical method (physical container closure integrity) at frozen conditions, using a modified He leakage test. In this study, different container closure systems were evaluated with regard to physical container closure integrity in the frozen state to assess the suitability of vial/stopper combinations and were compared to a gas headspace method. In summary, the thermal physical container closure integrity He leakage method was more sensitive in detecting physical container closure

  1. The Use of Herbal Drugs in Organic Animal Production: The Case of Ethnoveterinary Medicine in Central Anatolia Region

    Directory of Open Access Journals (Sweden)

    Çağrı Çağlar Sinmez

    2017-12-01

    Full Text Available Organic animal production is a natural breeding system in which animal health is protected by giving priority to alternative medicines and treatment as needed by applying appropriate management and feeding methods based on the physiological requirements of animals. Increasing numbers of strains resistant to antibiotics and antiparasitic drugs used in animal breeding have brought about the search for alternative herbal remedies that lead to drug residues in animal products and lead to important health problems in people consuming these products. In this study, it was aimed to evaluate the therapeutic and protective effects of herbal drugs used in organic animal production in ethnoveterinary medicine in the Central Anatolia Region. The material of the study collected as written and declared facts as well as visual data were obtained from animal breeders in the Central Anatolia Region. The results indicated that 30 herbal drugs were used for the treatment of internal diseases, surgical diseases, obstetric and gynecological problems and parasitic diseases in cattle, sheep, horse, poultry, bee, and dog species. Based on the evaluation of the facts that the use of all kinds of synthetic drugs, especially antibiotics, is prohibited or restricted in organic livestock, it can be said that natural herbal drugs instead of artificial substances will provide positive contributions in the protection and treatment of herd health.

  2. Preclinical safety and efficacy of a new recombinant FIX drug product for treatment of hemophilia B.

    Science.gov (United States)

    Dietrich, Barbara; Schiviz, Alexandra; Hoellriegl, Werner; Horling, Frank; Benamara, Karima; Rottensteiner, Hanspeter; Turecek, Peter L; Schwarz, Hans Peter; Scheiflinger, Friedrich; Muchitsch, Eva-Maria

    2013-11-01

    Baxter has developed a new recombinant factor IX (rFIX) drug product (BAX326) for treating patients with hemophilia B, or congenital FIX deficiency. An extensive preclinical program evaluated the pharmacokinetics, efficacy, and safety of BAX326 in different species. The efficacy of BAX326 was tested in three mouse models of primary pharmacodynamics: tail-tip bleeding, carotid occlusion, and thrombelastography. The pharmacokinetics was evaluated after a single intravenous bolus injection in mice, rats, and macaques. Toxicity was assessed in rats and macaques, safety pharmacology in rabbits and macaques, and immunogenicity in mice. BAX326 was shown to be efficacious in all three primary pharmacodynamic studies (P ≤ 0.0076). Hemostatic efficacy was dose related and similar for the three lots tested. Pharmacokinetic results showed that rFIX activity and rFIX antigen concentrations declined in a bi-phasic manner, similar to a previously licensed rFIX product. BAX326 was well tolerated in rabbits and macaques at all dose levels; no thrombogenic events and no adverse clinical, respiratory, or cardiovascular effects occurred. BAX326 was also shown to have a similar immunogenicity profile to the comparator rFIX product in mice. These results demonstrate that BAX326 has a favorable preclinical safety and efficacy profile, predictive of a comparable effect to that of the previously licensed rFIX in humans.

  3. Food and Drug Administration process validation activities to support 99Mo production at Sandia National Laboratories

    International Nuclear Information System (INIS)

    McDonald, M.J.; Bourcier, S.C.; Talley, D.G.

    1997-01-01

    Prior to 1989 99 Mo was produced in the US by a single supplier, Cintichem Inc., Tuxedo, NY. Because of problems associated with operating its facility, in 1989 Cintichem elected to decommission the facility rather than incur the costs for repair. The demise of the 99 Mo capability at Cintichem left the US totally reliant upon a single foreign source, Nordion International, located in Ottawa Canada. In 1992 the DOE purchased the Cintichem 99 Mo Production Process and Drug Master File (DMF). In 1994 the DOE funded Sandia National Laboratories (SNL) to produce 99 Mo. Although Cintichem produced 99 Mo and 99m Tc generators for many years, there was no requirement for process validation which is now required by the Food and Drug Administration (FDA). In addition to the validation requirement, the requirements for current Good manufacturing Practices were codified into law. The purpose of this paper is to describe the process validation being conducted at SNL for the qualification of SNL as a supplier of 99 Mo to US pharmaceutical companies

  4. Production methodologies of polymeric and hydrogel particles for drug delivery applications.

    Science.gov (United States)

    Lima, Ana Catarina; Sher, Praveen; Mano, João F

    2012-02-01

    Polymeric particles are ideal vehicles for controlled delivery applications due to their ability to encapsulate a variety of substances, namely low- and high-molecular mass therapeutics, antigens or DNA. Micro and nano scale spherical materials have been developed as carriers for therapies, using appropriated methodologies, in order to achieve a prolonged and controlled drug administration. This paper reviews the methodologies used for the production of polymeric micro/nanoparticles. Emulsions, phase separation, spray drying, ionic gelation, polyelectrolyte complexation and supercritical fluids precipitation are all widely used processes for polymeric micro/nanoencapsulation. This paper also discusses the recent developments and patents reported in this field. Other less conventional methodologies are also described, such as the use of superhydrophobic substrates to produce hydrogel and polymeric particulate biomaterials. Polymeric drug delivery systems have gained increased importance due to the need for improving the efficiency and versatility of existing therapies. This allows the development of innovative concepts that could create more efficient systems, which in turn may address many healthcare needs worldwide. The existing methods to produce polymeric release systems have some critical drawbacks, which compromise the efficiency of these techniques. Improvements and development of new methodologies could be achieved by using multidisciplinary approaches and tools taken from other subjects, including nanotechnologies, biomimetics, tissue engineering, polymer science or microfluidics.

  5. Performance-enhancing drugs: design and production of redirected chimeric antigen receptor (CAR) T cells.

    Science.gov (United States)

    Levine, B L

    2015-03-01

    Performance enhancement of the immune system can now be generated through ex vivo gene modification of T cells in order to redirect native specificity to target tumor antigens. This approach combines the specificity of antibody therapy, the expanded response of cellular therapy and the memory activity of vaccine therapy. Recent clinical trials of chimeric antigen receptor (CAR) T cells directed toward CD19 as a stand-alone therapy have shown sustained complete responses in patients with acute lymphoblastic leukemia and chronic lymphocytic leukemia. As these drug products are individually derived from a patient's own cells, a different manufacturing approach is required for this kind of personalized therapy compared with conventional drugs. Key steps in the CAR T-cell manufacturing process include the selection and activation of isolated T cells, transduction of T cells to express CARs, ex vivo expansion of modified T cells and cryopreservation in infusible media. In this review, the steps involved in isolating, genetically modifying and scaling-out the CAR T cells for use in a clinical setting are described in the context of in-process and release testing and regulatory standards.

  6. 76 FR 72617 - Animal Drugs, Feeds, and Related Products; Eprinomectin; N-Methyl-2-Pyrrolidone

    Science.gov (United States)

    2011-11-25

    ... (NMP), is a carcinogen. As required by section 512(d)(1)(I) of the Federal Food, Drug, and Cosmetic Act... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 500, 522, and...-Pyrrolidone AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug...

  7. Antibacterial drugs in products originating from aquaculture: assessing the risks to public welfare

    Directory of Open Access Journals (Sweden)

    G. RIGOS

    2010-02-01

    Full Text Available As aquaculture expands to meet human demand and compensate for pessimistic forecasts of fisheries catches, usage of antibacterial agents to combat or forestall bacterial diseases is still a necessity, although effective vaccines and improved hygiene have aided drastically to this battle. The hazards for the consumer perspective arising from the imprudent use of such chemicals can be detrimental especially if the residues persist above legal tolerance. These may include selection and dissemination of resistant bacteria, disruption of the colonization barrier in the human intestinal flora and allergic reactions. In cases that unlawful drugs reached the consumer via consumption of aquatic products, human health may be jeopardized even further. The present review article assesses these risks on human health.

  8. [Patented photobioreactor to commercial production of new drugs and nutraceuticals from microalgae].

    Science.gov (United States)

    Talbierz, Szymon; Kujawska, Natalia; Latała, Adam

    2012-01-01

    Microalgae - microscopic photosynthetic plants are an inexhaustible source of compounds with potential pharmaceutical applications. However, the development of microalgal biotechnology in particular for the production of new drugs and nutraceuticals has been slowed by the limited growth performance of algae in industrial photobioreactors. This is due to low light intensity, necessary for photosynthesis, which causes growth of algae. Flat-Plate photobioreactor with a solar-tracker system which is reported to protect with the Patent Office of RP enables optimal positioning of culture vessel to the direction of the sun's rays and thus can increase the efficiency of biomass growth (by 30%) and lipid content, compared with photobioreactors without it. The use of the invention in industrial plants can significantly contribute to lower costs and make all the technology more profitable.

  9. Gastrointestinal Motility Variation and Implications for Plasma Level Variation: Oral Drug Products.

    Science.gov (United States)

    Talattof, Arjang; Price, Judy C; Amidon, Gordon L

    2016-02-01

    The oral route of administration is still by far the most ubiquitous method of drug delivery. Development in this area still faces many challenges due to the complexity and inhomogeneity of the gastrointestinal environment. In particular, dosing unpredictably relative to motility phase means the gastrointestinal environment is a random variable within a defined range. Here, we present a mass balance analysis that captures this variation and highlights the effects of gastrointestinal motility, exploring what impacts it ultimately has on plasma levels and the relationship to bioequivalence for high solubility products with both high and low permeability (BCS I and III). Motility-dependent compartmental absorption and transit (MDCAT) mechanistic analysis is developed to describe the underlying fasted state cyclical motility and how the contents of the gastrointestinal tract are propelled.

  10. Identification of risk products for fragrance contact allergy: a case-referent study based on patients' histories.

    Science.gov (United States)

    Johansen, J D; Andersen, T F; Kjøller, M; Veien, N; Avnstorp, C; Andersen, K E; Menné, T

    1998-06-01

    Fragrances are the first or second most common cause of contact allergy in dermatitis patients. The aim of this study was to identify risk products for fragrance contact allergy. The design was a case-control study with a case group of 78 fragrance-mix-positive eczema patients and two control groups, one consisting of 1,279 subjects selected as a random sample of the general population and the other consisting of 806 fragrance-mix-negative eczema patients. The identification of risk products was based on the patients' histories of rash to scented products. Analysis of the associations between first-time rash caused by different specified product categories and fragrance mix sensitivity was performed using logistic regression. It was found that first-time rash caused by deodorant sprays and/or perfumes were related to fragrance contact allergy in a comparison with both control groups. The risk (odds ratio) of being diagnosed as fragrance allergic was 2.3 to 2.9 greater in cases of a history of first-time rash to deodorant sprays and 3.3 to 3.4 greater in cases of a history of rash to perfumes than if no such history were present. First-time rash to cleansing agents, deodorant sticks, or hand lotions was also statistically significant but only in comparison with one of the control groups. Safety evaluation of fragrance materials used in perfumes and deodorant sprays should be performed with special attention.

  11. Summary report of PQRI Workshop on Nanomaterial in Drug Products: current experience and management of potential risks.

    Science.gov (United States)

    Bartlett, Jeremy A; Brewster, Marcus; Brown, Paul; Cabral-Lilly, Donna; Cruz, Celia N; David, Raymond; Eickhoff, W Mark; Haubenreisser, Sabine; Jacobs, Abigail; Malinoski, Frank; Morefield, Elaine; Nalubola, Ritu; Prud'homme, Robert K; Sadrieh, Nakissa; Sayes, Christie M; Shahbazian, Hripsime; Subbarao, Nanda; Tamarkin, Lawrence; Tyner, Katherine; Uppoor, Rajendra; Whittaker-Caulk, Margaret; Zamboni, William

    2015-01-01

    At the Product Quality Research Institute (PQRI) Workshop held last January 14-15, 2014, participants from academia, industry, and governmental agencies involved in the development and regulation of nanomedicines discussed the current state of characterization, formulation development, manufacturing, and nonclinical safety evaluation of nanomaterial-containing drug products for human use. The workshop discussions identified areas where additional understanding of material attributes, absorption, biodistribution, cellular and tissue uptake, and disposition of nanosized particles would continue to inform their safe use in drug products. Analytical techniques and methods used for in vitro characterization and stability testing of formulations containing nanomaterials were discussed, along with their advantages and limitations. Areas where additional regulatory guidance and material characterization standards would help in the development and approval of nanomedicines were explored. Representatives from the US Food and Drug Administration (USFDA), Health Canada, and European Medicines Agency (EMA) presented information about the diversity of nanomaterials in approved and newly developed drug products. USFDA, Health Canada, and EMA regulators discussed the applicability of current regulatory policies in presentations and open discussion. Information contained in several of the recent EMA reflection papers was discussed in detail, along with their scope and intent to enhance scientific understanding about disposition, efficacy, and safety of nanomaterials introduced in vivo and regulatory requirements for testing and market authorization. Opportunities for interaction with regulatory agencies during the lifecycle of nanomedicines were also addressed at the meeting. This is a summary of the workshop presentations and discussions, including considerations for future regulatory guidance on drug products containing nanomaterials.

  12. 76 FR 36307 - Guidance for Industry on Topical Acne Drug Products for Over-the-Counter Human Use-Revision of...

    Science.gov (United States)

    2011-06-22

    .... FDA-2011-D-0404] Guidance for Industry on Topical Acne Drug Products for Over-the- Counter Human Use... entities entitled ``Topical Acne Drug Products for Over-the-Counter Human Use--Revision of Labeling and... recognized as safe and effective (GRASE) active ingredient in over-the-counter (OTC) topical acne drug...

  13. Performance test of deodorants for ammonia gas; Ammonia gas ni taisuru dasshuzai no seino kentei ni kansuru kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    Yano, H.; Hashimoto, S.; Yonemura, S. [Shimizu Corp., Tokyo (Japan); Shoda, M. [Tokyo Institute of Technology, Tokyo (Japan)

    1998-01-10

    This paper presents the results of performance tests of various kinds of adsorbents by static and dynamic adsorption methods to select the optimum deodorant (adsorbent) for ammonia gas (NH3). In the performance test of the static adsorption method, the amounts of NH3 adsorbed by 21 kinds of adsorbents including physical and chemical adsorbents were measure. The amounts adsorbed physical adsorbent No. 6, chemical adsorbents Nos. 18, 19 and 20 which showed higher adsorption ability were 0.0160g/g, 0.0284g/g, 0.0250g/g, and 0.0249g/g respectively at 30degC under equilibrium pressure of 50 mmHg. All of the adsorbent showed in Freundlich`s adsorption isotherm for NH3. Although the correlation between specific area, pore volume, mean pore radius, pH each adsorbent and the amount of adsorbed were tried, the correlation between the pH and the amount of NH3 adsorbed was significant. This suggests that the pH is a proper criterion for selection for adsorbents. The performance test of the dynamic adsorption method, was conducted for adsorbents Nos. 6, 18, 19 and 20 above-mentioned. The 10% breakthrough time was compared as the performance index. The breakthrough time of the adsorbent which the amount adsorbed was large was long but the breakthrough time was not proportional to the amount adsorbed. These results suggest that the performance test only by the static adsorption method is insufficient and that the breakthrough time test by the dynamic adsorption method is essential. 13 refs., 10 figs., 4 tabs.

  14. Integration of in vitro biorelevant dissolution and in silico PBPK model of carvedilol to predict bioequivalence of oral drug products.

    Science.gov (United States)

    Ibarra, Manuel; Valiante, Cristian; Sopeña, Patricia; Schiavo, Alejandra; Lorier, Marianela; Vázquez, Marta; Fagiolino, Pietro

    2018-06-15

    Bioequivalence implementation in developing countries where a high proportion of similar drug products are being marketed has found several obstacles, impeding regulatory agencies to move forward with this policy. Biopharmaceutical quality of these products, several of which are massively prescribed, remains unknown. In this context, an in vitro-in silico-in vivo approach is proposed as a mean to screen product performance and target specific formulations for bioequivalence assessment. By coupling in vitro biorelevant dissolution testing in USP-4 Apparatus (flow-through cell) with physiologically-based pharmacokinetic (PBPK) modeling in PK-Sim® software (Bayer, Germany), the performance of seven similar products of carvedilol tablets containing 25 mg available in the Uruguayan market were compared with the brand-name drug Dilatrend®. In silico simulations for Dilatrend® were compared with published results of bioequivalence studies performed in fasting conditions allowing model development through a learning and confirming process. Single-dose pharmacokinetic profiles were then simulated for the brand-name drug and two similar drug products selected according to in vitro observations, in a virtual Caucasian population of 1000 subjects (50% male, aged between 18 and 50 years with standard body-weights). Population bioequivalence ratios were estimated revealing that in vitro differences in drug release would have a major impact in carvedilol maximum plasma concentration, leading to a non-bioequivalence outcome. Predictions support the need to perform in vivo bioequivalence for these products of extensive use. Application of the in vitro-in silico-in vivo approach stands as an interesting alternative to tackle and reduce drug product variability in biopharmaceutical quality. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. 21 CFR 212.71 - What actions must I take if a batch of PET drug product does not conform to specifications?

    Science.gov (United States)

    2010-04-01

    ... PRACTICE FOR POSITRON EMISSION TOMOGRAPHY DRUGS (Eff. 12-12-2011) Finished Drug Product Controls and..., operations, records, complaints, and any other relevant sources of information concerning the nonconforming...

  16. Production of peptides as generic drugs: a patent landscape of octreotide.

    Science.gov (United States)

    Sabatino, Giuseppina; Guryanov, Ivan; Rombecchi, Andrea; Zanon, Jacopo; Ricci, Antonio; Cabri, Walter; Papini, Anna Maria; Rovero, Paolo

    2016-01-01

    New low-cost strategies and enhancement of the already described methods to manufacture peptide molecules on an industrial scale are highly requested, particularly for peptides such as octreotide, which, along with goserelin and leuprolide, dominate the global peptide market. A number of patents related to the production of octreotide can be found, concerning both solution and solid-phase synthesis. Thus, there is a need to revise the existing synthetic approaches in order to organize them in a more comprehensible way. The octreotide patent landscape could help improvement of the methods for manufacturing of octreotide in industrial scale, leading to the appearance of innovative approaches. The pharmaceutical value of octreotide can be seen from its high market percentage among other peptide drugs. The complex chemical structure of octreotide represents the main challenge for its industrial production. Two synthetic steps are crucial in the preparation of octreotide: (i) threoninol attachment or on resin formation working in solid-phase and (ii) disulphide bond formation to achieve cyclic structure. Analysis of various patents filed to date allows us to see the trend in simplification of the synthetic approaches from the labor intensive syntheses in solution to the more versatile and rapid solid-phase methods.

  17. Life cycle of medical product rules issued by the US Food and Drug Administration.

    Science.gov (United States)

    Hwang, Thomas J; Avorn, Jerry; Kesselheim, Aaron S

    2014-08-01

    The US Food and Drug Administration (FDA) uses rulemaking as one of its primary tools to protect the public health and implement laws enacted by Congress and the president. Because of the many effects that these rules have on social welfare and the economy, the FDA and other executive agencies receive input from the executive branch, the public, and in some cases, the courts, during the process of rulemaking. In this article, we examine the life cycle of FDA regulations concerning medical products and review notable features of the rulemaking process. The current system grants substantial opportunities for diverse stakeholders to participate in and influence how rules are written and implemented. However, the duration, complexity, and adversarial qualities of the rulemaking process can hinder the FDA's ability to achieve its policy and public health goals. There is considerable variation in the level of transparency at different stages in the process, ranging from freely accessible public comments to undisclosed internal agency deliberations. In addition, significant medical product rules are associated with lengthy times to finalization, in some cases for unclear reasons. We conclude by identifying potential areas for reform on the basis of transparency and efficiency. Copyright © 2014 by Duke University Press.

  18. Klebsiella pneumoniae yfiRNB operon affects biofilm formation, polysaccharide production and drug susceptibility.

    Science.gov (United States)

    Huertas, Mónica G; Zárate, Lina; Acosta, Iván C; Posada, Leonardo; Cruz, Diana P; Lozano, Marcela; Zambrano, María M

    2014-12-01

    Klebsiella pneumoniae is an opportunistic pathogen important in hospital-acquired infections, which are complicated by the rise of drug-resistant strains and the capacity of cells to adhere to surfaces and form biofilms. In this work, we carried out an analysis of the genes in the K. pneumoniae yfiRNB operon, previously implicated in biofilm formation. The results indicated that in addition to the previously reported effect on type 3 fimbriae expression, this operon also affected biofilm formation due to changes in cellulose as part of the extracellular matrix. Deletion of yfiR resulted in enhanced biofilm formation and an altered colony phenotype indicative of cellulose overproduction when grown on solid indicator media. Extraction of polysaccharides and treatment with cellulase were consistent with the presence of cellulose in biofilms. The enhanced cellulose production did not, however, correlate with virulence as assessed using a Caenorhabditis elegans assay. In addition, cells bearing mutations in genes of the yfiRNB operon varied with respect to the WT control in terms of susceptibility to the antibiotics amikacin, ciprofloxacin, imipenem and meropenem. These results indicated that the yfiRNB operon is implicated in the production of exopolysaccharides that alter cell surface characteristics and the capacity to form biofilms--a phenotype that does not necessarily correlate with properties related with survival, such as resistance to antibiotics. © 2014 The Authors.

  19. The secondary drying and the fate of organic solvents for spray dried dispersion drug product.

    Science.gov (United States)

    Hsieh, Daniel S; Yue, Hongfei; Nicholson, Sarah J; Roberts, Daniel; Schild, Richard; Gamble, John F; Lindrud, Mark

    2015-05-01

    To understand the mechanisms of secondary drying of spray-dried dispersion (SDD) drug product and establish a model to describe the fate of organic solvents in such a product. The experimental approach includes characterization of the SDD particles, drying studies of SDD using an integrated weighing balance and mass spectrometer, and the subsequent generation of the drying curve. The theoretical approach includes the establishment of a Fickian diffusion model. The kinetics of solvent removal during secondary drying from the lab scale to a bench scale follows Fickian diffusion model. Excellent agreement is obtained between the experimental data and the prediction from the modeling. The diffusion process is dependent upon temperature. The key to a successful scale up of the secondary drying is to control the drying temperature. The fate of primary solvents including methanol and acetone, and their potential impurity such as benzene can be described by the Fickian diffusion model. A mathematical relationship based upon the ratio of diffusion coefficient was established to predict the benzene concentration from the fate of the primary solvent during the secondary drying process.

  20. Analysis of Intra- and Intersubject Variability in Oral Drug Absorption in Human Bioequivalence Studies of 113 Generic Products.

    Science.gov (United States)

    Sugihara, Masahisa; Takeuchi, Susumu; Sugita, Masaru; Higaki, Kazutaka; Kataoka, Makoto; Yamashita, Shinji

    2015-12-07

    high intrasubject variability in oral drug absorption. This information is of importance to design the human BE study for oral drug products containing APIs with a risk of large intrasubject variability in oral absorption.

  1. Limitations of drug registries to evaluate orphan medicinal products for the treatment of lysosomal storage disorders

    NARCIS (Netherlands)

    Hollak, Carla E. M.; Aerts, Johannes M. F. G.; Aymé, Ségolène; Manuel, Jeremy

    2011-01-01

    Orphan drugs are often approved under exceptional circumstances, requiring submission of additional data on safety and effectiveness through registries. These registries are mainly focused on one drug only and data is frequently incomplete. Some registries also address phenotypic heterogeneity and

  2. A thiopurine drug inhibits West Nile virus production in cell culture, but not in mice.

    Science.gov (United States)

    Lim, Pei-Yin; Keating, Julie A; Hoover, Spencer; Striker, Rob; Bernard, Kristen A

    2011-01-01

    Many viruses within the Flavivirus genus cause significant disease in humans; however, effective antivirals against these viruses are not currently available. We have previously shown that a thiopurine drug, 6-methylmercaptopurine riboside (6MMPr), inhibits replication of distantly related viruses within the Flaviviridae family in cell culture, including bovine viral diarrhea virus and hepatitis C virus replicon. Here we further examined the potential antiviral effect of 6MMPr on several diverse flaviviruses. In cell culture, 6MMPr inhibited virus production of yellow fever virus, dengue virus-2 (DENV-2) and West Nile virus (WNV) in a dose-dependent manner, and DENV-2 was significantly more sensitive to 6MMPr treatment than WNV. We then explored the use of 6MMPr as an antiviral against WNV in an immunocompetent mouse model. Once a day treatment of mice with 0.5 mg 6MMPr was just below the toxic dose in our mouse model, and this dose was used in subsequent studies. Mice were treated with 6MMPr immediately after subcutaneous inoculation with WNV for eight consecutive days. Treatment with 6MMPr exacerbated weight loss in WNV-inoculated mice and did not significantly affect mortality. We hypothesized that 6MMPr has low bioavailability in the central nervous system (CNS) and examined the effect of pre-treatment with 6MMPr on viral loads in the periphery and CNS. Pre-treatment with 6MMPr had no significant effect on viremia or viral titers in the periphery, but resulted in significantly higher viral loads in the brain, suggesting that the effect of 6MMPr is tissue-dependent. In conclusion, despite being a potent inhibitor of flaviviruses in cell culture, 6MMPr was not effective against West Nile disease in mice; however, further studies are warranted to reduce the toxicity and/or improve the bioavailability of this potential antiviral drug.

  3. A thiopurine drug inhibits West Nile virus production in cell culture, but not in mice.

    Directory of Open Access Journals (Sweden)

    Pei-Yin Lim

    Full Text Available Many viruses within the Flavivirus genus cause significant disease in humans; however, effective antivirals against these viruses are not currently available. We have previously shown that a thiopurine drug, 6-methylmercaptopurine riboside (6MMPr, inhibits replication of distantly related viruses within the Flaviviridae family in cell culture, including bovine viral diarrhea virus and hepatitis C virus replicon. Here we further examined the potential antiviral effect of 6MMPr on several diverse flaviviruses. In cell culture, 6MMPr inhibited virus production of yellow fever virus, dengue virus-2 (DENV-2 and West Nile virus (WNV in a dose-dependent manner, and DENV-2 was significantly more sensitive to 6MMPr treatment than WNV. We then explored the use of 6MMPr as an antiviral against WNV in an immunocompetent mouse model. Once a day treatment of mice with 0.5 mg 6MMPr was just below the toxic dose in our mouse model, and this dose was used in subsequent studies. Mice were treated with 6MMPr immediately after subcutaneous inoculation with WNV for eight consecutive days. Treatment with 6MMPr exacerbated weight loss in WNV-inoculated mice and did not significantly affect mortality. We hypothesized that 6MMPr has low bioavailability in the central nervous system (CNS and examined the effect of pre-treatment with 6MMPr on viral loads in the periphery and CNS. Pre-treatment with 6MMPr had no significant effect on viremia or viral titers in the periphery, but resulted in significantly higher viral loads in the brain, suggesting that the effect of 6MMPr is tissue-dependent. In conclusion, despite being a potent inhibitor of flaviviruses in cell culture, 6MMPr was not effective against West Nile disease in mice; however, further studies are warranted to reduce the toxicity and/or improve the bioavailability of this potential antiviral drug.

  4. Nature is the best source of anti-inflammatory drugs: indexing natural products for their anti-inflammatory bioactivity.

    Science.gov (United States)

    Aswad, Miran; Rayan, Mahmoud; Abu-Lafi, Saleh; Falah, Mizied; Raiyn, Jamal; Abdallah, Ziyad; Rayan, Anwar

    2018-01-01

    The aim was to index natural products for less expensive preventive or curative anti-inflammatory therapeutic drugs. A set of 441 anti-inflammatory drugs representing the active domain and 2892 natural products representing the inactive domain was used to construct a predictive model for bioactivity-indexing purposes. The model for indexing the natural products for potential anti-inflammatory activity was constructed using the iterative stochastic elimination algorithm (ISE). ISE is capable of differentiating between active and inactive anti-inflammatory molecules. By applying the prediction model to a mix set of (active/inactive) substances, we managed to capture 38% of the anti-inflammatory drugs in the top 1% of the screened set of chemicals, yielding enrichment factor of 38. Ten natural products that scored highly as potential anti-inflammatory drug candidates are disclosed. Searching the PubMed revealed that only three molecules (Moupinamide, Capsaicin, and Hypaphorine) out of the ten were tested and reported as anti-inflammatory. The other seven phytochemicals await evaluation for their anti-inflammatory activity in wet lab. The proposed anti-inflammatory model can be utilized for the virtual screening of large chemical databases and for indexing natural products for potential anti-inflammatory activity.

  5. 76 FR 36133 - Draft Guidances for Industry and Food and Drug Administration Staff: Classification of Products...

    Science.gov (United States)

    2011-06-21

    ... Action'' in the Definition of Device Under Section 201(h) of the Federal Food, Drug, and Cosmetic Act... the Term 'Chemical Action' in the Definition of Device Under Section 201(h) of the Federal Food, Drug... statutory definitions for these terms set forth in sections 201(g) and 201(h) of the Federal Food, Drug, and...

  6. New Insights on Degumming and Bleaching Process Parameters on The Formation of 3-Monochloropropane-1,2-Diol Esters and Glycidyl Esters in Refined, Bleached, Deodorized Palm Oil.

    Science.gov (United States)

    Sim, Biow Ing; Muhamad, Halimah; Lai, Oi Ming; Abas, Faridah; Yeoh, Chee Beng; Nehdi, Imededdine Arbi; Khor, Yih Phing; Tan, Chin Ping

    2018-04-01

    This paper examines the interactions of degumming and bleaching processes as well as their influences on the formation of 3-monochloropropane-1,2-diol esters (3-MCPDE) and glycidyl esters in refined, bleached and deodorized palm oil by using D-optimal design. Water degumming effectively reduced the 3-MCPDE content up to 50%. Acid activated bleaching earth had a greater effect on 3-MCPDE reduction compared to natural bleaching earth and acid activated bleaching earth with neutral pH, indicating that performance and adsorption capacities of bleaching earth are the predominant factors in the removal of esters, rather than its acidity profile. The combination of high dosage phosphoric acid during degumming with the use of acid activated bleaching earth eliminated almost all glycidyl esters during refining. Besides, the effects of crude palm oil quality was assessed and it was found that the quality of crude palm oil determines the level of formation of 3-MCPDE and glycidyl esters in palm oil during the high temperature deodorization step of physical refining process. Poor quality crude palm oil has strong impact towards 3-MCPDE and glycidyl esters formation due to the intrinsic components present within. The findings are useful to palm oil refining industry in choosing raw materials as an input during the refining process.

  7. Television advertisement format and the provision of risk information about prescription drug products.

    Science.gov (United States)

    Glinert, Lewis H; Schommer, Jon C

    2005-06-01

    Considerable attention has been afforded to analyzing the content of and assessing consumers' reaction to print direct-to-consumer drug ads, but not so for televised ads. To determine whether advertisements with different risk severity and risk presentation would significantly affect viewers' (1) recall of information contained in the advertisement, (2) evaluation of the advertisement, and (3) perceptions of the advertised product's risks. Data were collected from a sample of 135 first-year pharmacy students at a Midwestern college of pharmacy. After viewing 1 of the 6 advertisements designed for this study, participants were asked to complete a self-administered survey. Chi-square and analysis of variance were used to analyze the data. A 2x3 between subjects design was used to test the effects of 2 levels of risk severity (high- vs low-risk severity) and 3 levels of risk presentation (original ad containing integrated risk message, deintegrated risk message/dual modality using male voice-over, deintegrated risk message/dual modality using female voice-over). Results of analysis of variance procedures revealed that deintegrating risk information by placing it at the end of the advertisement and the use of captions in addition to oral messages (dual modality) (1) improved the recall of general and specific side effect information, (2) led to a perception that the advertisement had greater informational content, (3) resulted in lower Advertisement Distraction, and (4) lessened cognitive and affective aspects of information overload for the advertisement containing the high-risk severity medication. However, this pattern of findings was not found for the low-risk severity medication. Alternative methods for presenting risk information in direct-to-consumer ads affected some aspects of information recall and advertisement evaluation, but were not shown to affect risk perceptions regarding the advertised products.

  8. Environmental contamination, product contamination and workers exposure using a robotic system for antineoplastic drug preparation.

    Science.gov (United States)

    Sessink, Paul J M; Leclercq, Gisèle M; Wouters, Dominique-Marie; Halbardier, Loïc; Hammad, Chaïma; Kassoul, Nassima

    2015-04-01

    Environmental contamination, product contamination and technicians exposure were measured following preparation of iv bags with cyclophosphamide using the robotic system CytoCare. Wipe samples were taken inside CytoCare, in the clean room environment, from vials, and prepared iv bags including ports and analysed for contamination with cyclophosphamide. Contamination with cyclophosphamide was also measured in environmental air and on the technicians hands and gloves used for handling the drugs. Exposure of the technicians to cyclophosphamide was measured by analysis of cyclophosphamide in urine. Contamination with cyclophosphamide was mainly observed inside CytoCare, before preparation, after preparation and after daily routine cleaning. Contamination outside CytoCare was incidentally found. All vials with reconstituted cyclophosphamide entering CytoCare were contaminated on the outside but vials with powdered cyclophosphamide were not contaminated on the outside. Contaminated bags entering CytoCare were also contaminated after preparation but non-contaminated bags were not contaminated after preparation. Cyclophosphamide was detected on the ports of all prepared bags. Almost all outer pairs of gloves used for preparation and daily routine cleaning were contaminated with cyclophosphamide. Cyclophosphamide was not found on the inner pairs of gloves and on the hands of the technicians. Cyclophosphamide was not detected in the stationary and personal air samples and in the urine samples of the technicians. CytoCare enables the preparation of cyclophosphamide with low levels of environmental contamination and product contamination and no measurable exposure of the technicians. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  9. 21 CFR 201.66 - Format and content requirements for over-the-counter (OTC) drug product labeling.

    Science.gov (United States)

    2010-04-01

    ... throat warning:” (G) Warning for drug products containing sodium phosphates set forth in § 201.307(b)(2... (excluding pregnancy) and all warnings for persons experiencing certain symptoms. The warnings under this... paragraphs (c)(5)(i) through (c)(5)(vii), (c)(5)(ix), and (c)(5)(x) of this section. (ix) The pregnancy...

  10. The War on Illegal Drug Production and Trafficking: An Economic Evaluation of Plan Colombia

    OpenAIRE

    Daniel Mejía; Pascual Restrepo

    2008-01-01

    This paper provides a thorough economic evaluation of the anti-drug policies implemented in Colombia between 2000 and 2006 under the so-called Plan Colombia. The paper develops a game theory model of the war against illegal drugs in producer countries. We explicitly model illegal drug markets, which allows us to account for the feedback effects between policies and market outcomes that are potentially important when evaluating large scale policy interventions such as Plan Colombia. We use ava...

  11. In silico drug metabolism and pharmacokinetic profiles of natural products from medicinal plants in the Congo basin.

    Science.gov (United States)

    Ntie-Kang, Fidele; Lifongo, Lydia L; Mbah, James A; Owono Owono, Luc C; Megnassan, Eugene; Mbaze, Luc Meva'a; Judson, Philip N; Sippl, Wolfgang; Efange, Simon M N

    2013-01-01

    Drug metabolism and pharmacokinetics (DMPK) assessment has come to occupy a place of interest during the early stages of drug discovery today. The use of computer modelling to predict the DMPK and toxicity properties of a natural product library derived from medicinal plants from Central Africa (named ConMedNP). Material from some of the plant sources are currently employed in African Traditional Medicine. Computer-based methods are slowly gaining ground in this area and are often used as preliminary criteria for the elimination of compounds likely to present uninteresting pharmacokinetic profiles and unacceptable levels of toxicity from the list of potential drug candidates, hence cutting down the cost of discovery of a drug. In the present study, we present an in silico assessment of the DMPK and toxicity profile of a natural product library containing ~3,200 compounds, derived from 379 species of medicinal plants from 10 countries in the Congo Basin forests and savannas, which have been published in the literature. In this analysis, we have used 46 computed physico-chemical properties or molecular descriptors to predict the absorption, distribution, metabolism and elimination and toxicity (ADMET) of the compounds. This survey demonstrated that about 45% of the compounds within the ConMedNP compound library are compliant, having properties which fall within the range of ADME properties of 95% of currently known drugs, while about 69% of the compounds have ≤ 2 violations. Moreover, about 73% of the compounds within the corresponding "drug-like" subset showed compliance. In addition to the verified levels of "drug-likeness", diversity and the wide range of measured biological activities, the compounds from medicinal plants in Central Africa show interesting DMPK profiles and hence could represent an important starting point for hit/lead discovery.

  12. Medicaid Drug Rebate Program Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — Product Data for Drugs in the Medicaid Drug Rebate Program. The rebate drug product data file contains the active drugs that have been reported by participating drug...

  13. 78 FR 12760 - Guidance for Industry on Labeling for Human Prescription Drug and Biological Products...

    Science.gov (United States)

    2013-02-25

    ...--Implementing the Physician Labeling Rule Content and Format Requirements; Availability AGENCY: Food and Drug...--Implementing the PLR Content and Format Requirements.'' This guidance is intended to assist applicants in complying with the content and format requirements of labeling for human prescription drug and biological...

  14. 75 FR 67054 - Listing of Approved Drug Products Containing Dronabinol in Schedule III

    Science.gov (United States)

    2010-11-01

    ... sponsor may manufacture and market the generic drug to provide a safe, effective, and low cost alternative... record and made available for public inspection online at http://www.regulations.gov and in the Drug... posted online or made available in the public docket, you must include the phrase ``PERSONAL IDENTIFYING...

  15. 77 FR 47397 - Request for Nominations of Specific Drug/Biologic Product(s) That Could Be Brought Before the...

    Science.gov (United States)

    2012-08-08

    ... decision-making processes. Significant public health and safety issues are brought before these committees... future pediatric product development by focusing on products whose development would benefit the most...

  16. Limited Bacterial Diversity within a Treatment Plant Receiving Antibiotic-Containing Waste from Bulk Drug Production

    Science.gov (United States)

    Shouche, Yogesh S.; Larsson, D. G. Joakim

    2016-01-01

    Biological treatment of waste water from bulk drug production, contaminated with high levels of fluoroquinolone antibiotics, can lead to massive enrichment of antibiotic resistant bacteria, resistance genes and associated mobile elements, as previously shown. Such strong selection may be boosted by the use of activated sludge (AS) technology, where microbes that are able to thrive on the chemicals within the wastewater are reintroduced at an earlier stage of the process to further enhance degradation of incoming chemicals. The microbial community structure within such a treatment plant is, however, largely unclear. In this study, Illumina-based 16S rRNA amplicon sequencing was applied to investigate the bacterial communities of different stages from an Indian treatment plant operated by Patancheru Environment Technology Limited (PETL) in Hyderabad, India. The plant receives waste water with high levels of fluoroquinolones and applies AS technology. A total of 1,019,400 sequences from samples of different stages of the treatment process were analyzed. In total 202, 303, 732, 652, 947 and 864 operational taxonomic units (OTUs) were obtained at 3% distance cutoff in the equilibrator, aeration tanks 1 and 2, settling tank, secondary sludge and old sludge samples from PETL, respectively. Proteobacteria was the most dominant phyla in all samples with Gammaproteobacteria and Betaproteobacteria being the dominant classes. Alcaligenaceae and Pseudomonadaceae, bacterial families from PETL previously reported to be highly multidrug resistant, were the dominant families in aeration tank samples. Despite regular addition of human sewage (approximately 20%) to uphold microbial activity, the bacterial diversity within aeration tanks from PETL was considerably lower than corresponding samples from seven, regular municipal waste water treatment plants. The strong selection pressure from antibiotics present may be one important factor in structuring the microbial community in PETL

  17. Limited Bacterial Diversity within a Treatment Plant Receiving Antibiotic-Containing Waste from Bulk Drug Production.

    Science.gov (United States)

    Marathe, Nachiket P; Shetty, Sudarshan A; Shouche, Yogesh S; Larsson, D G Joakim

    2016-01-01

    Biological treatment of waste water from bulk drug production, contaminated with high levels of fluoroquinolone antibiotics, can lead to massive enrichment of antibiotic resistant bacteria, resistance genes and associated mobile elements, as previously shown. Such strong selection may be boosted by the use of activated sludge (AS) technology, where microbes that are able to thrive on the chemicals within the wastewater are reintroduced at an earlier stage of the process to further enhance degradation of incoming chemicals. The microbial community structure within such a treatment plant is, however, largely unclear. In this study, Illumina-based 16S rRNA amplicon sequencing was applied to investigate the bacterial communities of different stages from an Indian treatment plant operated by Patancheru Environment Technology Limited (PETL) in Hyderabad, India. The plant receives waste water with high levels of fluoroquinolones and applies AS technology. A total of 1,019,400 sequences from samples of different stages of the treatment process were analyzed. In total 202, 303, 732, 652, 947 and 864 operational taxonomic units (OTUs) were obtained at 3% distance cutoff in the equilibrator, aeration tanks 1 and 2, settling tank, secondary sludge and old sludge samples from PETL, respectively. Proteobacteria was the most dominant phyla in all samples with Gammaproteobacteria and Betaproteobacteria being the dominant classes. Alcaligenaceae and Pseudomonadaceae, bacterial families from PETL previously reported to be highly multidrug resistant, were the dominant families in aeration tank samples. Despite regular addition of human sewage (approximately 20%) to uphold microbial activity, the bacterial diversity within aeration tanks from PETL was considerably lower than corresponding samples from seven, regular municipal waste water treatment plants. The strong selection pressure from antibiotics present may be one important factor in structuring the microbial community in PETL

  18. Limited Bacterial Diversity within a Treatment Plant Receiving Antibiotic-Containing Waste from Bulk Drug Production.

    Directory of Open Access Journals (Sweden)

    Nachiket P Marathe

    Full Text Available Biological treatment of waste water from bulk drug production, contaminated with high levels of fluoroquinolone antibiotics, can lead to massive enrichment of antibiotic resistant bacteria, resistance genes and associated mobile elements, as previously shown. Such strong selection may be boosted by the use of activated sludge (AS technology, where microbes that are able to thrive on the chemicals within the wastewater are reintroduced at an earlier stage of the process to further enhance degradation of incoming chemicals. The microbial community structure within such a treatment plant is, however, largely unclear. In this study, Illumina-based 16S rRNA amplicon sequencing was applied to investigate the bacterial communities of different stages from an Indian treatment plant operated by Patancheru Environment Technology Limited (PETL in Hyderabad, India. The plant receives waste water with high levels of fluoroquinolones and applies AS technology. A total of 1,019,400 sequences from samples of different stages of the treatment process were analyzed. In total 202, 303, 732, 652, 947 and 864 operational taxonomic units (OTUs were obtained at 3% distance cutoff in the equilibrator, aeration tanks 1 and 2, settling tank, secondary sludge and old sludge samples from PETL, respectively. Proteobacteria was the most dominant phyla in all samples with Gammaproteobacteria and Betaproteobacteria being the dominant classes. Alcaligenaceae and Pseudomonadaceae, bacterial families from PETL previously reported to be highly multidrug resistant, were the dominant families in aeration tank samples. Despite regular addition of human sewage (approximately 20% to uphold microbial activity, the bacterial diversity within aeration tanks from PETL was considerably lower than corresponding samples from seven, regular municipal waste water treatment plants. The strong selection pressure from antibiotics present may be one important factor in structuring the microbial

  19. Dandruff, seborrheic dermatitis, and psoriasis drug products containing coal tar and menthol for over-the-counter human use; amendment to the monograph. Final rule

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-03-15

    The Food and Drug Administration (FDA) is issuing a final rule amending the final monograph (FM) for over-the-counter (OTC) dandruff, seborrheic dermatitis, and psoriasis drug products to include the combination of 1.8 percent coal tar solution and 1.5 percent menthol in a shampoo drug product to control dandruff. FDA did not receive any comments or data in response to its previously proposed rule to include this combination. This final rule is part of FDA's ongoing review of OTC drug products.

  20. 78 FR 68854 - Over-the-Counter Ophthalmic Drug Products-Emergency Use Eyewash Products; Rescheduling of Public...

    Science.gov (United States)

    2013-11-15

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-1038... information on the formulation, manufacturing, and labeling of currently marketed over- the-counter (OTC... hearing will be held on March 7, 2014, from 9 a.m. to 5 p.m. Submit electronic or written requests to make...

  1. Assessing the drug-likeness of lamellarins, a marine-derived natural product class with diverse oncological activities.

    Science.gov (United States)

    Chittchang, Montakarn; Gleeson, M Paul; Ploypradith, Poonsakdi; Ruchirawat, Somsak

    2010-06-01

    Natural products currently represent an underutilized source of leads for the pharmaceutical industry, especially when one considers that almost 50% of all drugs were either derived from such sources or are very closely related. Lamellarins are a class of natural products with diverse biological activities and have entered into preclinical development for the treatment of multidrug-resistant tumors. Although these compounds demonstrated good cell penetration, as observed by their low microM activity in whole cell models, they have not been extensively profiled from a physicochemical point of view, and this is the goal of this study. For this study, we have determined the experimental logP values of a set of 25 lamellarins, given it is the single most important parameter in determining multiple ADMET parameters. We also discuss the relationship between this natural product class, natural product derivatives in development and on the market, oral marketed drugs, as well as drug molecules in development, using a range of physicochemical parameters in conjunction with principal components analysis (PCA). The impact of this systematic analysis on our ongoing medicinal chemistry strategy is also discussed. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

  2. Antiretroviral solid drug nanoparticles with enhanced oral bioavailability: production, characterization, and in vitro-in vivo correlation.

    Science.gov (United States)

    McDonald, Tom O; Giardiello, Marco; Martin, Philip; Siccardi, Marco; Liptrott, Neill J; Smith, Darren; Roberts, Phill; Curley, Paul; Schipani, Alessandro; Khoo, Saye H; Long, James; Foster, Alison J; Rannard, Steven P; Owen, Andrew

    2014-03-01

    Nanomedicine strategies have produced many commercial products. However, no orally dosed HIV nanomedicines are available clinically to patients. Although nanosuspensions of drug particles have demonstrated many benefits, experimentally achieving >25 wt% of drug relative to stabilizers is highly challenging. In this study, the emulsion-templated freeze-drying technique for nanoparticles formation is applied for the first time to optimize a nanodispersion of the leading non-nucleoside reverse transcriptase inhibitor efavirenz, using clinically acceptable polymers and surfactants. Dry monoliths containing solid drug nanoparticles with extremely high drug loading (70 wt% relative to polymer and surfactant stabilizers) are stable for several months and reconstitute in aqueous media to provide nanodispersions with z-average diameters of 300 nm. The solid drug nanoparticles exhibit reduced cytoxicity and increased in vitro transport through model gut epithelium. In vivo studies confirm bioavailability benefits with an approximately four-fold higher pharmacokinetic exposure after oral administration to rodents, and predictive modeling suggests dose reduction with the new formulation may be possible. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Discrepancies in listed adverse drug reactions in pharmaceutical product information supplied by the regulatory authorities in Denmark and the USA.

    Science.gov (United States)

    Eriksson, Robert; Aagaard, Lise; Jensen, Lars Juhl; Borisova, Liza; Hørlück, Dorte; Brunak, Søren; Hansen, Ebba Holme

    2014-06-01

    Pharmaceutical product information (PI) supplied by the regulatory authorities serves as a source of information on safe and effective use of drugs. The objectives of this study were to qualitatively and quantitatively compare PIs for selected drugs marketed in both Denmark and the USA with respect to consistency and discrepancy of listed adverse drug reaction (ADR) information. We compared individual ADRs listed in PIs from Denmark and the USA with respect to type and frequency. Consistency was defined as match of ADRs and of ADR frequency or match could not be ruled out. Discrepancies were defined as ADRs listed only in one country or listed with different frequencies. We analyzed PIs for 40 separate drugs from ten therapeutic groups and assigned the 4003 identified ADRs to System Organ Classes (Medical Dictionary for Regulatory Activities [MedDRA] terminology). Less than half of listed ADRs (n = 1874; 47%) showed consistency. Discrepancies (n = 2129; 53%) were split into ADRs listed only in the USA (n = 1558; 39%), ADRs listed only in Denmark (n = 325; 8%) and ADRs listed with different frequencies (n = 246; 6%). The majority of listed ADRs were of the type "gastrointestinal disorders" and "nervous system disorders". Our results show great differences in PIs for drugs approved in both Denmark and the USA illuminating concerns about the credibility of the publicly available PIs. The results also represent an argument for further harmonization across borders to improve consistency between authority-supplied information.

  4. Accuracy of drug advertisements in medical journals under new law regulating the marketing of pharmaceutical products in Switzerland.

    Science.gov (United States)

    Santiago, Macarena Gonzalez; Bucher, Heiner C; Nordmann, Alain J

    2008-12-31

    New legal regulations for the marketing of pharmaceutical products were introduced in 2002 in Switzerland. We investigated whether claims in drug advertisements citing published scientific studies were justified by these studies after the introduction of these new regulations. In this cross-sectional study, two independent reviewers screened all issues of six major Swiss medical journals published in the year 2005 to identify all drug advertisements for analgesic, gastrointestinal and psychopharmacologic drugs and evaluated all drug advertisements referring to at least one publication. The pharmaceutical claim was rated as being supported, being based on a potentially biased study or not to be supported by the cited study according to pre-specified criteria. We also explored factors likely to be associated with supported advertisement claims. Of 2068 advertisements 577 (28%) promoted analgesic, psychopharmacologic or gastrointestinal drugs. Among them were 323 (56%) advertisements citing at least one reference. After excluding multiple publications of the same drug advertisement and advertisements with non-informative references, there remained 29 unique advertisements with at least one reference to a scientific study. These 29 advertisements contained 78 distinct pairs of claims of analgesic, gastrointestinal and psychopharmacologic drugs and referenced studies. Thirty-seven (47%) claims were supported, 16 (21%) claims were not supported by the corresponding reference, and 25 (32%) claims were based on potentially biased evidence, with no relevant differences between drug groups. Studies with conflict of interest and studies stating industry funding were more likely to support the corresponding claim (RR 1.52, 95% CI 1.07-2.17 and RR 1.50, 95% CI 0.98-2.28) than studies without identified conflict of interest and studies without information on type of funding. Following the introduction of new regulations for drug advertisement in Switzerland, 53% of all assessed

  5. PENGARUH PEMBERIAN MANURE AYAM PETELUR TERFERMENTASI DALAM PAKAN YANG DITAMBAH ORGANIC DEODORANT TERHADAP PERFORMA ITIK JANTAN UMUR 7-12 MINGGU

    Directory of Open Access Journals (Sweden)

    Djuriono (Djuriono

    2015-02-01

    Full Text Available The research was conducted to analyze the effect of organic deodorant supplemented fermented laying hens manure feeding on the performance of 7-12 weeks male ducks. One hundred 7 weeks old male ducks were used to study the effetct MODF supplementation on performance of male ducks. The ducks were divided into five groups with four replications consisting of five birds each. The treatment were PO = commercial feed without MODF supplementation (control, P15= commercial feed + 15% MODF, P30= commercial feed + 30% MODF, P45= commercial feed + 45% MODF, P60= commercial feed + 60% MODF. Data were analyzed with One-Way Classification of Completely Randomized Design and followed by Duncan’s New Multiple Range Test (DMRT for significant results. Results showed that supplementation of fermented MOD gave negative effect (P<0.05 on male ducks performance. The highest consumption was in P0 (5203.50 g, followed by P45% (5130.00 g, P30% (5002.75 g, P15% (4967.75 g, P0% (4856.75 g. The highest weight gain showed in P0 (649.80 g, followed by P15 (622.10 g, P30 (579.45 g, P45 (497.50 g, P60 (409.60 g. The higest feed convertion was in P60 (12.71, followed by P45 (10.31, P30 (8.64, P15 (7.99, P0 (7.48. It could be concluded that it is useless to supplement commercial diet of with MODF even though supplementation of 30% income over feed cost (IOFC showed better IOFC of 7-12 weeks male ducks. (Key words: Fermentated organic deodorant, Laying hens manure, Males ducks, Performance

  6. Scientific Perspectives on Extending the Provision for Waivers of In vivo Bioavailability and Bioequivalence Studies for Drug Products Containing High Solubility-Low Permeability Drugs (BCS-Class 3)

    OpenAIRE

    Stavchansky, Salomon

    2008-01-01

    Recently, there has been increased interest in extending the provision for waivers of in vivo bioavailability and bioequivalence (BA–BE) studies that appeared in the guidance published by the Food and Drug Administration (FDA) (1) to pharmaceutical products containing Class 3 drugs (High solubility–Low Permeability). The extension of the Biopharmaceutics Classification System (BCS) to Class 3 drugs is meritorious because of its impact on public health policy considerations. The rate limiting ...

  7. The Application of the Accelerated Stability Assessment Program (ASAP) to Quality by Design (QbD) for Drug Product Stability

    OpenAIRE

    Waterman, Kenneth Craig

    2011-01-01

    An isoconversion paradigm, where times in different temperature and humidity-controlled stability chambers are set to provide a fixed degradant level, is shown to compensate for the complex, non-single order kinetics of solid drug products. A humidity-corrected Arrhenius equation provides reliable estimates for temperature and relative humidity effects on degradation rates. A statistical protocol is employed to determine best fits for chemical stability data, which in turn allows for accurate...

  8. An analysis of psychotropic drug sales. Increasing sales of selective serotonin reuptake inhibitors are closely related to number of products.

    Science.gov (United States)

    Nielsen, Margrethe; Gøtzsche, Peter

    2011-01-01

    Prescribing of selective serotonin reuptake inhibitors (SSRIs) has increased dramatically. To compare the sales of benzodiazepines and SSRIs within the primary care sector in Denmark and relate changes in usage to number of indications and products on the market. We used data from various sources to establish the sales curves of psychotropic drugs in the period 1970 to 2007, based on the Anatomic Therapeutic Classification system and Defined Daily Doses. Fluctuations in sales of psychotropic drugs that cannot be explained by disease prevalence were caused by changes in sales of the benzodiazepines and SSRIs. We found a decline in the sales of benzodiazepines after a peak in 1986, likely due to the recognition that they cause dependence. From a low level in 1992, we found that the sales of SSRIs increased almost linearly by a factor of 18, up to 44 DDD per 1000 inhabitants, which was closely related to the number of products on the market that increased by a factor of 16. Sales of antidepressant drugs are mainly determined by market availability of products indicating that marketing pressures are playing an important role. Thus the current level of use of SSRIs may not be evidence-based, which is supported by studies showing that the effect of SSRIs has been overestimated.

  9. A brave new beef: The US Food and Drug Administration's review of the safety of cloned animal products.

    Science.gov (United States)

    Solomon, Louis M; Noll, Rebekka C; Mordkoff, David S; Murphy, Patrick; Rolerson, Marcy

    2009-09-01

    To meet its public mandate, the US Food and Drug Administration (FDA) collected studies on the potential health hazards of eating or drinking cloned food products. Based on an earlier National Academy of Sciences study that, on closer analysis, was not nearly as sanguine, the FDA's report found no evidence of a health risk from the public's ingestion of cloned food products. This article analyzes the risks the FDA considered, and concludes that there is a disconnect between the risks the FDA assessed in these studies and the risks that might arise from cloned food products. The FDA should consider instituting effective tracking mechanisms and other diagnostics that would permit scientists and the public to answer the question of health risks posed by cloned food products.

  10. Biopharming, bananas and bureaucracy: the banana vaccine as a case study for products that straddle the definitional food/drug divide.

    Science.gov (United States)

    Birdsall, Margaux

    2011-01-01

    This paper examines the definition of the terms "food" and "drug" as used in the Food, Drug and Cosmetic Act through the lens of biopharmed products. The paper uses the so-called "banana vaccine" as a case study to highlight the problems that occur when attempting to regulate a product that could be safely used as a food or as a drug. Specifically, the examination of this model illustrates the problems in the current definitional scheme. The paper considers how a product that straddles the definitional line between food and drug could be regulated and proposes a reformation to how the definitions are applied to products to better suit new technology in food and drugs.

  11. Mixing monoclonal antibody formulations using bottom-mounted mixers: impact of mechanism and design on drug product quality.

    Science.gov (United States)

    Gikanga, Benson; Chen, Yufei; Stauch, Oliver B; Maa, Yuh-Fun

    2015-01-01

    Using bottom-mounted mixers, particularly those that are magnetically driven, is becoming increasingly common during the mixing process in pharmaceutical and biotechnology manufacturing because of their associated low risk of contamination, ease of use, and ability to accommodate low minimum mixing volumes. Despite these benefits, the impact of bottom-mounted mixers on biologic drug product is not yet fully understood and is scarcely reported. This study evaluated four bottom-mounted mixers to assess their impact on monoclonal antibody formulations. Changes in product quality (size variants, particles, and turbidity) and impact on process performance (sterile filtration) were evaluated after mixing. The results suggested that mixers that are designed to function with no contact between the impeller and the drive unit are the most favorable and gentle to monoclonal antibody molecules. Designs with contact or a narrow clearance tended to shear and grind the protein and resulted in high particle count in the liquid, which would subsequently foul a filter membrane during sterile filtration using a 0.22 μm pore size filter. Despite particle formation, increases in turbidity of the protein solution and protein aggregation/fragmentation were not detected. Further particle analysis indicated particles in the range of 0.2-2 μm are responsible for filter fouling. A small-scale screening model was developed using two types of magnetic stir bars mimicking the presence or absence of contact between the impeller and drive unit in the bottom-mounted mixers. The model is capable of differentiating the sensitivity of monoclonal antibody formulations to bottom-mounted mixers with a small sample size. This study fills an important gap in understanding a critical bioprocess unit operation. Mixing is an important unit operation in drug product manufacturing for compounding (dilution, pooling, homogenization, etc.). The current trend in adopting disposable bottom-mounted mixers has

  12. Simulated Leaching (Migration) Study for a Model Container-Closure System Applicable to Parenteral and Ophthalmic Drug Products.

    Science.gov (United States)

    Jenke, Dennis; Egert, Thomas; Hendricker, Alan; Castner, James; Feinberg, Tom; Houston, Christopher; Hunt, Desmond G; Lynch, Michael; Nicholas, Kumudini; Norwood, Daniel L; Paskiet, Diane; Ruberto, Michael; Smith, Edward J; Holcomb, Frank; Markovic, Ingrid

    2017-01-01

    A simulating leaching (migration) study was performed on a model container-closure system relevant to parenteral and ophthalmic drug products. This container-closure system consisted of a linear low-density polyethylene bottle (primary container), a polypropylene cap and an elastomeric cap liner (closure), an adhesive label (labeling), and a foil overpouch (secondary container). The bottles were filled with simulating solvents (aqueous salt/acid mixture at pH 2.5, aqueous buffer at pH 9.5, and 1/1 v/v isopropanol/water), a label was affixed to the filled and capped bottles, the filled bottles were placed into the foil overpouch, and the filled and pouched units were stored either upright or inverted for up to 6 months at 40 °C. After storage, the leaching solutions were tested for leached substances using multiple complementary analytical techniques to address volatile, semi-volatile, and non-volatile organic and inorganic extractables as potential leachables.The leaching data generated supported several conclusions, including that (1) the extractables (leachables) profile revealed by a simulating leaching study can qualitatively be correlated with compositional information for materials of construction, (2) the chemical nature of both the extracting medium and the individual extractables (leachables) can markedly affect the resulting profile, and (3) while direct contact between a drug product and a system's material of construction may exacerbate the leaching of substances from that material by the drug product, direct contact is not a prerequisite for migration and leaching to occur. LAY ABSTRACT: The migration of container-related extractables from a model pharmaceutical container-closure system and into simulated drug product solutions was studied, focusing on circumstances relevant to parenteral and ophthalmic drug products. The model system was constructed specifically to address the migration of extractables from labels applied to the outside of the

  13. Influence of Different Container Closure Systems and Capping Process Parameters on Product Quality and Container Closure Integrity (CCI) in GMP Drug Product Manufacturing.

    Science.gov (United States)

    Mathaes, Roman; Mahler, Hanns-Christian; Roggo, Yves; Huwyler, Joerg; Eder, Juergen; Fritsch, Kamila; Posset, Tobias; Mohl, Silke; Streubel, Alexander

    2016-01-01

    Capping equipment used in good manufacturing practice manufacturing features different designs and a variety of adjustable process parameters. The overall capping result is a complex interplay of the different capping process parameters and is insufficiently described in literature. It remains poorly studied how the different capping equipment designs and capping equipment process parameters (e.g., pre-compression force, capping plate height, turntable rotating speed) contribute to the final residual seal force of a sealed container closure system and its relation to container closure integrity and other drug product quality parameters. Stopper compression measured by computer tomography correlated to residual seal force measurements.In our studies, we used different container closure system configurations from different good manufacturing practice drug product fill & finish facilities to investigate the influence of differences in primary packaging, that is, vial size and rubber stopper design on the capping process and the capped drug product. In addition, we compared two large-scale good manufacturing practice manufacturing capping equipment and different capping equipment settings and their impact on product quality and integrity, as determined by residual seal force.The capping plate to plunger distance had a major influence on the obtained residual seal force values of a sealed vial, whereas the capping pre-compression force and the turntable rotation speed showed only a minor influence on the residual seal force of a sealed vial. Capping process parameters could not easily be transferred from capping equipment of different manufacturers. However, the residual seal force tester did provide a valuable tool to compare capping performance of different capping equipment. No vial showed any leakage greater than 10(-8)mbar L/s as measured by a helium mass spectrometry system, suggesting that container closure integrity was warranted in the residual seal force range

  14. [Applying dose banding to the production of antineoplastic drugs: a narrative review of the literature].

    Science.gov (United States)

    Pérez Huertas, Pablo; Cueto Sola, Margarita; Escobar Cava, Paloma; Borrell García, Carmela; Albert Marí, Asunción; López Briz, Eduardo; Poveda Andrés, José Luis

    2015-07-01

    The dosage of antineoplastic drugs has historically been based on individualized prescription and preparation according to body surface area or patient´s weight. Lack of resources and increased assistance workload in the areas where chemotherapy is made, are leading to the development of new systems to optimize the processing without reducing safety. One of the strategies that has been proposed is the elaboration by dose banding. This new approach standardizes the antineoplastic agents doses by making ranges or bands accepting a percentage of maximum variation. It aims to reduce processing time with the consequent reduction in waiting time for patients; to reduce errors in the manufacturing process and to promote the rational drug use. In conclusion, dose banding is a suitable method for optimizing the development of anticancer drugs, obtaining reductions in oncologic patients waiting time but without actually causing a favorable impact on direct or indirect costs. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  15. Applying dose banding to the production of antineoplastic drugs: a narrative review of the literature

    Directory of Open Access Journals (Sweden)

    Pablo Pérez Huertas

    2015-07-01

    Full Text Available The dosage of antineoplastic drugs has historically been based on individualized prescription and preparation according to body surface area or patient´s weight. Lack of resources and increased assistance workload in the areas where chemotherapy is made, are leading to the development of new systems to optimize the processing without reducing safety. One of the strategies that has been proposed is the elaboration by dose banding. This new approach standardizes the antineoplastic agents doses by making ranges or bands accepting a percentage of maximum variation. It aims to reduce processing time with the consequent reduction in waiting time for patients; to reduce errors in the manufacturing process and to promote the rational drug use. In conclusion, dose banding is a suitable method for optimizing the development of anticancer drugs, obtaining reductions in oncologic patients waiting time but without actually causing a favorable impact on direct or indirect costs.

  16. [Sleep disorders and impaired sleep as adverse drug reactions of psychotropic drugs: an evaluation of data of summaries of product characteristics].

    Science.gov (United States)

    Gahr, Maximilian; Connemann, Bernhard J; Zeiss, René; Fröhlich, Albrecht

    2018-03-02

     Psychopharmacotherapy is essential in the treatment of many mental disorders. Adverse drug reactions (ADR) have impact on compliance and tolerability. Sleep disorders or impaired sleep may occur as ADRs of psychopharmacotherapy. Sleep disorders are associated with an increased risk for physical and mental illness and may impair cognition, impulse control, emotion regulation and mood. Objective of the following study was the systematic presentation of type and risk of sleep disorders/impairments of sleep of frequently prescribed psychotropic drugs.  Psychotropic agents that are most frequently prescribed in Germany were identified by using the Arzneiverordnungs-Report 2016. Summaries of product characteristics (SmPC) of corresponding original products were analyzed regarding presence and frequency of sleep disorders/impairments of sleep according to the International Classification of Sleep Disorders 3 (ICSD-3).  N = 64 SmPCs were analyzed. In most of the analyzed SmPCs, at least one sleep disorder (50/64; 78 %) was listed. At least one SmPC with a corresponding ADR was found in the categories insomnia (52 %), parasomnias (33 %), and sleep-related movement disorders (20 %); sleep-related breathing disorders (6 %) and central disorders of hypersomnolence (5 %) were rarely listed; circadian rhythm sleep-wake disorder was not found. The SmPCs of the four most frequently prescribed agents (citalopram > venlafaxine > mirtazapine > sertraline) listed insomnia as an ADR. Nearly all analysed hypnotics (except chloral hydrate) were associated with nightmares.  Most of the psychotropic agents frequently prescribed in Germany may induce sleep disorders/impairments of sleep. The four most frequently prescribed agents were antidepressants and all of the corresponding SmPCs listed insomnia as a possible ADR. Sleep disorders should be taken seriously as possible ADRs of psychopharmacotherapy. © Georg Thieme Verlag KG Stuttgart · New York.

  17. 76 FR 66235 - Bar Code Technologies for Drugs and Biological Products; Retrospective Review Under Executive...

    Science.gov (United States)

    2011-10-26

    ... interactions, overdoses, and patient allergies) and retail pharmacy-based computer systems that use a bar-coded... drugs. The goal of this initiative is to implement a system to further ensure patient safety and to..., and ideas on the need, maturity, and acceptability of alternative identification technologies for the...

  18. Capillary electrokinetic separation techniques for profiling of drugs and related products

    NARCIS (Netherlands)

    Hilhorst, M.J; Somsen, G.W; de Jong, G.J.

    Capillary electrokinetic separation techniques offer high efficiency and peak capacity, and can be very useful for the analysis of samples containing a large variety of (unknown) compounds. Such samples are frequently met in impurity profiling of drugs (detection of potential impurities in a

  19. 77 FR 40069 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

    Science.gov (United States)

    2012-07-06

    ... being manufactured and distributed. In 2009, the Agency sent warning letters to companies manufacturing... opportunity to assess the adequacy of their chemistry, manufacturing, and controls specifications before...), have the potential to be highly addictive, and are extremely popular drugs of abuse. The particular...

  20. 78 FR 67985 - Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products

    Science.gov (United States)

    2013-11-13

    ... add or strengthen a statement about drug abuse, dependence, psychological effect, or overdosage; To... other aspect of labeling protected by patent or exclusivity. FDA has generally taken the position that a... patients with diabetes. Source: Published literature, epidemiologic study.'' iii. The basis for the...

  1. Application of Combination High-Throughput Phenotypic Screening and Target Identification Methods for the Discovery of Natural Product-Based Combination Drugs.

    Science.gov (United States)

    Isgut, Monica; Rao, Mukkavilli; Yang, Chunhua; Subrahmanyam, Vangala; Rida, Padmashree C G; Aneja, Ritu

    2018-03-01

    Modern drug discovery efforts have had mediocre success rates with increasing developmental costs, and this has encouraged pharmaceutical scientists to seek innovative approaches. Recently with the rise of the fields of systems biology and metabolomics, network pharmacology (NP) has begun to emerge as a new paradigm in drug discovery, with a focus on multiple targets and drug combinations for treating disease. Studies on the benefits of drug combinations lay the groundwork for a renewed focus on natural products in drug discovery. Natural products consist of a multitude of constituents that can act on a variety of targets in the body to induce pharmacodynamic responses that may together culminate in an additive or synergistic therapeutic effect. Although natural products cannot be patented, they can be used as starting points in the discovery of potent combination therapeutics. The optimal mix of bioactive ingredients in natural products can be determined via phenotypic screening. The targets and molecular mechanisms of action of these active ingredients can then be determined using chemical proteomics, and by implementing a reverse pharmacokinetics approach. This review article provides evidence supporting the potential benefits of natural product-based combination drugs, and summarizes drug discovery methods that can be applied to this class of drugs. © 2017 Wiley Periodicals, Inc.

  2. The production of volvox spheres and their potential application in multi-drugs encapsulation and release

    Energy Technology Data Exchange (ETDEWEB)

    Teong, Benjamin; Chang, Shwu Jen [Department of Biomedical Engineering, I-Shou University, College of Medicine, No. 8, Yida Rd., Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan (China); Chuang, Chin Wen [Department of Electrical Engineering, I-Shou University, No. 1, Sec. 1, Syuecheng Rd., Dashu District, Kaohsiung City 84001, Taiwan (China); Kuo, Shyh Ming, E-mail: smkuo@isu.edu.tw [Department of Biomedical Engineering, I-Shou University, College of Medicine, No. 8, Yida Rd., Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan (China); Manousakas, Ioannis, E-mail: i.manousakas@ieee.org [Department of Biomedical Engineering, I-Shou University, College of Medicine, No. 8, Yida Rd., Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan (China)

    2013-12-01

    Volvox sphere is a bio-mimicking concept of an innovative biomaterial structure of a sphere that contains smaller microspheres which then encapsulate chemicals, drugs and/or cells. The volvox spheres were produced via a high-voltage electrostatic field system, using alginate as the primary material. Encapsulated materials tested in this study include staining dyes, nuclear fast red and trypan blue, and model drugs, bovine serum albumin (BSA) and cytochrome c (CytC). The external morphology of the volvox spheres was observed via electron microscopy whereas the internal structure of the volvox spheres was observed via an optical microscope with the aid of the staining dyes, since alginate is colorless and transparent. The diameter of the microspheres was about 200 to 300 μm, whereas the diameter of the volvox spheres was about 1500 μm. Volvox spheres were durable, retaining about 95% of their mass after 4 weeks. Factors affecting entrapment efficiency, such as temperature and concentration of the bivalent cross-linker, were compared followed by a 7-day in vitro release study. The encapsulation efficiency of CytC within the microspheres was higher at cold (∼ 4 °C) and warm (∼ 50 °C) temperatures whereas temperature has no obvious effect on the BSA encapsulation. High crosslinking concentration (25% w/v) of calcium chloride has resulted higher entrapment efficiency for BSA but not for CytC. Furthermore, volvox spheres showed a different release pattern of BSA and CytC when compared to microspheres encapsulating BSA and CytC. Despite the fact that the mechanisms behind remain unclear and further investigation is required, this study demonstrates the potential of the volvox spheres for drug delivery. - Highlights: • Volvox spheres contain smaller microspheres which can encapsulate drugs and/or cells. • Alginate is the primary material for the inner and outer spheres. • Encapsulation is affected by the crosslinking, temperature and the selection of drugs.

  3. The production of volvox spheres and their potential application in multi-drugs encapsulation and release

    International Nuclear Information System (INIS)

    Teong, Benjamin; Chang, Shwu Jen; Chuang, Chin Wen; Kuo, Shyh Ming; Manousakas, Ioannis

    2013-01-01

    Volvox sphere is a bio-mimicking concept of an innovative biomaterial structure of a sphere that contains smaller microspheres which then encapsulate chemicals, drugs and/or cells. The volvox spheres were produced via a high-voltage electrostatic field system, using alginate as the primary material. Encapsulated materials tested in this study include staining dyes, nuclear fast red and trypan blue, and model drugs, bovine serum albumin (BSA) and cytochrome c (CytC). The external morphology of the volvox spheres was observed via electron microscopy whereas the internal structure of the volvox spheres was observed via an optical microscope with the aid of the staining dyes, since alginate is colorless and transparent. The diameter of the microspheres was about 200 to 300 μm, whereas the diameter of the volvox spheres was about 1500 μm. Volvox spheres were durable, retaining about 95% of their mass after 4 weeks. Factors affecting entrapment efficiency, such as temperature and concentration of the bivalent cross-linker, were compared followed by a 7-day in vitro release study. The encapsulation efficiency of CytC within the microspheres was higher at cold (∼ 4 °C) and warm (∼ 50 °C) temperatures whereas temperature has no obvious effect on the BSA encapsulation. High crosslinking concentration (25% w/v) of calcium chloride has resulted higher entrapment efficiency for BSA but not for CytC. Furthermore, volvox spheres showed a different release pattern of BSA and CytC when compared to microspheres encapsulating BSA and CytC. Despite the fact that the mechanisms behind remain unclear and further investigation is required, this study demonstrates the potential of the volvox spheres for drug delivery. - Highlights: • Volvox spheres contain smaller microspheres which can encapsulate drugs and/or cells. • Alginate is the primary material for the inner and outer spheres. • Encapsulation is affected by the crosslinking, temperature and the selection of drugs.

  4. The application of the Accelerated Stability Assessment Program (ASAP) to quality by design (QbD) for drug product stability.

    Science.gov (United States)

    Waterman, Kenneth Craig

    2011-09-01

    An isoconversion paradigm, where times in different temperature and humidity-controlled stability chambers are set to provide a fixed degradant level, is shown to compensate for the complex, non-single order kinetics of solid drug products. A humidity-corrected Arrhenius equation provides reliable estimates for temperature and relative humidity effects on degradation rates. A statistical protocol is employed to determine best fits for chemical stability data, which in turn allows for accurate estimations of shelf life (with appropriate confidence intervals) at any storage condition including inside packaging (based on the moisture vapor transmission rate of the packaging and moisture sorption isotherms of the internal components). These methodologies provide both faster results and far better predictions of chemical stability limited shelf life (expiry) than previously possible. Precise shelf-life estimations are generally determined using a 2-week, product-specific protocol. Once the model for a product is developed, it can play a critical role in providing the product understanding necessary for a quality by design (QbD) filing for product approval and enable rational control strategies to assure product stability. Moreover, this Accelerated Stability Assessment Program (ASAP) enables the coupling of product attributes (e.g., moisture content, packaging options) to allow for flexibility in how control strategies are implemented to provide a balance of cost, speed, and other factors while maintaining adequate stability.

  5. An analysis of FDA-approved drugs: natural products and their derivatives.

    Science.gov (United States)

    Patridge, Eric; Gareiss, Peter; Kinch, Michael S; Hoyer, Denton

    2016-02-01

    Natural products contribute greatly to the history and landscape of new molecular entities (NMEs). An assessment of all FDA-approved NMEs reveals that natural products and their derivatives represent over one-third of all NMEs. Nearly one-half of these are derived from mammals, one-quarter from microbes and one-quarter from plants. Since the 1930s, the total fraction of natural products has diminished, whereas semisynthetic and synthetic natural product derivatives have increased. Over time, this fraction has also become enriched with microbial natural products, which represent a significant portion of approved antibiotics, including more than two-thirds of all antibacterial NMEs. In recent years, the declining focus on natural products has impacted the pipeline of NMEs from specific classes, and this trend is likely to continue without specific investment in the pursuit of natural products. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Orally inhaled drug performance testing for product development, registration, and quality control.

    Science.gov (United States)

    Lastow, Orest; Svensson, Mårten

    2014-12-01

    A DPI can be split into three different modules; device, formulation, process. These are developed in parallel, and together with the user they provide the performance of an inhalation product. During product development, these modules are evolving and changing, whereas the requirements on an inhalation product are always expressed in terms of the performance of the final commercial product. To do performance testing during development when the product is not finished presents many challenges and can be confusing and misleading. During development, the performance of the final product is typically being predicted by testing ever changing prototypes. This article describes methods and approaches to manage such development and to, during development, provide relevant predictions of the in vitro and in vivo performances of the final product.

  7. [European Union regulatory and quality requirements for botanical drugs and their implications for Chinese herbal medicinal products development].

    Science.gov (United States)

    Zhu, You-Ping

    2017-06-01

    This paper introduces regulatory pathways and characteristic quality requirements for marketing authorization of herbal medicinal products in the European Union(EU), and the legal status and applications of "European Union list of herbal substances, preparations and combinations" and "European Union herbal monographs". Also introduced are Chinese herbs that have been granted the EU list entry, those with EU herbal monographs, and registered EU traditional herbal medicinal products with Chinese herbs as active ingredients. Special attention is paid to the technical details of three authorized EU herbal medicinal products (Veregen, Sativex and Episalvan) in comparison with Andrographis paniculata extract HMPL-004 that failed the phase Ⅲ clinical trial for ulcerative colitis. The paper further emphasizes the importance of enriching active fractions of herbal extracts and taking regulatory and quality considerations into account in early stage of botanical drug development. Copyright© by the Chinese Pharmaceutical Association.

  8. Post-consumer use efficacies of preservatives in personal care and topical drug products: relationship to preservative category.

    Science.gov (United States)

    Ravita, Timothy D; Tanner, Ralph S; Ahearn, Donald G; Arms, Erin L; Crockett, Patrick W

    2009-01-01

    Ninety-six used personal care and topical OTC drug items collected from consumers in the USA were examined for the presence of microbial contaminants. Of the eye and face product type containing global preservative chemistries (i.e., acceptable for use in Japan without major restrictions), 55% yielded numbers of microorganisms in excess of 500 CFU/g (P preservative chemistries, 79% yielded numbers of microorganisms in excess of 500 CFU/g (P preservative chemistries accounted for 88% (n = 14) of the products that had microbial contents above 10(4) CFU/g (P preserved with global preservative chemistries did not maintain as adequate preservation as products with non-global preservatives.

  9. Subvisible (2-100 μm) Particle Analysis During Biotherapeutic Drug Product Development: Part 1, Considerations and Strategy.

    Science.gov (United States)

    Narhi, Linda O; Corvari, Vincent; Ripple, Dean C; Afonina, Nataliya; Cecchini, Irene; Defelippis, Michael R; Garidel, Patrick; Herre, Andrea; Koulov, Atanas V; Lubiniecki, Tony; Mahler, Hanns-Christian; Mangiagalli, Paolo; Nesta, Douglas; Perez-Ramirez, Bernardo; Polozova, Alla; Rossi, Mara; Schmidt, Roland; Simler, Robert; Singh, Satish; Spitznagel, Thomas M; Weiskopf, Andrew; Wuchner, Klaus

    2015-06-01

    Measurement and characterization of subvisible particles (defined here as those ranging in size from 2 to 100 μm), including proteinaceous and nonproteinaceous particles, is an important part of every stage of protein therapeutic development. The tools used and the ways in which the information generated is applied depends on the particular product development stage, the amount of material, and the time available for the analysis. In order to compare results across laboratories and products, it is important to harmonize nomenclature, experimental protocols, data analysis, and interpretation. In this manuscript on perspectives on subvisible particles in protein therapeutic drug products, we focus on the tools available for detection, characterization, and quantification of these species and the strategy around their application. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. Ultrasonic characterization of vegetable oil product

    International Nuclear Information System (INIS)

    Sidek Hj Abd Aziz; Chow Sai Pew; Abdul Halim Shaari; Nor Azizah Shaari

    1992-01-01

    The ultrasonic wave velocity and attenuation of a number vegetable oil products were measured using an ultrasonic pulse echo overlap technique from room temperature up to 90 0 C. Among the liquid samples studied were refined bleach deodorized (RED) palm oil, palm olein, coconut oil, corn oil and soya bean oil. The velocity of sound in vegetable oil products varies from about 1200 to 200 ms-1 and decrease linearly as the temperature increases. The ultrasonic properties of the oil are much dependent on their viscosity, density, relaxation effect and vibrational anharmonicity

  11. 78 FR 57397 - Over-the-Counter Ophthalmic Drug Products-Emergency Use Eyewash Products; Announcement of Public...

    Science.gov (United States)

    2013-09-18

    ...-based solutions used in the workplace to flush or irrigate the eye to reduce the chance of severe injury... workplace EE stations. There are two general types of EE products: Large volume and small volume. FDA... hearing as described in this document conflict with any provisions set out in part 15, this notice acts as...

  12. Silicon microfluidic flow focusing devices for the production of size-controlled PLGA based drug loaded microparticles.

    Science.gov (United States)

    Keohane, Kieran; Brennan, Des; Galvin, Paul; Griffin, Brendan T

    2014-06-05

    The increasing realisation of the impact of size and surface properties on the bio-distribution of drug loaded colloidal particles has driven the application of micro fabrication technologies for the precise engineering of drug loaded microparticles. This paper demonstrates an alternative approach for producing size controlled drug loaded PLGA based microparticles using silicon Microfluidic Flow Focusing Devices (MFFDs). Based on the precise geometry and dimensions of the flow focusing channel, microparticle size was successfully optimised by modifying the polymer type, disperse phase (Qd) flow rate, and continuous phase (Qc) flow rate. The microparticles produced ranged in sizes from 5 to 50 μm and were highly monodisperse (coefficient of variation <5%). A comparison of Ciclosporin (CsA) loaded PLGA microparticles produced by MFFDs vs conventional production techniques was also performed. MFFDs produced microparticles with a narrower size distribution profile, relative to the conventional approaches. In-vitro release kinetics of CsA was found to be influenced by the production technique, with the MFFD approach demonstrating the slowest rate of release over 7 days (4.99 ± 0.26%). Finally, MFFDs were utilised to produce pegylated microparticles using the block co-polymer, PEG-PLGA. In contrast to the smooth microparticles produced using PLGA, PEG-PLGA microparticles displayed a highly porous surface morphology and rapid CsA release, with 85 ± 6.68% CsA released after 24h. The findings from this study demonstrate the utility of silicon MFFDs for the precise control of size and surface morphology of PLGA based microparticles with potential drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Clinical efficacy and health implications of inconsistency in different production batches of antimycotic drugs in a developing country.

    Science.gov (United States)

    Ogunshe, Adenike A O; Adepoju, Adedayo A; Oladimeji, Modupe E

    2011-01-01

    This study aimed at evaluating the in vitro efficacy and health implications of inconsistencies in different production batches of antimycotic drugs. in vitro susceptibility profiles of 36 Candida spp. - C. albicans (19.4%), C. glabrata (30.6%), C. tropicalis (33.3%), and C. pseudotropicalis (16.7%) - obtained from human endocervical and high vaginal swabs (ECS/HVS) to two different batches (B1 and B2) of six antimycotic drugs (clotrimazole, doxycycline, iconazole, itraconazole, metronidazole and nystatin) was determined using modified agar well-diffusion method. None of the Candida strains had entirely the same (100%) susceptibility / resistance profiles in both batches of corresponding antimycotic drugs; while, different multiple antifungal susceptibility (MAS) rates were also recorded in batches 1 and 2 for corresponding antifungals. Only 14.3%, 27.3%, 16.7-33.3%, and 8.3-25.0% of C. albicans, C. glabrata, C. pseudotropicalis, and C. tropicalis strains, respectively, had similar susceptibility/resistance profiles toward coressponding antifungal agents in both batches; while up to 57.1% of C. albicans, 45.5% of C. glabrata, 66.7% of C. pseudotropicalis, and 50.0% of C. tropicalis strains were susceptible to one batch of antifungals but resistant to corresponding antifungals in the second batch. As high as 71.4% (C. albicans), 73.0% (C. glabrata), 50.0% (C. pseudotropicalis), and 66.74% (C. tropicalis) strains had differences of ≥ 10.0 mm among corresponding antimycotic agents. Candida strains exhibited different in vitro susceptibility / resistance patterns toward two batches of corresponding antimycotic agents, which has clinical implications on the efficacy of the drugs and treatment of patients. The findings of the present study will be of benefit in providing additional information in support of submission of drugs for registration to appropriate regulatory agencies.

  14. The occurrence of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs in surface water in South Wales, UK.

    Science.gov (United States)

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M; Guwy, Alan J

    2008-07-01

    The presence and fate of 56 pharmaceuticals, personal care products, endocrine disruptors and illicit drugs (PPCPs) were investigated in the South Wales region of the UK. Two contrasting rivers: River Taff and River Ely were chosen for this investigation and were monitored for a period of 10 months. The impact of the factors affecting the levels of concentration of PPCPs and illicit drugs in surface water such as surrounding area, proximity to wastewater effluent and weather conditions, mainly rainfall was also investigated. Most PPCPs were frequently found in river water at concentrations reaching single microgL(-1) and their levels depended mainly on the extent of water dilution resulting from rainfall. Discharge of treated wastewater effluent into the river course was found to be the main cause of water contamination with PPCPs. The most frequently detected PPCPs represent the group of pharmaceuticals dispensed at the highest levels in the Welsh community. These were antibacterial drugs (trimethoprim, erythromycin-H(2)O and amoxicillin), anti-inflammatories/analgesics (paracetamol, tramadol, codeine, naproxen, ibuprofen and diclofenac) and antiepileptic drugs (carbamazepine and gabapentin). Only four PPCPs out of 56 (simvastatin, pravastatin, digoxin and digoxigenin) were not quantified over the course of the study. Several PPCPs were found to be both ubiquitous and persistent in the aqueous environment (e.g. erythromycin-H(2)O, codeine, carbamazepine, gabapentin and valsartan). The calculated average daily loads of PPCPs indicated that in total almost 6 kg of studied PPCPs are discharged daily into the studied rivers. The illicit drugs studied were found in rivers at low levels of ng L(-1). Average daily loads of amphetamine, cocaine and its main metabolite benzoylecgonine were as follows: 8, 1.2 and 39 gday(-1), respectively. Their frequent occurrence in surface water is primarily associated with their high illegal usage and is strongly associated with the

  15. Aldehyde-sequestering drugs: tools for studying protein damage by lipid peroxidation products.

    Science.gov (United States)

    Burcham, Philip C; Kaminskas, Lisa M; Fontaine, Frank R; Petersen, Dennis R; Pyke, Simon M

    2002-12-27

    Elevated levels of reactive alpha,beta-unsaturated aldehydes (e.g. malondialdehyde, 4-hydroxynonenal and acrolein) in the affected tissues of various degenerative conditions suggest these substances are active propagators of the disease process. One experimental approach to attenuating damage by these intermediates employs 'aldehyde-sequestering drugs' as sacrificial nucleophiles, thereby sparing cell macromolecules and perhaps slowing disease progression. Drugs with demonstrated trapping activity toward lipid-derived aldehydes include various amine compounds such as aminoguanidine, carnosine and pyridoxamine. We have focused on identifying scavengers of acrolein, perhaps the most toxic aldehyde formed during lipid peroxidation cascades. Various phthalazine compounds (hydralazine and dihydralazine) were found to trap acrolein readily, forming hydrazone derivatives in a rapid Schiff-type reaction. These compounds strongly protect against acrolein-mediated toxicity in isolated hepatocytes.

  16. A Thiopurine Drug Inhibits West Nile Virus Production in Cell Culture, but Not in Mice

    OpenAIRE

    Lim, Pei-Yin; Keating, Julie A.; Hoover, Spencer; Striker, Rob; Bernard, Kristen A.

    2011-01-01

    Many viruses within the Flavivirus genus cause significant disease in humans; however, effective antivirals against these viruses are not currently available. We have previously shown that a thiopurine drug, 6-methylmercaptopurine riboside (6MMPr), inhibits replication of distantly related viruses within the Flaviviridae family in cell culture, including bovine viral diarrhea virus and hepatitis C virus replicon. Here we further examined the potential antiviral effect of 6MMPr on several dive...

  17. Zolpidem prescribing practices before and after Food and Drug Administration required product labeling changes

    OpenAIRE

    Norman, Jessica L; Fixen, Danielle R; Saseen, Joseph J; Saba, Laura M; Linnebur, Sunny A

    2017-01-01

    Background: Women have higher morning serum zolpidem concentrations than men after taking an evening dose, potentially leading to increased risk of harm. On 19 April 2013, the United States Food and Drug Administration required labeling changes for zolpidem, recommending an initial dose of no greater than 5 mg (immediate release) or 6.25 mg (controlled release) per night in women. Objectives: The primary objective of this study was to compare prescribing practices before and after the 2013 zo...

  18. Global Scientific Production on Illicit Drug Addiction: A Two-Decade Analysis.

    Science.gov (United States)

    Khalili, Malahat; Rahimi-Movaghar, Afarin; Shadloo, Behrang; Mojtabai, Ramin; Mann, Karl; Amin-Esmaeili, Masoumeh

    2018-04-06

    Addiction science has made great progress in the past decades. We conducted a scientometric study in order to quantify the number of publications and the growth rate globally, regionally, and at country levels. In October 2015, we searched the Scopus database using the general keywords of addiction or drug-use disorders combined with specific terms regarding 4 groups of illicit drugs - cannabis, opioids, cocaine, and other stimulants or hallucinogens. All documents published during the 20-year period from 1995 to 2014 were included. A total of 95,398 documents were retrieved. The highest number of documents were on opioids, both globally (60.1%) and in each of 5 continents. However, studies on cannabis showed a higher growth rate in the last 5-year period of the study (2010-2014). The United States, the United Kingdom, Germany, Canada, Australia, France, Spain, Italy, China, and Japan - almost all studies were from high-income countries - occupied the top 10 positions and produced 81.4% of the global science on drug addiction. As there are important socio-cultural differences in the epidemiology and optimal clinical care of addictive disorders, it is suggested that low- and more affected middle-income countries increase their capacity to conduct research and disseminate the knowledge in this field. © 2018 S. Karger AG, Basel.

  19. The Longitudinal Effect of Drug Use on Productivity Status of Nonmetropolitan African American Young Adults

    Science.gov (United States)

    Roldós, María Isabel

    2014-01-01

    The purpose of this study was to investigate the longitudinal effect of marijuana and heavy alcohol use on the productivity status of nonmetropolitan African American young adults. This analysis was based on secondary data from the Family and Community Health Study. For alcohol, the study evaluated the effects on productivity status for…

  20. Stable production of the antimalarial drug artemisinin in the moss Physcomitrella patens

    DEFF Research Database (Denmark)

    Binti Khairul Ikram, Nur Kusaira; Kashkooli, Arman Beyraghdar; Peramuna, Anantha Vithakshana

    2017-01-01

    study shows that P. patens can be a sustainable and efficient production platform of artemisinin that without further modifications allow for industrial scale production. A stable supply of artemisinin will lower the price of artemisinin-based treatments, hence become more affordable to the lower income...

  1. Extractables characterization for five materials of construction representative of packaging systems used for parenteral and ophthalmic drug products.

    Science.gov (United States)

    Jenke, Dennis; Castner, James; Egert, Thomas; Feinberg, Tom; Hendricker, Alan; Houston, Christopher; Hunt, Desmond G; Lynch, Michael; Shaw, Arthur; Nicholas, Kumudini; Norwood, Daniel L; Paskiet, Diane; Ruberto, Michael; Smith, Edward J; Holcomb, Frank

    2013-01-01

    Polymeric and elastomeric materials are commonly encountered in medical devices and packaging systems used to manufacture, store, deliver, and/or administer drug products. Characterizing extractables from such materials is a necessary step in establishing their suitability for use in these applications. In this study, five individual materials representative of polymers and elastomers commonly used in packaging systems and devices were extracted under conditions and with solvents that are relevant to parenteral and ophthalmic drug products (PODPs). Extraction methods included elevated temperature sealed vessel extraction, sonication, refluxing, and Soxhlet extraction. Extraction solvents included a low-pH (pH = 2.5) salt mixture, a high-pH (pH = 9.5) phosphate buffer, a 1/1 isopropanol/water mixture, isopropanol, and hexane. The resulting extracts were chemically characterized via spectroscopic and chromatographic means to establish the metal/trace element and organic extractables profiles. Additionally, the test articles themselves were tested for volatile organic substances. The results of this testing established the extractables profiles of the test articles, which are reported herein. Trends in the extractables, and their estimated concentrations, as a function of the extraction and testing methodologies are considered in the context of the use of the test article in medical applications and with respect to establishing best demonstrated practices for extractables profiling of materials used in PODP-related packaging systems and devices. Plastic and rubber materials are commonly encountered in medical devices and packaging/delivery systems for drug products. Characterizing the extractables from these materials is an important part of determining that they are suitable for use. In this study, five materials representative of plastics and rubbers used in packaging and medical devices were extracted by several means, and the extracts were analytically

  2. Labeling and effectiveness testing; sunscreen drug products for over-the-counter human use; delay of compliance dates. Final rule; delay of compliance dates; request for comments.

    Science.gov (United States)

    2012-05-11

    The Food and Drug Administration (FDA) is delaying the compliance dates for the final rule for over-the-counter (OTC) sunscreen drug products that published in the Federal Register of June 17, 2011 (76 FR 35620). The final rule establishes labeling and effectiveness testing for certain OTC sunscreen products containing specified active ingredients and marketed without approved applications. It also amends labeling claims that are not currently supported by data and lifts the previously-published delay of implementation of the Drug Facts labeling requirements for OTC sunscreens. The 2011 final rule's compliance dates are being delayed because information received after publication of the 2011 final rule indicates that full implementation of the 2011 final rule's requirements for all affected products will require an additional 6 months. This final rule is part of FDA's ongoing review of OTC drug products.

  3. 21 CFR 310.534 - Drug products containing active ingredients offered over-the-counter (OTC) for human use as oral...

    Science.gov (United States)

    2010-04-01

    ... agents. Oral wound healing agents have been marketed as aids in the healing of minor oral wounds by means.... (c) Clinical investigations designed to obtain evidence that any drug product labeled, represented...

  4. Viability in the production of a drug extracted from Ananas comosus by a flat membrane system

    Directory of Open Access Journals (Sweden)

    Francisco Luiz Gumes Lopes

    2012-06-01

    Full Text Available The aim of this work was to study the production of e bromelain from the Ananas comosus L. Merril, by determining the process conditions using flat membranes. The production system modeling generated a hyperbolical curve and the optimization by response surfaces showed an influence of the transmembrane pressure higher than the pH influence. The cost of the production of bromelain from A. comosus was estimated 9 to 13 times lower than Sigma's retail sales price and 6.5 to 8.5 times lower than when this enzyme was obtained through a liquid-liquid extraction, which showed the economical feasibility of the process.

  5. Reforming the Regulation of Therapeutic Products in Canada: The Protecting of Canadians from Unsafe Drugs Act (Vanessa’s Law

    Directory of Open Access Journals (Sweden)

    Katherine Fierlbeck

    2016-11-01

    Full Text Available Enacted November 2014, Vanessa’s Law amends the Food and Drugs Act to give Health Canada greater powers to compel the disclosure of information, recall drugs and devices, impose fines and injunctions, and collect post-market safety information. The Act amends seriously outdated legislation that had been in place since 1954. While the explicit goals of the Act are to improve patient safety and provide transparency, it also establishes a regulatory framework that facilitates investment in the burgeoning field of biotechnology. While regulatory reform was already on the public agenda, public awareness of litigation against large pharmaceutical firms combined with the championing of the legislation by Conservative MP Terence Young, whose daughter Vanessa died from an adverse drug reaction, pushed the legislation through to implementation. Many key aspects of the Act depend upon the precise nature of supporting regulations that are still to be implemented. Despite the new powers conferred by the legislation on the Minister of Health, there is some concern that these discretionary powers may not be exercised, and that Health Canada may not have sufficient resources to take advantage of these new powers. Given experience to date since enactment, the new legislation, designed to provide greater transparency vis-à-vis therapeutic products, may actually have a chilling effect on independent scrutiny.

  6. Cutting edge: Antimalarial drugs inhibit IFN-β production through blockade of cyclic GMP-AMP synthase-DNA interaction.

    Science.gov (United States)

    An, Jie; Woodward, Joshua J; Sasaki, Tomikazu; Minie, Mark; Elkon, Keith B

    2015-05-01

    Type I IFN is strongly implicated in the pathogenesis of systemic autoimmune diseases, such as lupus, and rare monogenic IFNopathies, including Aicardi-Goutières syndrome. Recently, a new DNA-activated pathway involving the enzyme cyclic GMP-AMP synthase (cGAS) was described and potentially linked to Aicardi-Goutières syndrome. To identify drugs that could potentially inhibit cGAS activity, we performed in silico screening of drug libraries. By computational analysis, we identified several antimalarial drugs (AMDs) that were predicted to interact with the cGAS/dsDNA complex. Our studies validated that several AMDs were effective inhibitors of IFN-β production and that they functioned by inhibiting dsDNA stimulation of cGAS. Because AMDs have been widely used in human diseases and have an excellent safety profile, our findings suggest new therapeutic strategies for the treatment of severe debilitating diseases associated with type I IFNs due to cGAS activation. Copyright © 2015 by The American Association of Immunologists, Inc.

  7. Establishment of in vitro-in vivo equivalence of highly variable drugs - a generic product development perspective.

    Science.gov (United States)

    Pathak, Shriram M; Aggarwal, Deepika; Venkateswarlu, V

    2014-06-01

    In vivo equivalence of highly variable drugs (HVD) has always been a subject of great concern, in terms of both safety and efficacy, for regulatory agencies. Successful demonstration of their bioequivalence thus presents the most crucial component of a generic application, significantly contributing toward the cost and time of development. For poorly soluble drugs, such as telmisartan, dissolution represents the rate-limiting step in the gastric region and in many cases may not be complete, thereby contributing to low and highly variable bioavailability. Consequently, simulation of gastrointestinal conditions is essential to adequately predict the in vivo behavior of drug formulations. In this study, we evaluated usefulness of physiologically relevant dissolution method over commonly used acidic media to forecast comparable in vivo performance of telmisartan formulation to that of reference samples. In the present study, telmisartan was classified as a HVD and a partial replicate design with repeating the reference product and scaling the bioequivalence for the reference variability has been presented. The design has effectively decreased sample size, without increasing patient risk. Results from this project suggest that scaled average bioequivalence (SABE) provides a good approach for evaluating the bioequivalence of HVD, meeting the need for international guidelines for bioequivalence.

  8. A trend analysis of laboratory positive propoxyphene workplace urine drug screens before and after the product recall.

    Science.gov (United States)

    Price, James

    2015-01-01

    Propoxyphene was withdrawn from the US market in November 2010. This drug is still tested for in the workplace as part of expanded panel nonregulated testing. A convenience sample of urine specimens (n = 7838) were provided by workers from various industries. The percentage of positive specimens with 95% confidence intervals was calculated for each year of the study. Logistic regression was used to assess the impact of the year upon the propoxyphene result. The prevalence of positive propoxyphene tests was much higher before the product's withdrawal from the market. Logistic regression provided evidence of a decreasing linear trend (P < 0.000; β = -0.71). The odds ratio signifies that for every additional year the urine specimens were 0.49 times less likely to be positive for propoxyphene. This favors the determination that the change in propoxyphene positive drug test over the years is not by chance. The conclusion supports no longer performing nonregulated workplace propoxyphene urine drug testing for this population.

  9. N-Acetylcysteine enhances the action of anti-inflammatory drugs as suppressors of prostaglandin production in monocytes

    Directory of Open Access Journals (Sweden)

    Erica Hoffer

    2002-01-01

    Full Text Available The anti-inflammatory effect of non-steroidal anti-inflammatory drugs (NSAIDs is associated with inhibition of cyclooxygenase (COX, the rate-limiting enzyme responsible for the synthesis of prostaglandins. Since oxygen free radicals can act as second cellular messengers, especially to modulate the metabolism of arachidonic acid and the prostaglandin tract, it seems plausible that antioxidants might affect the production of prostaglandin by activated cells. This research is focused on the effect of the antioxidant N-acetylcysteine (NAC on the inhibition of prostaglandin E2 formation in activated monocytes by specific and non-specific COX inhibitors. We found that lipopolysaccharide-induced prostaglandin E2 formation was significantly reduced by rofecoxib and by diclofenac, two NSAIDs. Addition of NAC to each of these drugs enhanced the effect of the NSAIDs. These results suggest that one might expect either a potentiation of the anti-inflammatory effect of COX inhibitors by their simultaneous administration with NAC, or obtaining the same anti-inflammatory at lower drug levels.

  10. 76 FR 35672 - Revised Effectiveness Determination; Sunscreen Drug Products for Over-the-Counter Human Use

    Science.gov (United States)

    2011-06-17

    ... who require such products based upon personal knowledge, planned sun exposure, geographical location... identify the appropriate target population (e.g., high altitude skiers or people diagnosed with skin cancer...

  11. Leachables and extractables handbook: safety evaluation, qualification, and best practices applied to inhalation drug products

    National Research Council Canada - National Science Library

    Ball, Douglas J

    2012-01-01

    ...). It discusses best practices for evaluation and management of leachables and extractables throughout the pharma product lifecycle by providing practical knowledge about how and why safety thresholds were developed...

  12. 78 FR 21612 - Medical Device Classification Product Codes; Guidance for Industry and Food and Drug...

    Science.gov (United States)

    2013-04-11

    ... driving force for CDRH's internal organizational structure as well. These Panels were established with the... guidance represents the Agency's current thinking on medical device classification product codes. It does...

  13. Effects of reinforcer magnitude on data-entry productivity in chronically unemployed drug abusers participating in a Therapeutic Workplace.

    Science.gov (United States)

    Wong, Conrad J; Sheppard, Jeannie-Marie; Dallery, Jesse; Bedient, Guy; Robles, Elias; Svikis, Dace; Silverman, Kenneth

    2003-02-01

    The Therapeutic Workplace is a substance abuse treatment wherein patients are hired and paid to work in a job contingent on daily drug-free urine samples. The present study examined data-entry productivity of 6 unemployed methadone patients who demonstrated relatively variable and low data-entry response rates. A within-subject reversal design was used to determine whether increasing reinforcement magnitude tenfold could increase response rates. Four of the 6 participants showed the highest rates of responding in the high magnitude reinforcement condition. Two participants, who had the lowest overall response rates, showed less robust changes to the magnitude manipulation. The results suggest that reinforcement magnitude can be used to improve productivity in Therapeutic Workplace participants.

  14. Ethnopharmacological Approaches for Dementia Therapy and Significance of Natural Products and Herbal Drugs

    Directory of Open Access Journals (Sweden)

    Devesh Tewari

    2018-02-01

    Full Text Available Dementia is a clinical syndrome wherein gradual decline of mental and cognitive capabilities of an afflicted person takes place. Dementia is associated with various risk factors and conditions such as insufficient cerebral blood supply, toxin exposure, mitochondrial dysfunction, oxidative damage, and often coexisting with some neurodegenerative disorders such as Alzheimer's disease (AD, Huntington's disease (HD, and Parkinson's disease (PD. Although there are well-established (semi-synthetic drugs currently used for the management of AD and AD-associated dementia, most of them have several adverse effects. Thus, traditional medicine provides various plant-derived lead molecules that may be useful for further medical research. Herein we review the worldwide use of ethnomedicinal plants in dementia treatment. We have explored a number of recognized databases by using keywords and phrases such as “dementia”, “Alzheimer's,” “traditional medicine,” “ethnopharmacology,” “ethnobotany,” “herbs,” “medicinal plants” or other relevant terms, and summarized 90 medicinal plants that are traditionally used to treat dementia. Moreover, we highlight five medicinal plants or plant genera of prime importance and discuss the physiological effects, as well as the mechanism of action of their major bioactive compounds. Furthermore, the link between mitochondrial dysfunction and dementia is also discussed. We conclude that several drugs of plant origin may serve as promising therapeutics for the treatment of dementia, however, pivotal evidence for their therapeutic efficacy in advanced clinical studies is still lacking.

  15. In vitro production of huperzine A, a promising drug candidate for Alzheimer's disease.

    Science.gov (United States)

    Ma, Xiaoqiang; Gang, David R

    2008-07-01

    Alzheimer's disease (AD) is growing in impact on human health. With no known cure, AD is one of the most expensive diseases in the world to treat. Huperzine A (HupA), a anti-AD drug candidate from the traditional Chinese medicine Qian Ceng Ta (Huperzia serrata), has been shown to be a powerful and selective inhibitor of acetylcholinesterase and has attracted widespread attention because of its unique pharmacological activities and low toxicity. As a result, HupA is becoming an important lead compound for drugs to treat AD. HupA is obtained naturally from very limited and slowly growing natural resources, members of the Huperziaceae. Unfortunately, the content of HupA is very low in the raw plant material. This has led to strong interest in developing sources of HupA. We have developed a method to propagate in vitro tissues of Phlegmariurus squarrosus, a member of the Huperziaceae, that produce high levels of HupA. The in vitro propagated tissues produce even higher levels of HupA than the natural plant, and may represent an excellent source for HupA.

  16. A novel in situ hydrophobic ion paring (HIP) formulation strategy for clinical product selection of a nanoparticle drug delivery system.

    Science.gov (United States)

    Song, Young Ho; Shin, Eyoung; Wang, Hong; Nolan, Jim; Low, Susan; Parsons, Donald; Zale, Stephen; Ashton, Susan; Ashford, Marianne; Ali, Mir; Thrasher, Daniel; Boylan, Nicholas; Troiano, Greg

    2016-05-10

    preclinical efficacy and tolerability data were generated for the pamoic acid lead formulation, which has been selected for evaluation in a Phase 1 clinical trial (ClinicalTrials.gov Identifier NCT 02579226). This work clearly demonstrates the importance of assessing a wide range of drug release rates during formulation screening as a critical step for new drug product development, and how utilizing hydrophobic ion pairing enabled this promising nanoparticle formulation to proceed into clinical development. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics.

    Science.gov (United States)

    Li, Zhaoyang; Easton, Rachael

    2018-01-01

    The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field.

  18. Nonclinical pharmacology and toxicology of the first biosimilar insulin glargine drug product (BASAGLAR®/ABASAGLAR®) approved in the European Union.

    Science.gov (United States)

    Byrd, Richard A; Owens, Rebecca A; Blackbourne, Jamie L; Coutant, David E; Farmen, Mark W; Michael, M Dodson; Moyers, Julie S; Schultze, A Eric; Sievert, Michael K; Tripathi, Niraj K; Vahle, John L

    2017-08-01

    Basaglar ® /Abasaglar ® (Lilly insulin glargine [LY IGlar]) is a long-acting human insulin analogue drug product granted marketing authorisation as a biosimilar to Lantus ® (Sanofi insulin glargine [SA IGlar]) by the European Medicines Agency. We assessed the similarity of LY IGlar to the reference drug product, European Union-sourced SA IGlar (EU-SA IGlar), using nonclinical in vitro and in vivo studies. No biologically relevant differences were observed for receptor binding affinity at either the insulin or insulin-like growth factor-1 (IGF-1) receptors, or in assays of functional or de novo lipogenic activity. The mitogenic potential of LY IGlar and EU-SA IGlar was similar when tested in both insulin- and IGF-1 receptor dominant cell systems. Repeated subcutaneous daily dosing of rats for 4 weeks with 0, 0.3, 1.0, or 2.0 mg/kg LY IGlar and EU-SA IGlar produced mortalities and clinical signs consistent with severe hypoglycaemia. Glucodynamic profiles of LY IGlar and EU-SA IGlar in satellite animals showed comparable dose-related hypoglycaemia. Severe hypoglycaemia was associated with axonal degeneration of the sciatic nerve; the incidence and severity were low and did not differ between LY IGlar and EU-SA IGlar. These results demonstrated no biologically relevant differences in toxicity between LY IGlar and EU-SA IGlar. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics

    Science.gov (United States)

    Easton, Rachael

    2018-01-01

    ABSTRACT The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field. PMID:29035675

  20. Acute drug induced hepatitis secondary to a weight loss product purchased over the internet

    Directory of Open Access Journals (Sweden)

    Cross Tim JS

    2007-06-01

    Full Text Available Abstract Background Many people now seek alternative methods of weight loss. The internet provides a readily available source of weight reduction products, the ingredients of which are often unclear. The authors describe a case of acute hepatitis in a 20 year old woman caused by such a product purchased over the internet. Case Presentation A 20-year old woman presented with a two day history of abdominal pain, vomiting and jaundice. There were no identifiable risk factors for chronic liver disease. Liver function tests demonstrated an acute hepatitis (aminoaspartate transaminase 1230 IU/L. A chronic liver disease screen was negative. The patient had started a weight loss product (Pro-Lean, purchased over the internet two weeks prior to presentation. The patient was treated conservatively, and improved. The sequence of events suggests an acute hepatitis caused by an herbal weight loss product. Conclusion This case report highlights the dangers of weight loss products available to the public over the internet, and the importance of asking specifically about alternative medicines in patients who present with an acute hepatitis.

  1. Zolpidem prescribing practices before and after Food and Drug Administration required product labeling changes.

    Science.gov (United States)

    Norman, Jessica L; Fixen, Danielle R; Saseen, Joseph J; Saba, Laura M; Linnebur, Sunny A

    2017-01-01

    Women have higher morning serum zolpidem concentrations than men after taking an evening dose, potentially leading to increased risk of harm. On 19 April 2013, the United States Food and Drug Administration required labeling changes for zolpidem, recommending an initial dose of no greater than 5 mg (immediate release) or 6.25 mg (controlled release) per night in women. The primary objective of this study was to compare prescribing practices before and after the 2013 zolpidem labeling change. A secondary objective was to evaluate serious adverse events potentially related to zolpidem. Electronic medical records of adults receiving care through the University of Colorado Health system were accessed for study inclusion if patients were provided a first-time prescription for zolpidem either prior to or after the Food and Drug Administration labeling change. Patients were randomly chosen from eight strata based on age, gender, and date of zolpidem initiation (before/after the labeling change). Demographic and zolpidem prescribing data were collected. Low-dose zolpidem was considered 5 mg (immediate release) or 6.25 mg (controlled release) daily or less. Documentation of potentially related serious adverse events within the patients' records was also evaluated. A total of 400 patients were included in the study. The overall percentage of patients prescribed low-dose zolpidem increased from 44% to 58% after the labeling change (p = 0.0020). In a pre-specified subgroup analysis, the percentage of patients prescribed low-dose zolpidem increased in all groups, including young men (38%-50%, p = 0.23), elderly men (34%-40%, p = 0.53), and elderly women (60%-74%, p = 0.14), but the change was only significant in young women (42%-70%, p = 0.0045). After Food and Drug Administration-mandated labeling changes for zolpidem in 2013, the percentage of overall patients in our health system, and specifically young women, with initial prescriptions for low

  2. Zolpidem prescribing practices before and after Food and Drug Administration required product labeling changes

    Directory of Open Access Journals (Sweden)

    Jessica L Norman

    2017-05-01

    Full Text Available Background: Women have higher morning serum zolpidem concentrations than men after taking an evening dose, potentially leading to increased risk of harm. On 19 April 2013, the United States Food and Drug Administration required labeling changes for zolpidem, recommending an initial dose of no greater than 5 mg (immediate release or 6.25 mg (controlled release per night in women. Objectives: The primary objective of this study was to compare prescribing practices before and after the 2013 zolpidem labeling change. A secondary objective was to evaluate serious adverse events potentially related to zolpidem. Methods: Electronic medical records of adults receiving care through the University of Colorado Health system were accessed for study inclusion if patients were provided a first-time prescription for zolpidem either prior to or after the Food and Drug Administration labeling change. Patients were randomly chosen from eight strata based on age, gender, and date of zolpidem initiation (before/after the labeling change. Demographic and zolpidem prescribing data were collected. Low-dose zolpidem was considered 5 mg (immediate release or 6.25 mg (controlled release daily or less. Documentation of potentially related serious adverse events within the patients’ records was also evaluated. Results: A total of 400 patients were included in the study. The overall percentage of patients prescribed low-dose zolpidem increased from 44% to 58% after the labeling change (p = 0.0020. In a pre-specified subgroup analysis, the percentage of patients prescribed low-dose zolpidem increased in all groups, including young men (38%–50%, p = 0.23, elderly men (34%–40%, p = 0.53, and elderly women (60%–74%, p = 0.14, but the change was only significant in young women (42%–70%, p = 0.0045. Conclusion: After Food and Drug Administration–mandated labeling changes for zolpidem in 2013, the percentage of overall patients in our health

  3. Variation in adverse drug reactions listed in product information for antidepressants and anticonvulsants, between the USA and Europe: a comparison review of paired regulatory documents.

    Science.gov (United States)

    Cornelius, Victoria R; Liu, Kun; Peacock, Janet; Sauzet, Odile

    2016-03-20

    To compare consistency of adverse drug reaction (ADR) data in publicly available product information documents for brand drugs, between the USA and Europe. To assess the usefulness of information for prescribers and patients. A comparison review of product information documents for antidepressants and anticonvulsants concurrently marketed by the same pharmaceutical company in the USA and Europe. For each drug, data were extracted from the US Product Inserts and the European Summary of Product Characteristics documents between 09/2013 and 01/2015. Individuals contributing ADR information to product information documents. All ADRs reported in product information sections 5 and 6 (USA), and 4·4 and 4·8 (Europe). Twelve brand drugs--24 paired documents--were included. On average, there were 77 more ADRs reported in the USA compared with in the European product information document, with a median number of 201 ADRs (range: 65-425) and 114 (range: 56-265), respectively. More product information documents in the USA reported information on the source of evidence (10 vs 5) and risk (9 vs 5) for greater than 80% of ADRs included in the document. There was negligible information included regarding duration, severity, reversibility or recurrence of ADRs. On average, only 29% of ADR terms were reported in both paired documents. Product information documents contained a large number of ADRs, but lacked contextual data and information important to patients and prescribers, such as duration, severity and reversibility. The ADR profile was found to be inconsistently reported between the USA and Europe, for the same drug. Identifying, selecting, summarising and presenting multidimensional harm data should be underpinned by practical evidence-based guidelines. In order for prescribers to provide considered risk-benefit advice across competing drug therapies to patients, they need access to comprehensible and reliable ADR information. Published by the BMJ Publishing Group Limited

  4. Adverse events reported to the Food and Drug Administration from 2004 to 2016 for cosmetics and personal care products marketed to newborns and infants.

    Science.gov (United States)

    Cornell, Erika; Kwa, Michael; Paller, Amy S; Xu, Shuai

    2018-03-01

    Despite their ubiquitous use and several recent health controversies involving cosmetics and personal care products for children, the Food and Drug Administration has little oversight of these products and relies on consumer-submitted adverse event reports. We assessed the recently released Center for Food Safety and Applied Nutrition's Adverse Event Reporting System database for adverse event reports submitted to the Food and Drug Administration for baby personal care products and to determine whether useful insights can be derived. We extracted the Center for Food Safety and Applied Nutrition's Adverse Event Reporting System data file from 2004 to 2016 and examined the subset classified according to the Food and Drug Administration-designated product class as a baby product. Events were manually categorized into product type and symptom type to assess for trends. Only 166 total adverse events were reported to the Food and Drug Administration for baby products from 2004 to 2016. The majority of reports indicated rash or other skin reaction; 46% of reported events led to a health care visit. Pediatric dermatologists should consider submitting cosmetics and personal care product adverse event reports and encouraging consumers to do so likewise in situations in which a product adversely affects a child's health. © 2018 Wiley Periodicals, Inc.

  5. RHODIOLA ROSEA: STATUS OF RESEARCH AND POSSIBILITIES FOR COSMECEUTICAL AND DERMATOLOGICAL DRUGS PRODUCTION

    Directory of Open Access Journals (Sweden)

    E. F. Stepanova

    2016-01-01

    Full Text Available Rhodiola rosea is one of the most popular adaptogene agents. Apart from adaptogene, it has the whole range of other pharmaceutical properties: antioxidant, nootropic, antidepressant, immunomodulatory, and other. Russian industry manufactures liquid extract of Rhodiola rosea, as well as food BAS based on the Rhodiola rosea, but there are no dosage forms for external use.The purpose of this work is to analyze scientific information about general characteristics of the pharmacological activity and possible use of Rhodiola rosea in external drugs and cosmetics.Methods. The following resources were used for general characteristic of Rhodiola rosea, its pharmacological properties, particularly the usage of Rhodiola rosea in medical and cosmetic practices, as well prospects of its external use: eLIBRARY, PubMed, Cyberleninca, ResearchGate, information from manufacturers and dealers web-pages.Results. Rhodiola drugs are considered prospective agents for depressions therapy, Parkinson disease treatment, memory, attention defects, for arrhythmia prevention, stamina increase, and stress level decrease in sport and space medicine, for acceptability and efficiency improvement of chemo- and radiotherapy, as immunostimulatory agent. Nowadays in the Russian Federation Rhodiola rosea liquid extract is used as a tonic agent and is prescribed for over-fatigue in healthy persons, and for the sick, weakened as the result of a long-term treatment. Literature has sufficient amount of data about possible effect of biologically active substances of Rhodiola rosea at external use: antioxidant and antimicrobial, bleaching, UV-protective, metabolism stimulating.Conclusion. Thus, the data obtained give evidence about the prospect of Rhodiola use in cosmeceutics and prove the experience of its traditional use for withering and fat skin treatment, as well as acne.

  6. Essential Aspects in Assessing the Safety Impact of Interactions between a Drug Product and Its Associated Manufacturing System.

    Science.gov (United States)

    Jenke, Dennis

    2012-01-01

    An emerging trend in the biotechnology industry is the utilization of plastic components in manufacturing systems for the production of an active pharmaceutical ingredient (API) or a finished drug product (FDP). If the API, the FDP, or any solution used to generate them (for example, process streams such as media, buffers, and the like) come in contact with a plastic at any time during the manufacturing process, there is the potential that substances leached from the plastic may accumulate in the API or FDP, affecting safety and/or efficacy. In this article the author develops a terminology that addresses process streams associated with the manufacturing process. Additionally, the article outlines the safety assessment process for manufacturing systems, specifically addressing the topics of risk management and the role of compendial testing. Finally, the proper use of vendor-supplied extractables information is considered. Manufacturing suites used to produce biopharmaceuticals can include components that are made out of plastics. Thus it is possible that substances could leach out of the plastics and into manufacturing solutions, and it is further possible that such leachables could accumulate in the pharmaceutical product. In this article, the author develops a terminology that addresses process streams associated with the manufacturing process. Additionally, the author proposes a process by which the impact on product safety of such leached substances can be assessed.

  7. Mucosal Immune Regulation in Intestinal Disease. The role of bacterial products, food components and drugs

    NARCIS (Netherlands)

    Bol-Schoenmakers, M.

    2009-01-01

    The challenge of the mucosal gut associated immune system is to remain unresponsive to food products and commensal microbiota, while mounting an appropriate immune response towards pathogens. This implicates the necessity of tight immune regulation within the gut associated lymphoid tissue (GALT).

  8. Stable Production of the Antimalarial Drug Artemisinin in the Moss Physcomitrella patens

    Directory of Open Access Journals (Sweden)

    Nur Kusaira Binti Khairul Ikram

    2017-08-01

    Full Text Available Malaria is a real and constant danger to nearly half of the world’s population of 7.4 billion people. In 2015, 212 million cases were reported along with 429,000 estimated deaths. The World Health Organization recommends artemisinin-based combinatorial therapies, and the artemisinin for this purpose is mainly isolated from the plant Artemisia annua. However, the plant supply of artemisinin is irregular, leading to fluctuation in prices. Here, we report the development of a simple, sustainable, and scalable production platform of artemisinin. The five genes involved in artemisinin biosynthesis were engineered into the moss Physcomitrella patens via direct in vivo assembly of multiple DNA fragments. In vivo biosynthesis of artemisinin was obtained without further modifications. A high initial production of 0.21 mg/g dry weight artemisinin was observed after only 3 days of cultivation. Our study shows that P. patens can be a sustainable and efficient production platform of artemisinin that without further modifications allow for industrial-scale production. A stable supply of artemisinin will lower the price of artemisinin-based treatments, hence become more affordable to the lower income communities most affected by malaria; an important step toward containment of this deadly disease threatening millions every year.

  9. 21st century natural product research and drug development and traditional medicines.

    Science.gov (United States)

    Ngo, Linh T; Okogun, Joseph I; Folk, William R

    2013-04-01

    Natural products and related structures are essential sources of new pharmaceuticals, because of the immense variety of functionally relevant secondary metabolites of microbial and plant species. Furthermore, the development of powerful analytical tools based upon genomics, proteomics, metabolomics, bioinformatics and other 21st century technologies are greatly expediting identification and characterization of these natural products. Here we discuss the synergistic and reciprocal benefits of linking these 'omics technologies with robust ethnobotanical and ethnomedical studies of traditional medicines, to provide critically needed improved medicines and treatments that are inexpensive, accessible, safe and reliable. However, careless application of modern technologies can challenge traditional knowledge and biodiversity that are the foundation of traditional medicines. To address such challenges while fulfilling the need for improved (and new) medicines, we encourage the development of Regional Centres of 'omics Technologies functionally linked with Regional Centres of Genetic Resources, especially in regions of the world where use of traditional medicines is prevalent and essential for health.

  10. Characterization of a mycobacterial cellulase and its impact on biofilm- and drug-induced cellulose production.

    Science.gov (United States)

    Van Wyk, Niël; Navarro, David; Blaise, Mickaël; Berrin, Jean-Guy; Henrissat, Bernard; Drancourt, Michel; Kremer, Laurent

    2017-05-01

    It was recently shown that Mycobacterium tuberculosis produces cellulose which forms an integral part of its extracellular polymeric substances within a biofilm set-up. Using Mycobacterium smegmatis as a proxy model organism, we demonstrate that M. smegmatis biofilms treated with purified MSMEG_6752 releases the main cellulose degradation-product (cellobiose), detected by using ionic chromatography, suggesting that MSMEG_6752 encodes a cellulase. Its overexpression in M. smegmatis prevents spontaneous biofilm formation. Moreover, the method reported here allowed detecting cellobiose when M. smegmatis cultures were exposed to a subinhibitory dose of rifampicin. Overall, this study highlights the role of the MSMEG_6752 in managing cellulose production induced during biofilm formation and antibiotic stress response. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. 21 CFR 341.80 - Labeling of nasal decongestant drug products.

    Science.gov (United States)

    2010-04-01

    ..., diabetes, or difficulty in urination due to enlargement of the prostate gland unless directed by a doctor... identified in § 341.20 (a)(1) through (a)(4) when labeled for children under 12 years of age. (A) “Do not... accompanied by fever, consult a doctor.” (C) “Do not give this product to a child who has heart disease, high...

  12. Progress in nutritional and health profile of milk and dairy products: a novel drug target.

    Science.gov (United States)

    Martemucci, Giovanni; D'Alessandro, Angela Gabriella

    2013-09-01

    There is an increasing focus on diet as a tool to maintain human health and prevent disease. Milk and milk products of ruminants are important source of fat and saturated fatty acids, which are not considered to be very favourable to human health, but are valuable sources of nutrients including bioactive fatty acids (FA), vitamins, and minerals, which can promote positive health effects. The nutritional characteristics of milk and dairy products are related to their composition, which depends on the source species, and varies due to numerous factors, among which the animal diet is the most important. An improvement in milk FA composition and other micronutrients can be reached through an animal feeding strategy. Natural pasture-based farming systems increase microconstituents that are beneficial to human health (CLA, PUFAs, n-3 FAs, antioxidants, vitamins A and E, and Se) and volatile compounds (flavour, and terpenes) in milk and cheese. There are still uncertainties about the health benefits of various milk FAs and other compounds; deep and extensive long-term clinical studies with humans are needed. The contamination of milk and dairy products by heavy metals or dioxins has dramatic negative consequences for human and livestock health and necessitates very urgent consideration and intervention.

  13. Review of Natural Product-Derived Compounds as Potent Antiglioblastoma Drugs

    Directory of Open Access Journals (Sweden)

    Moon Nyeo Park

    2017-01-01

    Full Text Available Common care for glioblastoma multiforme (GBM is a surgical resection followed by radiotherapy and temozolomide- (TMZ- based chemotherapy. Unfortunately, these therapies remain inadequate involving severe mortality and recurrence. Recently, new approaches discovering combinations of multiple inhibitors have been proposed along with the identification of key driver mutations that are specific to each patient. To date, this approach is still limited by the lack of effective therapy. Hopefully, novel compounds derived from natural products are suggested as potential solutions. Inhibitory effects of natural products on angiogenesis and metastasis and cancer suppressive effect of altering miRNA expression are provident discoveries. Angelica sinensis accelerates apoptosis by their key substances influencing factors of apoptosis pathways. Brazilin displays antitumor features by making influence on reactive oxygen species (ROS intensity. Sargassum serratifolium, flavonoids, and so on have antimetastasis effect. Ficus carica controls miRNA that inhibits translation of certain secretory pathway proteins during the UPR. Serratia marcescens and patupilone (EPO 906 are physically assessed materials through clinical trials related to GBM progression. Consequently, our review puts emphasis on the potential of natural products in GBM treatment by regulating multiple malignant cancer-related pathway solving pending problem such as reducing toxicity and side effect.

  14. Production of heparanase constructs suitable for nuclear magnetic resonance and drug discovery studies.

    Science.gov (United States)

    Mosulén, Silvia; Ortí, Leticia; Bas, Esperanza; Carbajo, Rodrigo J; Pineda-Lucena, Antonio

    2011-02-01

    Heparanase is an endo-β-D-glucosidase capable of specifically degrading heparan sulphate, one of the main components of the extracellular matrix. This 65 kDa polypeptide is implicated in cancer processes such as tumour formation, angiogenesis and metastasis, making it a very attractive target in antitumour treatments. Structure-based approaches to find inhibitors of heparanase have been historically hampered by the lack of success in crystallizing the protein. With the aim to undertake the NMR structural characterisation of heparanase, we have designed and produced, using recombinant methods, smaller constructs of heparanase containing the catalytically active glutamic acids and the two binding sites for heparan sulphate. An extensive range of expression and purification conditions were evaluated to alleviate the intrinsic low solubility and aggregation propensity of heparanase, allowing the obtention of the enzyme in milligram quantities, both unlabelled and ¹⁵N-labelled for NMR studies. Using the smallest of the designed constructs and applying NMR and SPR methodologies, we have demonstrated that known inhibitors of heparanase bind to this construct specifically and selectively with K(D) values in the range of those reported for human heparanase, validating it for future drug discovery projects focused on the identification of novel inhibitors of this enzyme. © 2010 Wiley Periodicals, Inc.

  15. Variability in the quality of overdose advice in Summary of Product Characteristics (SPC) documents: gut decontamination recommendations for CNS drugs.

    Science.gov (United States)

    Wall, Andrew J B; Bateman, D N; Waring, W S

    2009-01-01

    Deliberate self-poisoning is a major cause of morbidity and mortality. The Summary of Product Characteristics (SPC) document is a legal requirement for all drugs, and Section 4.9 addresses the features of toxicity and clinical advice on management of overdose. The quality and appropriateness of this advice have received comparatively little attention. Section 4.9 of the SPC was examined for all drugs in the central nervous system (CNS) category of the British National Formulary. Advice concerning gut decontamination was examined with respect to specific interventions: induced vomiting, oral activated charcoal, gastric lavage, and other interventions. Data were compared with standard reference sources for clinical management advice in poisoning. These were graded 'A' if no important differences existed, 'B' if differences were noted but not thought clinically important, and 'C' if differences were thought to be clinically significant. SPC documents were examined for 258 medications from 67 manufacturers. The overall agreement was 'A' in 23 (8.9%), 'B' in 28 (10.9%) and 'C' in 207 (80.2%). Discrepancies were due to inappropriate recommendation of induced emesis in 21.7% (95% confidence interval 17.1, 27.1), gastric lavage in 38.4% (32.7, 44.4), other gut decontamination in 5.8% (3.6, 9.4) and failure to recommend oral activated charcoal in 57.4% (51.1, 63.4). Gut decontamination advice in SPC documents with respect to CNS drugs was inadequate. Possible reasons for the observed discrepancies and ways of improving the consistency of advice are proposed.

  16. Identification of transformation products of antiviral drugs formed during biological wastewater treatment and their occurrence in the urban water cycle.

    Science.gov (United States)

    Funke, Jan; Prasse, Carsten; Ternes, Thomas A

    2016-07-01

    The fate of five antiviral drugs (abacavir, emtricitabine, ganciclovir, lamivudine and zidovudine) was investigated in biological wastewater treatment. Investigations of degradation kinetics were accompanied by the elucidation of formed transformation products (TPs) using activated sludge lab experiments and subsequent LC-HRMS analysis. Degradation rate constants ranged between 0.46 L d(-1) gSS(-1) (zidovudine) and 55.8 L d(-1) gSS(-1) (abacavir). Despite these differences of the degradation kinetics, the same main biotransformation reaction was observed for all five compounds: oxidation of the terminal hydroxyl-moiety to the corresponding carboxylic acid (formation of carboxy-TPs). In addition, the oxidation of thioether moieties to sulfoxides was observed for emtricitabine and lamivudine. Antiviral drugs were detected in influents of municipal wastewater treatment plants (WWTPs) with concentrations up to 980 ng L(-1) (emtricitabine), while in WWTP effluents mainly the TPs were found with concentration levels up to 1320 ng L(-1) (carboxy-abacavir). Except of zidovudine none of the original antiviral drugs were detected in German rivers and streams, whereas the concentrations of the TPs ranged from 16 ng L(-1) for carboxy-lamivudine up to 750 ng L(-1) for carboxy-acyclovir. These concentrations indicate an appreciable portion from WWTP effluents present in rivers and streams, as well as the high environmental persistence of the carboxy-TPs. As a result three of the carboxylic TPs were detected in finished drinking water. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Emulsion centrifugal spinning for production of 3D drug releasing nanofibres with core/shell structure

    Czech Academy of Sciences Publication Activity Database

    Buzgo, M.; Rampichová, Michala; Vocetková, Karolína; Sovková, Věra; Lukášová, Věra; Doupnik, M.; Míčková, Andrea; Rustichelli, Franco; Amler, Evžen

    2017-01-01

    Roč. 7, č. 3 (2017), s. 1215-1228 ISSN 2046-2069 R&D Projects: GA ČR(CZ) GA15-15697S; GA MŠk(CZ) LO1309; GA MŠk(CZ) LO1508 Institutional support: RVO:68378041 Keywords : platelet-rich plasma * tissue engineering applications * oscillatory shear measurements * epidermal-growth-factor Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Bioproducts (products that are manufactured using biological material as feedstock) biomaterials, bioplastics, biofuels, bioderived bulk and fine chemicals, bio-derived novel materials Impact factor: 3.108, year: 2016

  18. HIV antiretroviral drug combination induces endothelial mitochondrial dysfunction and reactive oxygen species production, but not apoptosis

    International Nuclear Information System (INIS)

    Jiang Bo; Hebert, Valeria Y.; Li, Yuchi; Mathis, J. Michael; Alexander, J. Steven; Dugas, Tammy R.

    2007-01-01

    Numerous reports now indicate that HIV patients administered long-term antiretroviral therapy (ART) are at a greater risk for developing cardiovascular diseases. Endothelial dysfunction is an initiating event in atherogenesis and may contribute to HIV-associated atherosclerosis. We previously reported that ART induces direct endothelial dysfunction in rodents. In vitro treatment of human umbilical vein endothelial cells (HUVEC) with ART indicated endothelial mitochondrial dysfunction and a significant increase in the production of reactive oxygen species (ROS). In this study, we determined whether ART-induced endothelial dysfunction is mediated via mitochondria-derived ROS and whether this mitochondrial injury culminates in endothelial cell apoptosis. Two major components of ART combination therapy, a nucleoside reverse transcriptase inhibitor and a protease inhibitor, were tested, using AZT and indinavir as representatives for each. Microscopy utilizing fluorescent indicators of ROS and mitochondria demonstrated the mitochondrial localization of ART-induced ROS. MnTBAP, a cell-permeable metalloporphyrin antioxidant, abolished ART-induced ROS production. As a final step in confirming the mitochondrial origin of the ART-induced ROS, HUVEC were transduced with a cytosolic- compared to a mitochondria-targeted catalase. Transduction with the mitochondria-targeted catalase was more effective than cytoplasmic catalase in inhibiting the ROS and 8-isoprostane (8-iso-PGF 2α ) produced after treatment with either AZT or indinavir. However, both mitochondrial and cytoplasmic catalase attenuated ROS and 8-iso-PGF 2α production induced by the combination treatment, suggesting that in this case, the formation of cytoplasmic ROS may also occur, and thus, that the mechanism of toxicity in the combination treatment group may be different compared to treatment with AZT or indinavir alone. Finally, to determine whether ART-induced mitochondrial dysfunction and ROS production

  19. Border between natural product and drug: Comparison of the related benzoquinones idebenone and coenzyme Q10

    Directory of Open Access Journals (Sweden)

    Nuri Gueven

    2015-04-01

    Full Text Available Coenzyme Q10 is a ubiquitous component of cellular membranes and belongs to the class of benzoquinones that mainly differ with regards to the length and composition of their hydrophobic tail. The characteristic quinone group can accept electrons from various biological sources and is converted by a one electron transfer to the unstable semiquinone or by a two electron transfer to the more stable hydroquinone. This feature makes CoQ10 the bona fide cellular electron transfer molecule within the mitochondrial respiratory chain and also makes it a potent cellular antioxidant. These activities serve as justification for its popular use as food supplement. Another quinone with similarities to the naturally occurring CoQ10 is idebenone, which shares its quinone moiety with CoQ10, but at the same time differs from CoQ10 by the presence of a much shorter, less lipophilic tail. However, despite its similarity to CoQ10, idebenone cannot be isolated from any natural sources but instead was synthesized and selected as a pharmacologically active compound in the 1980s by Takeda Pharmaceuticals purely based on its pharmacological properties. Several recent clinical trials demonstrated some therapeutic efficacy of idebenone in different indications and as a consequence, many practitioners question if the freely available CoQ10 could not be used instead. Here, we describe the molecular and pharmacological features of both molecules that arise from their structural differences to answer the question if idebenone is merely a CoQ10 analogue as frequently perpetuated in the literature or a pharmaceutical drug with entirely different features.

  20. Trends in Deaths Involving Heroin and Synthetic Opioids Excluding Methadone, and Law Enforcement Drug Product Reports, by Census Region - United States, 2006-2015.

    Science.gov (United States)

    O'Donnell, Julie K; Gladden, R Matthew; Seth, Puja

    2017-09-01

    Opioid overdose deaths quadrupled from 8,050 in 1999 to 33,091 in 2015 and accounted for 63% of drug overdose deaths in the United States in 2015. During 2010-2015, heroin overdose deaths quadrupled from 3,036 to 12,989 (1). Sharp increases in the supply of heroin and illicitly manufactured fentanyl (IMF) are likely contributing to increased deaths (2-6). CDC examined trends in unintentional and undetermined deaths involving heroin or synthetic opioids excluding methadone (i.e., synthetic opioids)* by the four U.S. Census regions during 2006-2015. Drug exhibits (i.e., drug products) obtained by law enforcement and reported to the Drug Enforcement Administration's (DEA's) National Forensic Laboratory Information System (NFLIS) that tested positive for heroin or fentanyl (i.e., drug reports) also were examined. All U.S. Census regions experienced substantial increases in deaths involving heroin from 2006 to 2015. Since 2010, the South and West experienced increases in heroin drug reports, whereas the Northeast and Midwest experienced steady increases during 2006-2015. † In the Northeast, Midwest, and South, deaths involving synthetic opioids and fentanyl drug reports increased considerably after 2013. These broad changes in the U.S. illicit drug market highlight the urgent need to track illicit drugs and enhance public health interventions targeting persons using or at high risk for using heroin or IMF.

  1. Comprehensive validation scheme for in situ fiber optics dissolution method for pharmaceutical drug product testing.

    Science.gov (United States)

    Mirza, Tahseen; Liu, Qian Julie; Vivilecchia, Richard; Joshi, Yatindra

    2009-03-01

    There has been a growing interest during the past decade in the use of fiber optics dissolution testing. Use of this novel technology is mainly confined to research and development laboratories. It has not yet emerged as a tool for end product release testing despite its ability to generate in situ results and efficiency improvement. One potential reason may be the lack of clear validation guidelines that can be applied for the assessment of suitability of fiber optics. This article describes a comprehensive validation scheme and development of a reliable, robust, reproducible and cost-effective dissolution test using fiber optics technology. The test was successfully applied for characterizing the dissolution behavior of a 40-mg immediate-release tablet dosage form that is under development at Novartis Pharmaceuticals, East Hanover, New Jersey. The method was validated for the following parameters: linearity, precision, accuracy, specificity, and robustness. In particular, robustness was evaluated in terms of probe sampling depth and probe orientation. The in situ fiber optic method was found to be comparable to the existing manual sampling dissolution method. Finally, the fiber optic dissolution test was successfully performed by different operators on different days, to further enhance the validity of the method. The results demonstrate that the fiber optics technology can be successfully validated for end product dissolution/release testing. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

  2. Policy and health implications of using the U.S. Food and Drug Administration product design approach in reducing tobacco product risk.

    Science.gov (United States)

    Givel, Michael

    2008-06-01

    Purported risk or harm reduction through product design change of cigarettes has occurred in three phases in the U.S. The first phase from the 1940s to the early 1960s included a gradual rise in filtered cigarettes. The second phase, which began in the early 1960s in response to the landmark 1964 U.S. Surgeon General's report that linked smoking with lung cancer and other diseases, included the introduction of purportedly low tar and nicotine cigarettes. Subsequent research found that both filters and low tar and nicotine cigarettes were ineffective approaches to reducing health risks associated with smoking. Despite this, these product design changes were used in tobacco industry marketing campaigns to allay consumer health concerns and stabilize tobacco markets and sales. Since 2004, a new risk or harm reduction phase has occurred with the backing by Philip Morris as well as major U.S. health groups of U.S. Food and Drug Administration legislation that would require disclosure of tobacco ingredients, ban misleading health claims, prohibit or reduce harmful ingredients, and require prior approval of tobacco design, performance changes, and modified risk tobacco products. However, current scientific literature indicates that there is no scientific consensus and little evidence on what tobacco ingredients are linked to particular morbidities and mortalities and at what levels. This will allow the tobacco industry to implicitly or explicitly claim their products are "safer." Instead, health advocates should advocate for scientifically proven policy measures such as smoke free public places or higher tobacco taxes that control and reduce tobacco markets and consumption.

  3. Drug product immobilization in recycled polyethylene/polypropylene reclaimed from municipal solid waste: experimental and numerical assessment.

    Science.gov (United States)

    Saad, Walid; Slika, Wael; Mawla, Zara; Saad, George

    2017-12-01

    Recently, there has been a growing interest in identifying suitable routes for the disposal of pharmaceutical wastes. This study investigates the potential of matrix materials composed of recycled polyethylene/polypropylene reclaimed from municipal solid wastes at immobilizing pharmaceutical solid wastes. Diclofenac (DF) drug product was embedded in boards of recycled plastic material, and leaching in water was assessed at various temperatures. DF concentrations were determined by high-performance liquid chromatography and revealed a maximum leachable fraction of 4% under accelerated conditions of 70°C, and less than 0.3% following 39 days of exposure at 20°C. The Ensemble Kalman Filter was employed to characterize the leaching behavior of DF. The filter verified the occurrence of leaching through diffusion, and was successful in predicting the leaching behavior of DF at 50°C and 70°C.

  4. Incorporating Natural Products, Pharmaceutical Drugs, Self-Care and Digital/Mobile Health Technologies into Molecular-Behavioral Combination Therapies for Chronic Diseases

    Science.gov (United States)

    Bulaj, Grzegorz; Ahern, Margaret M.; Kuhn, Alexis; Judkins, Zachary S.; Bowen, Randy C.; Chen, Yizhe

    2016-01-01

    Merging pharmaceutical and digital (mobile health, mHealth) ingredients to create new therapies for chronic diseases offers unique opportunities for natural products such as omega-3 polyunsaturated fatty acids (n-3 PUFA), curcumin, resveratrol, theanine, or α-lipoic acid. These compounds, when combined with pharmaceutical drugs, show improved efficacy and safety in preclinical and clinical studies of epilepsy, neuropathic pain, osteoarthritis, depression, schizophrenia, diabetes and cancer. Their additional clinical benefits include reducing levels of TNFα and other inflammatory cytokines. We describe how pleiotropic natural products can be developed as bioactive incentives within the network pharmacology together with pharmaceutical drugs and self-care interventions. Since approximately 50% of chronically-ill patients do not take pharmaceutical drugs as prescribed, psychobehavioral incentives may appeal to patients at risk for medication non-adherence. For epilepsy, the incentive-based network therapy comprises anticonvulsant drugs, antiseizure natural products (n-3 PUFA, curcumin or/and resveratrol) coupled with disease-specific behavioral interventions delivered by mobile medical apps. The add-on combination of antiseizure natural products and mHealth supports patient empowerment and intrinsic motivation by having a choice in self-care behaviors. The incentivized therapies offer opportunities: (1) to improve clinical efficacy and safety of existing drugs, (2) to catalyze patient-centered, disease self-management and behavior-changing habits, also improving health-related quality-of-life after reaching remission, and (3) merging copyrighted mHealth software with natural products, thus establishing an intellectual property protection of medical treatments comprising the natural products existing in public domain and currently promoted as dietary supplements. Taken together, clinical research on synergies between existing drugs and pleiotropic natural products

  5. Phosphodiesterase (PDE5) inhibition assay for rapid detection of erectile dysfunction drugs and analogs in sexual enhancement products.

    Science.gov (United States)

    Santillo, Michael F; Mapa, Mapa S T

    2018-02-28

    Products marketed as dietary supplements for sexual enhancement are frequently adulterated with phosphodiesterase-5 (PDE5) inhibitors, which are erectile dysfunction drugs or their analogs that can cause adverse health effects. Due to widespread adulteration, a rapid screening assay was developed to detect PDE5 inhibitors in adulterated products. The assay employs fluorescence detection and is based on measuring inhibition of PDE5 activity, the pharmacological mechanism shared among the adulterants. Initially, the assay reaction scheme was established and characterized, followed by analysis of 9 representative PDE5 inhibitors (IC 50 , 0.4-4.0 ng mL -1 ), demonstrating sensitive detection in matrix-free solutions. Next, dietary supplements serving as matrix blanks (n = 25) were analyzed to determine matrix interference and establish a threshold value; there were no false positives. Finally, matrix blanks were spiked with 9 individual PDE5 inhibitors, along with several mixtures. All 9 adulterants were successfully detected (≤ 5 % false negative rate; n = 20) at a concentration of 1.00 mg g -1 , which is over 5 times lower than concentrations commonly encountered in adulterated products. A major distinction of the PDE5 inhibition assay is the ability to detect adulterants without prior knowledge of their chemical structures, demonstrating a broad-based detection capability that can address a continuously evolving threat of new adulterants. The PDE5 inhibition assay can analyze over 40 samples simultaneously within 15 minutes and involves a single incubation step and simple data analysis, all of which are advantageous for combating the widespread adulteration of sex-enhancement products. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

  6. Documentation of pediatric drug safety in manufacturers' product monographs: a cross-sectional evaluation of the canadian compendium of pharmaceuticals and specialities.

    Science.gov (United States)

    Uppal, Navjeet K; Dupuis, Lee L; Parshuram, Christopher S

    2008-01-01

    To describe the provision of pediatric drug safety information in a national formulary of manufacturers' drug product monographs. We performed a cross-sectional evaluation of comprehensive product monographs contained in the 2005 Canadian Compendium of Pharmaceuticals and Specialities (CPS). We abstracted data describing indications for prescription, statements about pediatric safety, available preparations, and provision of dosing guidelines. For each monograph we classified pediatric safety data as either present, present but limited or absent. We then described the pediatric safety data in CPS monographs for drugs listed in the published formulary of the Hospital for Sick Children, Toronto, Ontario, Canada. A total of 2232 product monographs were screened; 684 were excluded and 1548 (66%) were further analyzed. 1462 (94%) had indications that did not exclude children. Pediatric safety information was present in 592 (38%), present but limited in 148 (10%), and absent in 808 (52%) drug monographs. Safety statements were absent in 224 (14%) drug monographs that provided both dosing guidelines and formulations suitable for administration to children, and in 214 (52%) of 411 drugs in the pediatric hospital formulary. We evaluated a widely available national source of pediatric prescribing information. Safety data for children was not mentioned in more than half of the product monographs. Moreover, the provision of safety data was discordant with indications for prescription, the availability of pediatric formulations, and dosing guidelines within the monographs, and with inclusion in a pediatric hospital formulary. Our study suggests that the presentation of pediatric safety data in drug product monographs can be improved to better inform prescribing and to optimize pharmacotherapy in children.

  7. Active packaging for topical cosmetic/drug products: a hot-melt extruded preservative delivery device.

    Science.gov (United States)

    Zema, L; Sangalli, M E; Maroni, A; Foppoli, A; Bettero, A; Gazzaniga, A

    2010-06-01

    A delivery device intended for the prolonged release of antimicrobial agents, able to enhance the stability profile of liquid/semi-solid cosmetic/pharmaceutical products for topical application, was proposed in the present study. With the aid of a simulation program based on compartment models, the relevant kinetic and formulation parameters were defined using dehydroacetic acid sodium salt (DHA.Na, Prevan) as the model preservative. Indeed, the overall DHA.Na degradation rate is increased in the presence of formaldehyde releasers that are often employed as co-preservatives. Inert matrices (3 g weight and 18 mm diameter) based on high-density polyethylene (HDPE), possibly consistent with the design of an active packaging meant for preservative delivery, were prepared by hot-melt extrusion. Units with satisfactory physical-technological properties could be obtained up to 50%w/w loads of antimicrobial agent. In an attempt to modify the relevant Fickian release profiles by varying the area exposed to the medium, matrix systems coated with an impermeable film except for one base (CMs) or for the inner surface of a central drilled hole (PCMs) were investigated. On the basis of the n exponent of power equation and the outcome of linear fitting, PCMs were proven able to yield the zero-order release behaviour needed to ensure constant DHA.Na levels over a predetermined time period, as indicated by the simulation process. Copyright 2010 Elsevier B.V. All rights reserved.

  8. Development of natural products as drugs acting on central nervous system

    Directory of Open Access Journals (Sweden)

    Xing-Zu Zhu

    1991-01-01

    Full Text Available We have recenty studied several natural product constituents which have effects on the CNS. (1 Tetrahydropalmatine (THP and its analogues were isolated from Corydalis ambigua and various species of Stephania. (+-THP and (--THP posses not only analgesic activity, but also exert sedative-tranquillizing and hypnotic actions. Results of receptor binding assay and their pre-and post-synaptic effects on dopaminergic system indicate that (--THP and (--stepholidine are dopamine receptor antagonists while (+-THP is a selective dopamine depletor. (2 3-Acetylaconitine (AAC is an alkaloid isolated from Aconitum flavum. The relative potency of analgesic action of AAC was 5.1-35.6 and 1250-3912 times that of morphine and aspirin, respectively. The analgesic effect of AAC was antagonized by naloxone, but was eliminated by reserpine. In monkeys, after AAC was injected for 92 days, no abstinence syndrome was seen after sudden AAC withdrawal or when challenged with nalorphine. (3 Huperzine A (Hup-A is an alkaloid isolated from Huperzia serrata which was found to be a selective ChE inhibitor and could improve learning and retrieval process. Preliminary clinical studies showed that Hup-A improve short-and long-term memory in patients of cerebral arteriosclerosis with memory impairment. (4 Ranamargarin is a new tetradecapeptide isolated from the skin of the Chines frog Rana margaratae. This peptide may mainly act on NK-1 receptor.

  9. Palm oil based polyols for acrylated polyurethane production

    International Nuclear Information System (INIS)

    Rida Tajau; Mohd Hilmi Mahmood; Mek Zah Salleh; Khairul Zaman Mohd Dahlan; Rosley Che Ismail

    2006-01-01

    Palm oil becomes important renewable resources for the production of polyols for the polyurethane manufacturing industry. The main raw materials used for the production of acrylated polyurethane are polyols, isocyanates and hydroxyl terminated acrylate compounds. In these studies, polyurethane based natural polymer (palm oil), i.e., POBUA (Palm Oil Based Urethane Acrylate) were prepared from three different types of palm oil based polyols i.e., epoxidised palm oil (EPOP), palm oil oleic acid and refined, bleached and deodorized (RBD) palm olein based polyols. The performances of these three acrylated polyurethanes when used for coatings and adhesives were determined and compared with each other. (Author)

  10. Self-reported cannabis products and other illicit drugs consumption in older school-age children in Northern Lithuania: a comparison between 2006 and 2012.

    Science.gov (United States)

    Miniauskienė, Dalia; Jurgaitienė, Dalia; Strukčinskienė, Birutė

    2014-01-01

    Cannabis use is widespread among young people in Europe. The aim of this study was to analyze and to compare the associations between the self-reported consumption of cannabis products and other illicit drugs among older schoolchildren in 2006 and in 2012. Two cross-sectional surveys were conducted in 2006 and 2012 in Northern Lithuania. In total 3447 young people aged 17-19 years were investigated (1585 male and 1862 female). For this survey, the ESPAD questionnaire was used. In Northern Lithuania, the schoolchildren aged 17-19 years self-reported that 16.7% in 2006 and 23.9% in 2012 of them tried cannabis products. The consumption of cannabis products in the age group of 17 years increased from 14.9% in 2006 to 21.5% in 2012. The consumption of cannabis together with alcohol increased from 7.6% to 14.3%. Cannabis consumers more often tried amphetamines, heroin, LSD, cocaine, crack, ecstasy, hallucinogenic mushrooms, and injective drugs. In 2012, cannabis consumers girls less than boys used only crack and injective drugs; all other illicit drugs they used the same often as boys. The cannabis products consumption in schoolchildren has increased by 7%. Nearly twofold increase was observed in the consumption of cannabis together with alcohol. Young people who used cannabis products more often tried other illicit drugs. There were no differences by gender in the consumption of illicit drugs among cannabis consumers. Copyright © 2014 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  11. Quality Characteristics of Iranian Extra Virgin Flaxseed Oil and the Effect of the Refining Stages before Deodorization on its Physicochemical Properties

    Directory of Open Access Journals (Sweden)

    Manochehr Bahmaei

    2017-03-01

    Full Text Available Flaxseed oil is known as a functional oil because of the high content of α-linolenic acid; therefore, the aim of this research was to investigate some physicochemical properties of Iranian extra virgin flaxseed oil (EVFO and the impact of the refining stages before deodorization on these properties. Fatty acid composition, peroxide and anisidine values, free fatty acids, Crystallization point, chlorophyll content, β-carotene content, and color were analyzed. The Iranian flaxseed oils had about 39-40% omega-3 fatty acids and a low ratio of omega-6 to omega-3 and equal to 0.44-0.47, which can be combined with oils rich in omega-6 to reach a favorite omega-6 to omega-3 ratio. In addition, the results showed that when EVFO was refined, the crystallization thermograms changed significantly. The presence of phospholipid compounds in EVFO made its onset, crystallization, endset points higher than the RFO. The amount of β-carotene and chlorophyll content of refined flaxseed oil (RFO were 6 and 22.33 times lower than its EVFO. Also, RFO had significantly (p<0.05 more L*, less tendency to yellow color, and tendency to a green color as compared to its EVFO. The results showed that flaxseed oil fatty acid content, free fatty acids, peroxide, Anisdine values, crystallization temperature, chlorophyll and β-carotene content and the color were significantly affected by the refining stages. So it is recommended that flaxseed oil not to be refined, but be used in a short time period. Also, it should be consumed in blending with omega-6 oils (in order to maintain omega-6 to omega-3 ratio.

  12. Generic Drugs: Questions and Answers

    Science.gov (United States)

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Drugs Home Drugs Resources for You Information for Consumers (Drugs) Questions & Answers Generic Drugs: Questions & Answers Share Tweet Linkedin Pin it More ...

  13. Multi-channel counter-current chromatography for high-throughput fractionation of natural products for drug discovery.

    Science.gov (United States)

    Wu, Shihua; Yang, Lu; Gao, Yuan; Liu, Xiaoyue; Liu, Feiyan

    2008-02-08

    A multi-channel counter-current chromatography (CCC) method has been designed and fabricated for the high-throughput fractionation of natural products without complications sometimes encountered with other conventional chromatographic systems, such as irreversible adsorptive constituent losses and deactivation, tailing of solute peaks and contamination. It has multiple independent CCC channels and each channel connects independent separation column(s) by parallel flow tubes, and thus the multi-channel CCC apparatus can achieve simultaneously two or more independent chromatographic processes. Furthermore, a high-throughput CCC fractionation method for natural products has been developed by a combination of a new three-channel CCC apparatus and conventional parallel chromatographic devices including pumps, sample injectors, effluent detectors and collectors, and its performance has been displayed on the fractionation of ethyl acetate extracts of three natural materials Solidago canadensis, Suillus placidus, and Trichosanthes kirilowii, which are found to be potent cytotoxic to tumor cell lines in the course of screening the antitumor candidates. By combination of biological screening programs and preparative high-performance liquid chromatography (HPLC) purification, 22.8 mg 6 beta-angeloyloxykolavenic acid and 29.4 mg 6 beta-tigloyloxykolavenic acid for S. canadensis, 25.3mg suillin for S. placidus, and 6.8 mg 23,24-dihydrocucurbitacin B for T. Kirilowii as their major cytotoxic principles were isolated from each 1000 mg crude ethyl acetate extract. Their chemical structures were characterized by electrospray ionization mass spectrometry, one- and two-dimensional nuclear magnetic resonance. The overall results indicate the multi-channel CCC is very useful for high-throughput fractionation of natural products for drug discovery in spite of the solvent balancing requirement and the lower resolution of the shorter CCC columns.

  14. 76 FR 7743 - Professional Labeling for Laxative Drug Products for Over-the-Counter Human Use; Proposed...

    Science.gov (United States)

    2011-02-11

    ... enzyme inhibitor; a prescription drug for hypertension. Acute phosphate nephropathy means a type of... abbreviation for angiotension receptor blocker, a prescription drug for hypertension. Biologic plausibility...] unstable angina [cir] preexisting electrolyte disturbances (such as dehydration, or those secondary to the...

  15. VirtualToxLab — A platform for estimating the toxic potential of drugs, chemicals and natural products

    Energy Technology Data Exchange (ETDEWEB)

    Vedani, Angelo, E-mail: angelo.vedani@unibas.ch [Biographics Laboratory 3R, Klingelbergstrasse 50, 4056 Basel (Switzerland); Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel (Switzerland); Dobler, Max [Biographics Laboratory 3R, Klingelbergstrasse 50, 4056 Basel (Switzerland); Smieško, Martin [Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel (Switzerland)

    2012-06-01

    The VirtualToxLab is an in silico technology for estimating the toxic potential (endocrine and metabolic disruption, some aspects of carcinogenicity and cardiotoxicity) of drugs, chemicals and natural products. The technology is based on an automated protocol that simulates and quantifies the binding of small molecules towards a series of proteins, known or suspected to trigger adverse effects. The toxic potential, a non-linear function ranging from 0.0 (none) to 1.0 (extreme), is derived from the individual binding affinities of a compound towards currently 16 target proteins: 10 nuclear receptors (androgen, estrogen α, estrogen β, glucocorticoid, liver X, mineralocorticoid, peroxisome proliferator-activated receptor γ, progesterone, thyroid α, and thyroid β), four members of the cytochrome P450 enzyme family (1A2, 2C9, 2D6, and 3A4), a cytosolic transcription factor (aryl hydrocarbon receptor) and a potassium ion channel (hERG). The interface to the technology allows building and uploading molecular structures, viewing and downloading results and, most importantly, rationalizing any prediction at the atomic level by interactively analyzing the binding mode of a compound with its target protein(s) in real-time 3D. The VirtualToxLab has been used to predict the toxic potential for over 2500 compounds: the results are posted on (http://www.virtualtoxlab.org). The free platform — the OpenVirtualToxLab — is accessible (in client–server mode) over the Internet. It is free of charge for universities, governmental agencies, regulatory bodies and non-profit organizations. -- Highlights: ► In silico technology for estimating the toxic potential of drugs and chemicals. ► Simulation of binding towards 16 proteins suspected to trigger adverse effects. ► Mechanistic interpretation and real-time 3D visualization. ► Accessible over the Internet. ► Free of charge for universities, governmental agencies, regulatory bodies and NPOs.

  16. VirtualToxLab — A platform for estimating the toxic potential of drugs, chemicals and natural products

    International Nuclear Information System (INIS)

    Vedani, Angelo; Dobler, Max; Smieško, Martin

    2012-01-01

    The VirtualToxLab is an in silico technology for estimating the toxic potential (endocrine and metabolic disruption, some aspects of carcinogenicity and cardiotoxicity) of drugs, chemicals and natural products. The technology is based on an automated protocol that simulates and quantifies the binding of small molecules towards a series of proteins, known or suspected to trigger adverse effects. The toxic potential, a non-linear function ranging from 0.0 (none) to 1.0 (extreme), is derived from the individual binding affinities of a compound towards currently 16 target proteins: 10 nuclear receptors (androgen, estrogen α, estrogen β, glucocorticoid, liver X, mineralocorticoid, peroxisome proliferator-activated receptor γ, progesterone, thyroid α, and thyroid β), four members of the cytochrome P450 enzyme family (1A2, 2C9, 2D6, and 3A4), a cytosolic transcription factor (aryl hydrocarbon receptor) and a potassium ion channel (hERG). The interface to the technology allows building and uploading molecular structures, viewing and downloading results and, most importantly, rationalizing any prediction at the atomic level by interactively analyzing the binding mode of a compound with its target protein(s) in real-time 3D. The VirtualToxLab has been used to predict the toxic potential for over 2500 compounds: the results are posted on (http://www.virtualtoxlab.org). The free platform — the OpenVirtualToxLab — is accessible (in client–server mode) over the Internet. It is free of charge for universities, governmental agencies, regulatory bodies and non-profit organizations. -- Highlights: ► In silico technology for estimating the toxic potential of drugs and chemicals. ► Simulation of binding towards 16 proteins suspected to trigger adverse effects. ► Mechanistic interpretation and real-time 3D visualization. ► Accessible over the Internet. ► Free of charge for universities, governmental agencies, regulatory bodies and NPOs.

  17. Anti-tuberculosis drug combination for controlled oral delivery using 3D printed compartmental dosage forms: From drug product design to in vivo testing

    DEFF Research Database (Denmark)

    Genina, Natalja; Boetker, Johan Peter; Colombo, Stefano

    2017-01-01

    for treatment of tuberculosis (TB) that negatively interact with each other upon simultaneous release in acidic environment. The dcDUs were designed in silico by computer aided design (CAD) and fabricated in two steps; first three-dimensional (3D) printing of the outer structure, followed by hot-melt extrusion...... (HME) of the drug-containing filaments. The structure of the fabricated dcDUs was visualized by scanning electron microscopy (SEM). The 3D printed compartmentalized shells were loaded with filaments containing active pharmaceutical ingredient (API) and selectively sealed to modulate drug dissolution...

  18. The use of the United States FDA programs as a strategy to advance the development of drug products for neglected tropical diseases.

    Science.gov (United States)

    Sachs-Barrable, Kristina; Conway, Jocelyn; Gershkovich, Pavel; Ibrahim, Fady; Wasan, Kishor M

    2014-11-01

    Neglected tropical diseases (NTDs) are infections which are endemic in poor populations in lower- and middle-income countries (LMIC). Approximately one billion people have now or are at risk of getting an NTD and yet less than 5% of research dollars are focused on providing treatments and prevention of these highly debilitating and deadly conditions. The United States Food and Drug Administration (FDA) Orphan Drug Designation program (ODDP) provides orphan status to drugs and biologics, defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases and/or disorders that affect fewer than 200 000 people in the United States, or that affect more than 200 000 persons but are not expected to recover the costs of developing and marketing a treatment drug. These regulations have led to the translation of rare disease knowledge into innovative rare disease therapies. The FDA Guidance for Industry on developing drugs for the treatment and prevention of NTDs describes the following regulatory strategies: Orphan Product Designation, Fast Track Designation, Priority Review Designation, Accelerated Approval and Tropical Disease Priority Review Voucher. This paper will discuss how these regulations and especially the ODDP can improve the clinical development and accessibility of drug products for NTDs.

  19. A simultaneous determination of related substances by high performance liquid chromatography in a drug product using quality by design approach.

    Science.gov (United States)

    Tol, Trupti; Kadam, Nilesh; Raotole, Nilesh; Desai, Anita; Samanta, Gautam

    2016-02-05

    The combination of Abacavir, Lamivudine and Dolutegravir is an anti-retroviral formulation that displays high efficacy and superiority in comparison to other anti-retroviral combinations. Analysis of related substances in this combination drug product was very challenging due to the presence of nearly thirty peaks including the three active pharmaceutical ingredients (APIs), eleven known impurities and other pharmaceutical excipients. Objective of this study was to develop a single, selective, and robust high performance liquid chromatography method for the efficient separation of all peaks. Initially, one-factor-at-a-time (OFAT) approach was adopted to develop the method. But, it could not resolve all the critical peaks in such complex matrix. This led to the advent of two different HPLC methods for the determination of related substances, one for Abacavir and Lamivudine and the other for Dolutegravir. But, since analysis of a single sample using two methods instead of one is time and resource consuming and thus expensive, an attempt was made to develop a single and robust method by adopting quality by design (QbD) principles. Design of Experiments (DoE) was applied as a tool to achieve the optimum conditions through Response surface methodology with three method variables, pH, temperature, and mobile phase composition. As the study progressed, it was discovered that establishment of the design space was not viable due to the completely distant pH requirements of the two responses, i.e. (i) retention time for Lamivudine carboxylic acid and (ii) resolution between Abacavir impurity B and unknown impurity. Eventually, neglecting one of these two responses each time, two distinguished design spaces have been established and verified. Edge of failures at both design spaces indicate high probability of failure. It therefore, becomes very important to identify the most robust zone or normal operating range (NOR) within the design space with low risk of failure and high

  20. Occurrence of the antidiabetic drug Metformin and its ultimate transformation product Guanylurea in several compartments of the aquatic cycle.

    Science.gov (United States)

    Trautwein, Christoph; Berset, Jean-Daniel; Wolschke, Hendrik; Kümmerer, Klaus

    2014-09-01

    In 2030, the World Health Organization estimates that more than 350 million people will be diagnosed with diabetes. Consequently, Metformin - the biguanide drug of choice orally administered for diabetes type II - is anticipated to see a spike in production. Unlike many pharmaceutical drugs, Metformin (Met) is not metabolized by humans but passes through the body unchanged. Entering aquatic compartments, such as in sewage, it can be bacterially transformed to the ultimate transformation product Guanylurea (Gua). Sampling over one week (n=5) from a Southern German sewage treatment plant revealed very high average (AV) concentrations in influent (AVMet=111,800ng/L, AVGua=1300ng/L) and effluent samples (AVMet=4800ng/L, AVGua=44,000ng/L). To provide a more complete picture of the distribution and potential persistence of these compounds in the German water cycle, a new, efficient and highly sensitive liquid chromatography mass spectrometric method with direct injection was used for the measurement of Metformin and Guanylurea in drinking, surface, sewage and seawater. Limits of quantification (LOQ) ranging from 2-10ng/L allowed the detection of Metformin and Guanylurea in different locations such as: Lake Constance (n=11: AVMet=102ng/L, AVGua=16ng/L), river Elbe (n=12: AVMet=472ng/L, AVGua=9ng/L), river Weser (n=6: AVMet=349ng/L, AVGua=137ng/L) and for the first time in marine North Sea water (n=14: AVMet=13ng/L, AVGua=11ng/L). Based on daily water discharges, Metformin loads of 15.2kg/d (Elbe) and 6.4kg/d (Weser) into the North Sea were calculated. Lake Constance is used to abstract potable water which is further purified to be used as drinking water. A first screening of two tap water samples contained 2ng/L and 61ng/L of Metformin, respectively. The results of this study suggest that Metformin and Guanylurea could be distributed over a large fraction of the world's potable water sources and oceans. With no natural degradation processes, these compounds can be easily

  1. Trafficking of drug candidates relevant for sports drug testing: detection of non-approved therapeutics categorized as anabolic and gene doping agents in products distributed via the Internet.

    Science.gov (United States)

    Thevis, Mario; Geyer, Hans; Thomas, Andreas; Schänzer, Wilhelm

    2011-05-01

    Identifying the use of non-approved drugs by cheating athletes has been a great challenge for doping control laboratories. This is due to the additional complexities associated with identifying relatively unknown and uncharacterized compounds and their metabolites as opposed to known and well-studied therapeutics. In 2010, the prohibited drug candidates and gene doping substances AICAR and GW1516, together with the selective androgen receptor modulator (SARM) MK-2866 were obtained by the Cologne Doping Control Laboratory from Internet suppliers and their structure, quantity, and formulation elucidated. All three compounds proved authentic as determined by liquid chromatography-high resolution/high accuracy (tandem) mass spectrometry and comparison to reference material. While AICAR was provided as a colourless powder in 100 mg aliquots, GW1516 was obtained as an orange/yellow suspension in water/glycerol (150 mg/ml), and MK-2866 (25 mg/ml) was shipped dissolved in polyethylene glycol (PEG) 300. In all cases, the quantified amounts were considerably lower than indicated on the label. The substances were delivered via courier, with packaging identifying them as containing 'amino acids' and 'green tea extract', arguably to circumvent customs control. Although all of the substances were declared 'for research only', their potential misuse in illicit performance-enhancement cannot be excluded; moreover sports drug testing authorities should be aware of the facile availability of black market copies of these drug candidates. Copyright © 2011 John Wiley & Sons, Ltd.

  2. A proposal for a pharmacokinetic interaction significance classification system (PISCS) based on predicted drug exposure changes and its potential application to alert classifications in product labelling.

    Science.gov (United States)

    Hisaka, Akihiro; Kusama, Makiko; Ohno, Yoshiyuki; Sugiyama, Yuichi; Suzuki, Hiroshi

    2009-01-01

    Pharmacokinetic drug-drug interactions (DDIs) are one of the major causes of adverse events in pharmacotherapy, and systematic prediction of the clinical relevance of DDIs is an issue of significant clinical importance. In a previous study, total exposure changes of many substrate drugs of cytochrome P450 (CYP) 3A4 caused by coadministration of inhibitor drugs were successfully predicted by using in vivo information. In order to exploit these predictions in daily pharmacotherapy, the clinical significance of the pharmacokinetic changes needs to be carefully evaluated. The aim of the present study was to construct a pharmacokinetic interaction significance classification system (PISCS) in which the clinical significance of DDIs was considered with pharmacokinetic changes in a systematic manner. Furthermore, the classifications proposed by PISCS were compared in a detailed manner with current alert classifications in the product labelling or the summary of product characteristics used in Japan, the US and the UK. A matrix table was composed by stratifying two basic parameters of the prediction: the contribution ratio of CYP3A4 to the oral clearance of substrates (CR), and the inhibition ratio of inhibitors (IR). The total exposure increase was estimated for each cell in the table by associating CR and IR values, and the cells were categorized into nine zones according to the magnitude of the exposure increase. Then, correspondences between the DDI significance and the zones were determined for each drug group considering the observed exposure changes and the current classification in the product labelling. Substrate drugs of CYP3A4 selected from three therapeutic groups, i.e. HMG-CoA reductase inhibitors (statins), calcium-channel antagonists/blockers (CCBs) and benzodiazepines (BZPs), were analysed as representative examples. The product labelling descriptions of drugs in Japan, US and UK were obtained from the websites of each regulatory body. Among 220

  3. Kitchen chemistry: A scoping review of the diversionary use of pharmaceuticals for non-medicinal use and home production of drug solutions.

    Science.gov (United States)

    Van Hout, Marie Claire

    2014-01-01

    Misuse of pharmaceuticals is of increasing drug policy and public health concern. A scoping review was conducted on the diversionary use of pharmaceuticals for non-medicinal use and home production of drug solutions. The research question was broad: What is known from the existing literature about the diversion of pharmaceuticals for non-medicinal use and for home production of drug solutions? The scoping process centred on the systematic selection, collection, and summarization of extant knowledge within this broad thematic remit. One hundred and thirty-four records were grouped into discrete thematic categories namely: non medicinal use and tampering with pharmaceuticals, oral misuse of codeine cough syrups, homemade drug solutions, and home-produced drug-related harms in the narrative review design. Forms of abuse of codeine cough syrup include mixtures with alcohol or soft drinks ('Purple Drank'), with kratom leaves ('Kratom cocktails'), or chemically altered to extract dextromorphan ('Lemon Drop'). Production of homemade opiates ('Cheornaya', 'Kolyosa', Himiya', 'Braun', 'Krokodil'), methamphetamine ('Vint', 'Pervitin'), methcathinone ('Jeff'), and cathinone ('Boltushka') are described. Displacement patterns between the non-medical use of pharmaceuticals, commercial, and homemade drugs appear dependent on availability of opiates, prescribing practices, supervision of substitution drug dosing, availability of cheap ingredients, policing, and awareness of harms. Adverse health and social consequences relate to the use of unknown and contaminated (end) substances, injecting practices, redosing, medical complications, and death. The review highlights a public health imperative requiring a multidisciplinary approach to quantify potential impact and required integrated policy responses incorporating international regulation, enforcement, health surveillance and service delivery. Copyright © 2014 John Wiley & Sons, Ltd.

  4. Activities and influence of veterinary drug marketers on antimicrobial usage in livestock production in Oyo and Kaduna States, Nigeria

    Directory of Open Access Journals (Sweden)

    Olufemi Ernest Ojo

    2017-09-01

    Full Text Available Antimicrobial usage in animals contributes to the emergence of antimicrobial resistant bacterial strains. Investigations were carried out on how the characteristics, knowledge, attitude and practices of antimicrobial marketers influenced antimicrobials usage in animal production in Oyo and Kaduna States, Nigeria. Focus group discussions, in-depth interviews and structured questionnaires were used to gather information about the characteristics and activities of antimicrobial marketers. Overall, 70 (56.9 % of 123 marketers had post-secondary education while 76 (61.8 % were trained on the use of antimicrobials. Eighteen (14.6 % of the marketers were licensed veterinarians. Only 51 (41.5 % marketers displayed adequate knowledge about antimicrobials and antimicrobial usage. Sixty-seven (54.6 % marketers requested a prescription before selling antimicrobials while 113 (91.9 % marketer recommended antimicrobials for use in animals. Two-third of the marketers (66.7 % prescribed antimicrobials without physically examining sick animals but based their prescriptions on verbal reports of clinical signs by farmers and on their personal experience. Marketers with higher educational qualification displayed more adequate knowledge of antimicrobials and antimicrobial usage than those with basic education background only. More years of experience in antimicrobial marketing did not translate to better knowledge on antimicrobial usage. Only 45 (36.6 % respondents were aware of the existence of regulatory agencies monitoring the use of antimicrobials in animals. Farmers ignored the services of veterinarians in the diagnosis and control of animal diseases but resorted to drug marketers for help. Effective communication of existing legislations on antimicrobial usage, improved access to veterinary services and strict enforcement of regulatory policies are recommended for checking non-judicious use of antimicrobial agents in animal production. Sales of

  5. Animal products, diseases and drugs: a plea for better integration between agricultural sciences, human nutrition and human pharmacology

    Directory of Open Access Journals (Sweden)

    Haug Anna

    2011-01-01

    Full Text Available Abstract Eicosanoids are major players in the pathogenesis of several common diseases, with either overproduction or imbalance (e.g. between thromboxanes and prostacyclins often leading to worsening of disease symptoms. Both the total rate of eicosanoid production and the balance between eicosanoids with opposite effects are strongly dependent on dietary factors, such as the daily intakes of various eicosanoid precursor fatty acids, and also on the intakes of several antioxidant nutrients including selenium and sulphur amino acids. Even though the underlying biochemical mechanisms have been thoroughly studied for more than 30 years, neither the agricultural sector nor medical practitioners have shown much interest in making practical use of the abundant high-quality research data now available. In this article, we discuss some specific examples of the interactions between diet and drugs in the pathogenesis and therapy of various common diseases. We also discuss, using common pain conditions and cancer as specific examples, how a better integration between agricultural science, nutrition and pharmacology could lead to improved treatment for important diseases (with improved overall therapeutic effect at the same time as negative side effects and therapy costs can be strongly reduced. It is shown how an unnaturally high omega-6/omega-3 fatty acid concentration ratio in meat, offal and eggs (because the omega-6/omega-3 ratio of the animal diet is unnaturally high directly leads to exacerbation of pain conditions, cardiovascular disease and probably most cancers. It should be technologically easy and fairly inexpensive to produce poultry and pork meat with much more long-chain omega-3 fatty acids and less arachidonic acid than now, at the same time as they could also have a similar selenium concentration as is common in marine fish. The health economic benefits of such products for society as a whole must be expected vastly to outweigh the direct

  6. [Orphan drugs].

    Science.gov (United States)

    Golocorbin Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojsa; Mikov, Momir

    2013-01-01

    Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in "adopting" them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. THE BEGINNING OF ORPHAN DRUGS DEVELOPMENT: This problem was first recognized by Congress of the United States of America in January 1983, and when the "Orphan Drug Act" was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs.

  7. ASM Inaugural Lecture 2010: Single crystal X-ray structural determination: A powerful technique for natural products research and drug discovery

    International Nuclear Information System (INIS)

    Fun Hoong Kun; Chantrapromma, S.; Boonnak, N.; Lee, V.S.

    2010-01-01

    Drug discovery from natural products resources have been extensively studied worldwide because natural products with their great structural diversity have traditionally provided most of the drugs in use. They offer major opportunities for finding novel low molecular weight leading-structures that are active against a wide range of assay targets. The most important step in the discovery process is the identification of compounds with interesting biological activity. Single crystal X-ray structure determination is a powerful technique for natural products research and drug discovery. The detailed three-dimensional structures that emerge can be co-related to the activities to these structures. In this article the following is presented: (i) co-crystal and disorder structures; (ii) determination of absolute configuration and (iii) the ability to distinguish between whether a natural product compound is a natural product or a natural product artifact. All these three properties are unique to the technique of single crystal X-ray structure determination. Case (iii) was demonstrated with a compound containing a chromene ring, namely macluraxanthone (which was isolated from Cratoxylum formosum subsp. pruniflorum, a Thai medicinal plant). (author)

  8. How Deformation Behavior Controls Product Performance After Twin Screw Granulation With High Drug Loads and Crospovidone as Disintegrant.

    Science.gov (United States)

    Meier, Robin; Moll, Klaus-Peter; Krumme, Markus; Kleinebudde, Peter

    2017-01-01

    This study addresses the quantitative influence of 12 different materials (active pharmaceutical ingredients and excipients as surrogate active pharmaceutical ingredients) on the critical quality attributes of twin screw granulated products and subsequently produced tablets. Prestudies demonstrated the significant influence of the chosen model materials (in combination with crospovidone) on the disintegration behavior of the resulting tablets, despite comparable tablet porosities. This study elucidates possible reasons for the varying disintegration behavior by investigating raw material, granule, and tablet properties. An answer could be found in the mechanical properties of the raw materials and the produced granules. Through compressibility studies, the materials could be classified into materials with high compressibility, which deform rather plastically under compression stress, and low compressibility, which display breakages under compression stress. In general, and apart from (pseudo)-polymorphic transformations, brittle materials featured excellent disintegration performance, even at low resulting tablet porosities plastically deformable materials mostly did not reveal any disintegration. These findings must be considered in the development of simplified formulations with high drug loads, in which the active pharmaceutical ingredient predominantly defines the deformation behavior of the granule. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  9. Scientific perspectives on extending the provision for waivers of in vivo bioavailability and bioequivalence studies for drug products containing high solubility-low permeability drugs (BCS-Class 3).

    Science.gov (United States)

    Stavchansky, Salomon

    2008-06-01

    Recently, there has been increased interest in extending the provision for waivers of in vivo bioavailability and bioequivalence (BA-BE) studies that appeared in the guidance published by the Food and Drug Administration (FDA) (1) to pharmaceutical products containing Class 3 drugs (High solubility-Low Permeability). The extension of the Biopharmaceutics Classification System (BCS) to Class 3 drugs is meritorious because of its impact on public health policy considerations. The rate limiting step in the absorption of Class 3 drugs is the permeability through the intestinal membrane. This commentary will focus its attention on the scientific considerations which need to be examined to assess the risk and the benefit prior to granting a waiver of in vivo bioavailability and/or bioequivalence studies for Class 3 drugs. It will examine the forces affecting the interconnectivity of the neuronal, immunological and hormonal systems in the gastrointestinal tract that may affect its permeability and functionality. It will also challenge the assumption that in vitro dissolution and in vitro permeability studies in tissue cultures in the presence and absence of excipients are good predictors for in vivo dissolution and in vivo permeability which are at the heart of the BCS.

  10. Side-stream products of edible oil refining as feedstocks in biodiesel production

    Directory of Open Access Journals (Sweden)

    Cvetković Bojan S.

    2016-01-01

    Full Text Available Biodiesel, a diesel fuel alternative, is produced from vegetable oils and animal fats by the transesterification reaction of triacylglycerols and lower aliphatic alcohols. Beside number advantages related to fossil fuels, the main barrier to biodiesel wider commercial use is the high price of edible oils. Recently, the special attention was given to side-stream products of edible oil refining as low-cost triacylglycerol sources for biodiesel production because of their positive economic and ecological effects. In this paper, the different procedures for biodiesel production from side-stream refining products such as soapstock, spent bleaching earth and deodorizer distillate were analyzed. The main goal of this paper is to analyze the possibilities for reusing the by-products of edible oil refinement in the biodiesel production.

  11. A unique drug distribution process for radium Ra 223 dichloride injection and its implication for product quality, patient privacy, and delineation of professional responsibilities.

    Science.gov (United States)

    Dansereau, Raymond N

    2014-11-01

    On May 15, 2013, Bayer Healthcare Pharmaceuticals announced that it had received marketing approval for the therapeutic radioactive medication radium Ra 223 dichloride injection (Xofigo; Ra 223). The product acquisition and distribution process for hospital-based nuclear pharmacies and nuclear medicine services is unlike any other. The product is distributed as a low-risk compounded sterile preparation through a single compounding nuclear pharmacy located in Denver, Colorado, pursuant to a prescription. This model for drug distribution and delivery to the user institution has implications for product quality, patient privacy, and delineation of professional responsibilities. © The Author(s) 2014.

  12. A QRM Discussion of Microbial Contamination of Non-sterile Drug Products, Using FDA and EMA Warning Letters Recorded between 2008 and 2016.

    Science.gov (United States)

    Santos, Ana M C; Doria, Mara S; Meirinhos-Soares, Luís; Almeida, António J; Menezes, José C

    2018-01-01

    Microbial quality control of non-sterile drug products has been a concern to regulatory agencies and the pharmaceutical industry since the 1960s. Despite being an old challenge to companies, microbial contamination still affects a high number of manufacturers of non-sterile products. Consequences go well beyond the obvious direct costs related to batch rejections or product recalls, as human lives and a company's reputation are significantly impacted if such events occur. To better manage risk and establish effective mitigation strategies, it is necessary to understand the microbial hazards involved in non-sterile drug products manufacturing, be able to evaluate their potential impact on final product quality, and apply mitigation actions. Herein we discuss the most likely root causes involved in microbial contaminations referenced in warning letters issued by US health authorities and non-compliance reports issued by European health authorities over a period of several years. The quality risk management tools proposed were applied to the data gathered from those databases, and a generic risk ranking was provided based on a panel of non-sterile drug product manufacturers that was assembled and given the opportunity to perform the risk assessments. That panel identified gaps and defined potential mitigation actions, based on their own experience of potential risks expected for their processes. Major findings clearly indicate that the manufacturers affected by the warning letters should focus their attention on process improvements and microbial control strategies, especially those related to microbial analysis and raw material quality control. Additionally, the WLs considered frequently referred to failures in quality-related issues, which indicates that the quality commitment should be reinforced at most companies to avoid microbiological contaminations. LAY ABSTRACT: Microbial contamination of drug products affects the quality of non-sterile drug products produced

  13. Study on the thermal degradation of 3-MCPD esters in model systems simulating deodorization of vegetable oils.

    Science.gov (United States)

    Ermacora, Alessia; Hrncirik, Karel

    2014-05-01

    The establishment of effective strategies for the mitigation of 3-MCPD esters in refined vegetable oils is restricted by limited knowledge of their mechanisms of formation and decomposition. In order to gain better understanding on the thermal stability of these compounds, a model system for mimicking oil refining conditions was developed. Pure 3-MCPD esters (3-MCPD dipalmitate and 3-MCPD dilaurate) were subjected to thermal treatment (180-260°C) and the degradation products where monitored over time (0-24h). After 24h of treatment, both 3-MCPD esters showed a significant degradation (ranging from 30% to 70%), correlating with the temperature applied. The degradation pathway, similar for both compounds, was found to involve isomerisation (very rapid, equilibrium was reached within 2h at 260°C), dechlorination and deacylation reactions. The higher relative abundance of non-chlorinated compounds, namely acylglycerols, in the first stages of the treatment suggested that dechlorination is preferred over deacylation with the conditions applied in this study. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. The Development and Validation of an In Vitro Airway Model to Assess Realistic Airway Deposition and Drug Permeation Behavior of Orally Inhaled Products Across Synthetic Membranes.

    Science.gov (United States)

    Huynh, Bao K; Traini, Daniela; Farkas, Dale R; Longest, P Worth; Hindle, Michael; Young, Paul M

    2018-04-01

    Current in vitro approaches to assess lung deposition, dissolution, and cellular transport behavior of orally inhaled products (OIPs) have relied on compendial impactors to collect drug particles that are likely to deposit in the airway; however, the main drawback with this approach is that these impactors do not reflect the airway and may not necessarily represent drug deposition behavior in vivo. The aim of this article is to describe the development and method validation of a novel hybrid in vitro approach to assess drug deposition and permeation behavior in a more representative airway model. The medium-sized Virginia Commonwealth University (VCU) mouth-throat (MT) and tracheal-bronchial (TB) realistic upper airway models were used in this study as representative models of the upper airway. The TB model was modified to accommodate two Snapwell ® inserts above the first TB airway bifurcation region to collect deposited nebulized ciprofloxacin-hydrochloride (CIP-HCL) droplets as a model drug aerosol system. Permeation characteristics of deposited nebulized CIP-HCL droplets were assessed across different synthetic membranes using the Snapwell test system. The Snapwell test system demonstrated reproducible and discriminatory drug permeation profiles for already dissolved and nebulized CIP-HCL droplets through a range of synthetic permeable membranes under different test conditions. The rate and extent of drug permeation depended on the permeable membrane material used, presence of a stirrer in the receptor compartment, and, most importantly, the drug collection method. This novel hybrid in vitro approach, which incorporates a modified version of a realistic upper airway model, coupled with the Snapwell test system holds great potential to evaluate postairway deposition characteristics, such as drug permeation and particle dissolution behavior of OIPs. Future studies will expand this approach using a cell culture-based setup instead of synthetic membranes, within a

  15. 21 CFR 310.545 - Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses.

    Science.gov (United States)

    2010-04-01

    ..., powdered extract Betaine hydrochloride Bismuth subcarbonate Bismuth subgallate Black radish powder Blessed... Pineapple enzymes Plantago seed Potassium citrate Pyridoxine hydrochloride (vitamin B6) Riboflavin Rice... the Federal Food, Drug, and Cosmetic Act (the Act), for which an approved new drug application under...

  16. 76 FR 25696 - Guidance for Industry on Dosage Delivery Devices for Orally Ingested OTC Liquid Drug Products...

    Science.gov (United States)

    2011-05-05

    ... are manufacturing, marketing, or distributing orally ingested over-the-counter (OTC) liquid drug... overdoses that can result from the use of dosage delivery devices with markings that are inconsistent or... because of ongoing concerns about potentially serious accidental drug overdoses that can result from the...

  17. An analysis of psychotropic drug sales. Increasing sales of selective serotonin reuptake inhibitors anre closely related to number of products

    DEFF Research Database (Denmark)

    Nielsen, Margrethe; Gøtzsche, Peter C.

    2011-01-01

    used data from various sources to establish the sales curves of psychotropic drugs in the period 1970 to 2007, based on the Anatomic Therapeutic Classification system and Defined Daily Doses. RESULTS: Fluctuations in sales of psychotropic drugs that cannot be explained by disease prevalence were caused...

  18. 78 FR 72901 - Draft Guidance; Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal...

    Science.gov (United States)

    2013-12-04

    ... provisions of the FD&C Act remain in effect for compounded drugs, however, even if the conditions in section 503A are met. The conditions of section 503A of the FD&C Act included restrictions on the advertising... the Drug Quality and Security Act to remove the unconstitutional advertising, promotion, and...

  19. Detailed sorption characteristics of the anti-diabetic drug metformin and its transformation product guanylurea in agricultural soils.

    Science.gov (United States)

    Briones, Rowena M; Sarmah, Ajit K

    2018-07-15

    Detection of metformin, an antidiabetic drug and its transformation product guanylurea in various environmental matrices such as surface water and groundwater, coupled with their effects on aquatic organisms warrant an understanding of the compounds fate and behaviour in the environment. Batch studies were conducted with the aim of evaluating the sorption of these two emerging contaminants in six New Zealand agricultural soils of contrasting physico-chemical properties. Kinetic studies revealed that metformin and guanylurea sorption in Te Kowhai soil was very rapid initially achieving 90% sorption within the first 4 and 13h, respectively. Fit of several isotherm models to the measured batch sorption data showed that the hybrid models Langmuir-Freundlich and Redlich-Peterson best described the isotherms. Freundlich isotherm showed higher linearity for guanylurea (n F =0.58-0.93) in all soils compared to metformin (n F =0.25-0.71). A linear isotherm was fitted at environmentally relevant low concentrations (< 3mg/L) of target compounds and calculated values of sorption distribution coefficient (K d ) were in the range of 8.97 to 53.49L/kg for metformin and between 10.6 and 37.51L/kg for guanylurea. Sorption of both metformin and guanylurea was dependent on the soil characteristics, however, no generalisation could be made as to which had higher affinity to soils studied. Pearson's correlation and multiple regression analyses indicate that Si/Al (p=0.042) and clay (p=0.015) significantly influenced metformin K d values, whereas the soil's cation exchange capacity (p=0.024) is the single most significant factor determining guanylurea sorption in soils. It is likely that the type of minerals present in soils and its ion-exchange capacity could play an important role in metformin and guanylurea sorption, respectively. Copyright © 2018. Published by Elsevier B.V.

  20. Purity assessment of recombinant human granulocyte colony-stimulating factor in finished drug product by capillary zone electrophoresis.

    Science.gov (United States)

    Benković, Goran; Skrlin, Ana; Madić, Tomislav; Debeljak, Zeljko; Medić-Šarić, Marica

    2014-09-01

    Current methods for determination of impurities with different charge-to-volume ratio are limited especially in terms of sensitivity and precision. The main goal of this research was to establish a quantitative method for determination of impurities with charges differing from that of recombinant human granulocyte colony-stimulating factor (rhG-CSF, filgrastim) with superior precision and sensitivity compared to existing methods. A CZE method has been developed, optimized, and validated for a purity assessment of filgrastim in liquid pharmaceutical formulations. Optimal separation of filgrastim from the related impurities with different charges was achieved on a 50 μm id fused-silica capillary of a total length of 80.5 cm. A BGE that contains 100 mM phosphoric acid adjusted to pH 7.0 with triethanolamine was used. The applied voltage was 20 kV while the temperature was maintained at 25°C. UV detection was set to 200 nm. Method was validated in terms of selectivity/specificity, linearity, precision, LOD, LOQ, stability, and robustness. Linearity was observed in the concentration range of 6-600 μg/mL and the LOQ was determined to be 0.3% relative to the concentration of filgrastim of 0.6 mg/mL. Other validation parameters were also found to be acceptable; thus the method was successfully applied for a quantitative purity assessment of filgrastim in a finished drug product. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  2. Failures to further developing orphan medicinal products after designation granted in Europe: an analysis of marketing authorisation failures and abandoned drugs.

    Science.gov (United States)

    Giannuzzi, Viviana; Landi, Annalisa; Bosone, Enrico; Giannuzzi, Floriana; Nicotri, Stefano; Torrent-Farnell, Josep; Bonifazi, Fedele; Felisi, Mariagrazia; Bonifazi, Donato; Ceci, Adriana

    2017-09-11

    The research and development process in the field of rare diseases is characterised by many well-known difficulties, and a large percentage of orphan medicinal products do not reach the marketing approval.This work aims at identifying orphan medicinal products that failed the developmental process and investigating reasons for and possible factors influencing failures. Drugs designated in Europe under Regulation (European Commission) 141/2000 in the period 2000-2012 were investigated in terms of the following failures: (1) marketing authorisation failures (refused or withdrawn) and (2) drugs abandoned by sponsors during development.Possible risk factors for failure were analysed using statistically validated methods. This study points out that 437 out of 788 designations are still under development, while 219 failed the developmental process. Among the latter, 34 failed the marketing authorisation process and 185 were abandoned during the developmental process. In the first group of drugs (marketing authorisation failures), 50% reached phase II, 47% reached phase III and 3% reached phase I, while in the second group (abandoned drugs), the majority of orphan medicinal products apparently never started the development process, since no data on 48.1% of them were published and the 3.2% did not progress beyond the non-clinical stage.The reasons for failures of marketing authorisation were: efficacy/safety issues (26), insufficient data (12), quality issues (7), regulatory issues on trials (4) and commercial reasons (1). The main causes for abandoned drugs were efficacy/safety issues (reported in 54 cases), inactive companies (25.4%), change of company strategy (8.1%) and drug competition (10.8%). No information concerning reasons for failure was available for 23.2% of the analysed products. This analysis shows that failures occurred in 27.8% of all designations granted in Europe, the main reasons being safety and efficacy issues. Moreover, the stage of development

  3. Integrated Application of Quality-by-Design Principles to Drug Product Development: A Case Study of Brivanib Alaninate Film-Coated Tablets.

    Science.gov (United States)

    Badawy, Sherif I F; Narang, Ajit S; LaMarche, Keirnan R; Subramanian, Ganeshkumar A; Varia, Sailesh A; Lin, Judy; Stevens, Tim; Shah, Pankaj A

    2016-01-01

    Modern drug product development is expected to follow quality-by-design (QbD) paradigm. At the same time, although there are several issue-specific examples in the literature that demonstrate the application of QbD principles, a holistic demonstration of the application of QbD principles to drug product development and control strategy, is lacking. This article provides an integrated case study on the systematic application of QbD to product development and demonstrates the implementation of QbD concepts in the different aspects of product and process design for brivanib alaninate film-coated tablets. Using a risk-based approach, the strategy for development entailed identification of product critical quality attributes (CQAs), assessment of risks to the CQAs, and performing experiments to understand and mitigate identified risks. Quality risk assessments and design of experiments were performed to understand the quality of the input raw materials required for a robust formulation and the impact of manufacturing process parameters on CQAs. In addition to the material property and process parameter controls, the proposed control strategy includes use of process analytical technology and conventional analytical tests to control in-process material attributes and ensure quality of the final product. Copyright © 2016. Published by Elsevier Inc.

  4. Drugs@FDA Database

    Data.gov (United States)

    U.S. Department of Health & Human Services — Information about FDA-approved brand name and generic prescription and over-the-counter human drugs and biological therapeutic products. Drugs@FDA includes most of...

  5. CMS Drug Spending

    Data.gov (United States)

    U.S. Department of Health & Human Services — CMS has released several information products that provide spending information for prescription drugs in the Medicare and Medicaid programs. The CMS Drug Spending...

  6. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers.

    Science.gov (United States)

    Lin, Chih-Hung; Chen, Chun-Han; Lin, Zih-Chan; Fang, Jia-You

    2017-04-01

    Chemical and enzymatic barriers in the gastrointestinal (GI) tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs) are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs. Copyright © 2017. Published by Elsevier B.V.

  7. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers

    Directory of Open Access Journals (Sweden)

    Chih-Hung Lin

    2017-04-01

    Full Text Available Chemical and enzymatic barriers in the gastrointestinal (GI tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs.

  8. 21 CFR 310.544 - Drug products containing active ingredients offered over-the-counter (OTC) for use as a smoking...

    Science.gov (United States)

    2010-04-01

    ... offered over-the-counter (OTC) for use as a smoking deterrent. 310.544 Section 310.544 Food and Drugs FOOD... ingredients offered over-the-counter (OTC) for use as a smoking deterrent. (a) Any product that bears labeling claims that it “helps stop or reduce the cigarette urge,” “helps break the cigarette habit,” “helps stop...

  9. Ability to join the workforce and work productivity among drug users under methadone maintenance treatment in a mountainous area of Northern Vietnam: a cross-sectional study.

    Science.gov (United States)

    Nong, Vuong Minh; Boggiano, Victoria L; Nguyen, Lan Huong Thi; Nguyen, Cuong Tat; Nguyen, Long Hoang; Xuan Bach, Tran; Nguyen, Hung Van; Hoang, Canh Dinh; Latkin, Carl A; Vu, Minh Thuc Thi

    2017-07-26

    A major measure of treatment success for drug users undergoing rehabilitation is the ability to enter the workforce and generate income. This study examines the absenteeism and productivity among people who inject drugs (PWID) enrolled in methadone maintenance treatment (MMT) in Northern Vietnam. We conducted a cross-sectional study in two clinics in Tuyen Quang province. A total of 241 patients enrolled in MMT. Patients' work productivity was measured using the WPAI-GH instrument (Work Productivity and Activity Impairment Questionnaire: General Health V2.0). We also collected additional characteristics about participants' employment history, such as proficient jobs, whether they actively found a new job and be accepted by employers. Most of the participants (>90%) were employed at the time of the study. Rates of absenteeism (missed work), presenteeism (impairment while working) and overall loss of productivity were 15.8%, 5.6% and 11.2%, respectively, as measured by the WPAI-GH questionnaire. The most proficient job was 'freelancer' (17.5%), followed by 'blue-collar worker' (10.6%) and 'farmer' (10.2%). Only 26.8% of patients reported that they actively sought jobs in the past. About half of them had been refused by employers because of their drug use history and/or HIV status. We found no statistically significant difference between patients enrolled in MMT for 1 year. Factors associated with higher work productivity included not endorsing problems in mobility, self-care or pain; being HIV-negative and having greater MMT treatment adherence. Our study highlights the high employment rate and work productivity among PWID in MMT programmes in remote areas of Northern Vietnam. The results can help to improve the quality and structure of MMT programmes across Vietnam and in other countries. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise

  10. Ability to join the workforce and work productivity among drug users under methadone maintenance treatment in a mountainous area of Northern Vietnam: a cross-sectional study

    Science.gov (United States)

    Nong, Vuong Minh; Boggiano, Victoria L; Nguyen, Lan Huong Thi; Nguyen, Cuong Tat; Nguyen, Long Hoang; Xuan Bach, Tran; Nguyen, Hung Van; Hoang, Canh Dinh; Latkin, Carl A; Vu, Minh Thuc Thi

    2017-01-01

    Objectives A major measure of treatment success for drug users undergoing rehabilitation is the ability to enter the workforce and generate income. This study examines the absenteeism and productivity among people who inject drugs (PWID) enrolled in methadone maintenance treatment (MMT) in Northern Vietnam. Setting We conducted a cross-sectional study in two clinics in Tuyen Quang province. Participants A total of 241 patients enrolled in MMT. Primary and secondary outcome measures Patients’ work productivity was measured using the WPAI-GH instrument (Work Productivity and Activity Impairment Questionnaire: General Health V2.0). We also collected additional characteristics about participants’ employment history, such as proficient jobs, whether they actively found a new job and be accepted by employers. Results Most of the participants (>90%) were employed at the time of the study. Rates of absenteeism (missed work), presenteeism (impairment while working) and overall loss of productivity were 15.8%, 5.6% and 11.2%, respectively, as measured by the WPAI-GH questionnaire. The most proficient job was ‘freelancer’ (17.5%), followed by ‘blue-collar worker’ (10.6%) and ‘farmer’ (10.2%). Only 26.8% of patients reported that they actively sought jobs in the past. About half of them had been refused by employers because of their drug use history and/or HIV status. We found no statistically significant difference between patients enrolled in MMT for 1 year. Factors associated with higher work productivity included not endorsing problems in mobility, self-care or pain; being HIV-negative and having greater MMT treatment adherence. Conclusion Our study highlights the high employment rate and work productivity among PWID in MMT programmes in remote areas of Northern Vietnam. The results can help to improve the quality and structure of MMT programmes across Vietnam and in other countries. PMID:28751487

  11. Physico-chemical Stability of MabThera Drug-product Solution for Subcutaneous Injection under in-use Conditions with Different Administration Materials.

    Science.gov (United States)

    Mueller, Claudia; Dietel, Elke; Heynen, Severin R; Nalenz, Heiko; Goldbach, Pierre; Mahler, Hanns-Christian; Schmidt, Johannes; Grauschopf, Ulla; Schoenhamnmer, Karin

    2015-01-01

    MabThera is an essential component of the standard-of-care regimens in the treatment of non-Hodgkin lymphoma and Chronic Lymphatic Leukemia. MabThera for subcutaneous injection is a novel line extension that has been approved by the European Medicines Agency for the treatment of patients with follicular lymphoma and diffuse large B-cell lymphoma. This study aimed to evaluate in-use stability data of MabThera subcutaneous drug-product solution in single-use syringes for subcutaneous administration according to the European Medicines Agency guideline. The drug-product solution was exposed to material contact surfaces of five different administration setups commonly used in subcutaneous drug delivery. MabThera subcutaneous was transferred under aseptic conditions into polypropylene and polycarbonate syringes and stored for 1, 2, and 4 weeks at 2°C to 8°C followed by 24 hours at 30°C. After storage, subcutaneous administration was simulated and MabThera subcutaneous drug-product solution quality attributes were evaluated by using compendial physico-chemical tests, as well as suitable and validated molecule- and formulation-specific analytical methods. MabThera subcutaneous vials were treated and analyzed in parallel. The physico-chemical results of MabThera subcutaneous in the different setups were comparable to the control for all timepoints. No change in drug-product quality after storage and simulated administration was found compared to the control. However, since single-dose products do not contain preservatives, microbial contamination and growth needs to be avoided and product sterility needs to be ensured. The results showed that MabThera subcutaneous remains compatible and stable, from a physico-chemical perspective, for up to 4 weeks at 2°C to 8°C followed by 24 hours at 30°C with the contact materials tested in this study. In order to avoid and minimize microbial growth, MabThera subcutaneous should be used immediately after removal from the original

  12. Utilization of oleo-chemical industry by-products for biosurfactant production

    Science.gov (United States)

    2013-01-01

    Biosurfactants are the surface active compounds produced by micro-organisms. The eco-friendly and biodegradable nature of biosurfactants makes their usage more advantageous over chemical surfactants. Biosurfactants encompass the properties of dropping surface tension, stabilizing emulsions, promoting foaming and are usually non- toxic and biodegradable. Biosurfactants offer advantages over their synthetic counterparts in many applications ranging from environmental, food, and biomedical, cosmetic and pharmaceutical industries. The important environmental applications of biosurfactants include bioremediation and dispersion of oil spills, enhanced oil recovery and transfer of crude oil. The emphasis of present review shall be with reference to the commercial production, current developments and future perspectives of a variety of approaches of biosurfactant production from the micro-organisms isolated from various oil- contaminated sites and from the by-products of oleo-chemical industry wastes/ by-products viz. used edible oil, industrial residues, acid oil, deodorizer distillate, soap-stock etc. PMID:24262384

  13. Labelled drug-related public expenditure in relation to gross domestic product (GDP) in Europe: a luxury good?

    LENUS (Irish Health Repository)

    Prieto, Luis

    2010-01-01

    "Labelled drug-related public expenditure" is the direct expenditure explicitly labelled as related to illicit drugs by the general government of the state. As part of the reporting exercise corresponding to 2005, the European Monitoring Centre for Drugs and Drug Addiction\\'s network of national focal points set up in the 27 European Union (EU) Member States, Norway, and the candidates countries to the EU, were requested to identify labelled drug-related public expenditure, at the country level. This was reported by 10 countries categorised according to the functions of government, amounting to a total of EUR 2.17 billion. Overall, the highest proportion of this total came within the government functions of Health (66%), and Public Order and Safety (POS) (20%). By country, the average share of GDP was 0.023% for Health, and 0.013% for POS. However, these shares varied considerably across countries, ranging from 0.00033% in Slovakia, up to 0.053% of GDP in Ireland in the case of Health, and from 0.003% in Portugal, to 0.02% in the UK, in the case of POS; almost a 161-fold difference between the highest and the lowest countries for Health, and a 6-fold difference for POS. Why do Ireland and the UK spend so much in Health and POS, or Slovakia and Portugal so little, in GDP terms? To respond to this question and to make a comprehensive assessment of drug-related public expenditure across countries, this study compared Health and POS spending and GDP in the 10 reporting countries. Results found suggest GDP to be a major determinant of the Health and POS drug-related public expenditures of a country. Labelled drug-related public expenditure showed a positive association with the GDP across the countries considered: r = 0.81 in the case of Health, and r = 0.91 for POS. The percentage change in Health and POS expenditures due to a one percent increase in GDP (the income elasticity of demand) was estimated to be 1.78% and 1.23% respectively. Being highly income elastic

  14. Deodorant bacteria; Des bacteries desodorisantes

    Energy Technology Data Exchange (ETDEWEB)

    Fanlo, J.L. [Ecole Nationale Superieure des Mines, 30 - Ales (France)

    1998-02-01

    Purifying bacteria: if this concept is not new, its application to gases cleansing has only been developed recently. This method allows to eliminate the volatile organic compounds and the gaseous effluents odors which come from industrial sites. Three bioreactors types exist at the present time. Their principles are explained. (O.M.) 6 refs.

  15. Drug Facts

    Medline Plus

    Full Text Available ... Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use and Other People Drug Use and Families Drug Use and Kids Drug Use and Unborn ...

  16. Drug Facts

    Medline Plus

    Full Text Available ... Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, ... Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug Use and Kids ...

  17. Drug Facts

    Medline Plus

    Full Text Available ... People Drug Use and Families Drug Use and Kids Drug Use and Unborn Children Drug Use and ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used ...

  18. Surviving the housing crisis: Social violence and the production of evictions among women who use drugs in Vancouver, Canada.

    Science.gov (United States)

    Collins, Alexandra B; Boyd, Jade; Damon, Will; Czechaczek, Sandra; Krüsi, Andrea; Cooper, Hannah; McNeil, Ryan

    2018-04-11

    Single room accommodation (SRA) housing is among the only forms of accessible housing to marginalized women who use illicit drugs in many urban settings. However, SRA housing environments may create specific health and drug risks for women. Little research has examined the gendered mechanisms contributing to housing vulnerability for women who use drugs and the subsequent ways they aim to mitigate harm. This study examines the gendered vulnerabilities to, and harms stemming from, evictions from SRAs in Vancouver, Canada. Qualitative interviews were conducted with 56 people who use drugs who were recently evicted (past 60 days) from SRAs in Vancouver's Downtown Eastside neighbourhood, 19 of whom identified as women which informed this analysis. Participants were recruited by Peer Researcher Assistants for baseline and follow-up interviews three to six months later. Interview transcripts were analyzed thematically and interpreted by drawing on concepts of social violence. Findings underscore how gendered violence and forms of social control operationalized within SRAs normalized violence against women and restricted their agency. Surveillance mechanisms increased women's experiences of violence as they sought to evade such interventions. Post-eviction, women faced pronounced vulnerability to harm which reinforced their social and spatial marginality within a drug scene. Collectively, women's experiences within SRAs highlight how the hybrid forms of disciplinary mechanisms used within these housing environments significantly impacted women's experiences of harm. Greater attention to the impacts of housing and building policies on women who use drugs is needed to better address the morbidity and mortality of this population. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Usefulness of radiatively obtained acrylamide polymers for production of drug forms with controlled release of the therapeutic component

    International Nuclear Information System (INIS)

    Mosiniak, T.; Switek, W.

    1988-01-01

    Using 60 Co gamma radiation as a factor initiating polymerization and cross-linking of polymers, polyacrylamide matrices were formed with the following therapeutic agents: aspirin, amidopyrin, sodium salicylate. Gamma radiation doses ranged from 3.5 to 22.5 kGy, dose rate was 0.138 Gy x s -1 . Kinetics of the therapeutic agent release from the matrix polymers was determined by measurement of per cent of the drug release in the course of time and calculations of release rate constants. The preparations containing slowly released drugs were obtained. 12 figs., 2 tabs., 11 refs. (author)

  20. Discrepancies in listed adverse drug reactions in pharmaceutical product information supplied by the regulatory authorities in Denmark and the USA

    DEFF Research Database (Denmark)

    Eriksson, Robert; Aagaard, Lise; Jensen, Lars Juhl

    2014-01-01

    as ADRs listed only in one country or listed with different frequencies. We analyzed PIs for 40 separate drugs from ten therapeutic groups and assigned the 4003 identified ADRs to System Organ Classes (Medical Dictionary for Regulatory Activities [MedDRA] terminology). Less than half of listed ADRs (n...

  1. 75 FR 11549 - Determination That PRO-BANTHINE (Propantheline Bromide) Tablets and 14 Other Drug Products Were...

    Science.gov (United States)

    2010-03-11

    ... marketing for reasons other than safety or effectiveness. Approved ANDAs that refer to the NDAs listed in... From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION... in this document were not withdrawn from sale for reasons of safety or effectiveness. This...

  2. 77 FR 27591 - Labeling and Effectiveness Testing; Sunscreen Drug Products for Over-the-Counter Human Use; Delay...

    Science.gov (United States)

    2012-05-11

    ... and Drug Administration, HHS. ACTION: Final rule; delay of compliance dates; request for comments... that FDA has delayed implementation of rules in the past when a delay is justified. We acknowledge that... implementing the delay of the compliance dates for the 2011 final rule. In accordance with Sec. 10.40(e)(1...

  3. 21 CFR 201.56 - Requirements on content and format of labeling for human prescription drug and biological products.

    Science.gov (United States)

    2010-04-01

    ... evidence of effectiveness. Conclusions based on animal data but necessary for safe and effective use of the....3 Nursing mothers 8.4 Pediatric use 8.5 Geriatric use 9 Drug Abuse and Dependence 9.1 Controlled substance 9.2 Abuse 9.3 Dependence 10 Overdosage 11 Description 12 Clinical Pharmacology 12.1 Mechanism of...

  4. 21 CFR 201.326 - Over-the-counter drug products containing internal analgesic/antipyretic active ingredients...

    Science.gov (United States)

    2010-04-01

    ... higher if you [bullet] are age 60 or older [bullet] have had stomach ulcers or bleeding problems [bullet... stomach ulcers or bleeding problems [bullet] takes a blood thinning (anticoagulant) or steroid drug... bleeding. The chance is higher if the user [bullet] has had stomach ulcers or bleeding problems [bullet...

  5. Protein structure similarity clustering (PSSC) and natural product structure as inspiration sources for drug development and chemical genomics

    NARCIS (Netherlands)

    Dekker, Frank J; Koch, Marcus A; Waldmann, Herbert; Dekker, Frans

    Finding small molecules that modulate protein function is of primary importance in drug development and in the emerging field of chemical genomics. To facilitate the identification of such molecules, we developed a novel strategy making use of structural conservatism found in protein domain

  6. On-line coupling of size exclusion chromatography with mixed-mode liquid chromatography for comprehensive profiling of biopharmaceutical drug product.

    Science.gov (United States)

    He, Yan; Friese, Olga V; Schlittler, Michele R; Wang, Qian; Yang, Xun; Bass, Laura A; Jones, Michael T

    2012-11-02

    A methodology based on on-line coupling of size exclusion chromatography (SEC) with mixed-mode liquid chromatography (LC) has been developed. The method allows for simultaneous measurement of a wide range of components in biopharmaceutical drug products. These components include the active pharmaceutical ingredient (protein) and various kinds of excipients such as cations, anions, nonionic hydrophobic surfactant and hydrophilic sugars. Dual short SEC columns are used to separate small molecule excipients from large protein molecules. The separated protein is quantified using a UV detector at 280 nm. The isolated excipients are switched, online, to the Trinity P1 mixed-mode column for separation, and detected by an evaporative light scattering detector (ELSD). Using a stationary phase with 1.7 μm particles in SEC allows for the use of volatile buffers for both SEC and mix-mode separation. This facilitates the detection of different excipients by ELSD and provides potential for online characterization of the protein with mass spectrometry (MS). The method has been applied to quantitate protein and excipients in different biopharmaceutical drug products including monoclonal antibodies (mAb), antibody drug conjugates (ADC) and vaccines. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Specific Antibody Production by Blood B Cells is Retained in Late Stage Drug-naïve HIV-infected Africans

    Directory of Open Access Journals (Sweden)

    Lydie Béniguel

    2004-01-01

    Full Text Available Unseparated peripheral blood mononuclear cells (PBMCs obtained from drug-naïve African individuals living in a context of multi-infections and presenting with high viral load (VL, were cultured in vitro and tested for their ability to produce antibodies (Abs reacting with HIV-1 antigens. Within these PBMCs, circulating B cells were differentiated in vitro and produced IgG Abs against not only ENV, but also GAG and POL proteins. Under similar experimental conditions, HAART treated patients produced Abs to ENV proteins only. The in vitro antibody production by drug-naïve individuals' PBMCs depended on exogenous cytokines (IL-2 and IL-10 but neither on the re-stimulation of reactive cells in cultures by purified HIV-1-gp 160 antigen nor on the re-engagement of CD40 surface molecules. Further, it was not abrogated by the addition of various monoclonal Abs (mAbs to co-stimulatory molecules. This suggests that the in vitro antibody production by drug-naïve individuals' PBMCs resulted from the maturation of already envelope and core antigen-primed, differentiated B cells, presumably pre-plasma cells, which are not known to circulate at homeostasy. As in vitro produced Abs retained the capacity of binding antigen and forming complexes, this study provides pre-clinical support for functional humoral responses despite major HIV- and other tropical pathogen-induced B cell perturbations.

  8. Application of Quality by Design (QbD) Principles to Extractables/Leachables Assessment. Establishing a Design Space for Terminally Sterilized Aqueous Drug Products Stored in a Plastic Packaging System.

    Science.gov (United States)

    Jenke, Dennis

    2010-01-01

    The concept of quality by design (QbD) reflects the current global regulatory thinking related to pharmaceutical products. A cornerstone of the QbD paradigm is the concept of a design space, where the design space is a multidimensional combination of input variables and process parameters that have been demonstrated to provide the assurance of product quality. If a design space can be established for a pharmaceutical process or product, then operation within the design space confirms that the product or process output possesses the required quality attributes. This concept of design space can be applied to the safety (leachables) assessment of drug products manufactured and stored in packaging systems. Critical variables in such a design space would include those variables that affect the interaction of the drug product and its packaging, including (a) composition of the drug product, (b) composition of the packaging system, (c) configuration of the packaging system, and (d) the conditions of contact. This paper proposes and justifies such a leachables design space for aqueous drug products packaged in a specific plastic packaging system. Such a design space has the following boundaries:Aqueous drug products with a pH in the range of 2 to 8 and that contain no polarity-impacting agents such as organic solubilizers and stabilizers (addressing variable a). Packaging systems manufactured from materials that meet the system's existing material specifications (addressing variable b). Nominal fill volumes from 50 to 1000 mL (addressing variable c). Products subjected to terminal sterilization and then stored at room temperature for a period of up to 24 months (addressing variable d). The ramification of such a design space is that any drug product that falls within these boundaries is deemed to be compatible with the packaging system, from the perspective of safety, without the requirement of supporting drug product testing. When drug products are packaged in plastic

  9. Modulation of Cytokine Production by Drugs with Antiepileptic or Mood Stabilizer Properties in Anti-CD3- and Anti-CD40-Stimulated Blood In Vitro

    Directory of Open Access Journals (Sweden)

    Hubertus Himmerich

    2014-01-01

    Full Text Available Increased cytokine production possibly due to oxidative stress has repeatedly been shown to play a pivotal role in the pathophysiology of epilepsy and bipolar disorder. Recent in vitro and animal studies of valproic acid (VPA report antioxidative and anti-inflammatory properties, and suppression of interleukin (IL-6 and tumor necrosis factor (TNF-α. We tested the effect of drugs with antiepileptic or mood stabilizer properties, namely, primidone (PRM, carbamazepine (CBZ, levetiracetam (LEV, lamotrigine (LTG, VPA, oxcarbazepine (OXC, topiramate (TPM, phenobarbital (PB, and lithium on the production of the following cytokines in vitro: interleukin (IL-1β, IL-2, IL-4, IL-6, IL-17, IL-22, and TNF-α. We performed a whole blood assay with stimulated blood of 14 healthy female subjects. Anti-human CD3 monoclonal antibody OKT3, combined with 5C3 antibody against CD40, was used as stimulant. We found a significant reduction of IL-1 and IL-2 levels with all tested drugs other than lithium in the CD3/5C3-stimulated blood; VPA led to a decrease in IL-1β, IL-2, IL-4, IL-6, IL-17, and TNF-α production, which substantiates and adds knowledge to current hypotheses on VPA’s anti-inflammatory properties.

  10. Drug Facts

    Medline Plus

    Full Text Available ... Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used Drugs in the Past Drug Use ... Videos Information About Drugs Alcohol ...

  11. Drug Allergy

    Science.gov (United States)

    ... Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days or ... you take the drug. Drugs commonly linked to allergies Although any drug can cause an allergic reaction, ...

  12. A novel approach to support formulation design on twin screw wet granulation technology: Understanding the impact of overarching excipient properties on drug product quality attributes.

    Science.gov (United States)

    Willecke, N; Szepes, A; Wunderlich, M; Remon, J P; Vervaet, C; De Beer, T

    2018-04-21

    The overall objective of this work is to understand how excipient characteristics influence the drug product quality attributes and process performance of a continuous twin screw wet granulation process. The knowledge gained in this study is intended to be used for Quality by Design (QbD)-based formulation design and formulation optimization. Three principal components which represent the overarching properties of 8 selected pharmaceutical fillers were used as factors, whereas factors 4 and 5 represented binder type and binder concentration in a design of experiments (DoE). The majority of process parameters were kept constant to minimize their influence on the granule and drug product quality. 27 DoE batches consisting of binary filler/binder mixtures were processed via continuous twin screw wet granulation followed by tablet compression. Multiple linear regression models were built providing understanding of the impact of filler and binder properties on granule and tablet quality attributes (i.e. 16 DoE responses). The impact of fillers on the granule and tablet responses was more dominant compared to the impact of binder type and concentration. The filler properties had a relevant effect on granule characteristics, such as particle size, friability and specific surface area. Binder type and concentration revealed a relevant influence on granule flowability and friability as well as on the compactability (required compression force during tableting to obtain target hardness). In order to evaluate the DoE models' validity, a verification of the DoE models was performed with new formulations (i.e. a new combination of filler, binder type and binder concentration) which were initially not included in the dataset used to build the DoE models. The combined PCA (principle component analysis)/DoE approach allowed to link the excipient properties with the drug product quality attributes. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Drug Development Process

    Science.gov (United States)

    ... Preclinical Research Preclinical Research Drugs undergo laboratory and animal testing to answer basic questions about safety. More Information ... Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products

  14. [Survey of synthetic disinfectants in grapefruit seed extract and its compounded products].

    Science.gov (United States)

    Sugimoto, Naoki; Tada, Atsuko; Kuroyanagi, Masanori; Yoneda, Yuko; Yun, Young Sook; Kunugi, Akira; Sato, Kyoko; Yamazaki, Takeshi; Tanamoto, Ken-Ichi

    2008-02-01

    Grapefruit seed extract (GSE), derived from the seeds of grapefruit (Citrus paradisi MCAF.), is listed as a natural food additive in Japan. Products containing GSE are used as disinfectants made from only natural sources, especially after Japanese researchers found that GSE prevents the growth of norovirus. On the other hand, recent overseas studies indicated that synthetic disinfectants, such as benzalkonium and benzethonium chlorides, were present in some commercial GSE products. To confirm the quality of commercial GSE products available in Japanese markets, we carried out comprehensive research to identify the major constituents of commercial GSE products which are used as food additives (13 products from 6 manufacturers), dietary supplements (5 products from 4 manufacturers), cosmetic materials (16 products from 10 manufacturers) and disinfectant or deodorant sprays (7 products from 7 manufacturers). By means of NMR and LC/MS analysis, synthetic disinfectants such as benzethonium or benzalkonium salts were detected in most of the commercial GSE products.

  15. Drug development in neuropsychopharmacology.

    Science.gov (United States)

    Fritze, Jürgen

    2008-03-01

    Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.

  16. 42 CFR 410.29 - Limitations on drugs and biologicals.

    Science.gov (United States)

    2010-10-01

    ... factors, and except for EPO, any drug or biological that can be self-administered. (b) Any drug product that meets all of the following conditions: (1) The drug product was approved by the Food and Drug...) Any drug product that is identical, related, or similar, as defined in 21 CFR 310.6, to a drug product...

  17. [Current cases of falsified medicinal products within the competence of the Federal Institute for Drugs and Medical Devices (BfArM) : Case studies and extent].

    Science.gov (United States)

    Wittstock, Marcus; Paeschke, Norbert

    2017-11-01

    The nature of a falsification of a medicinal product can vary a lot. Therefore the means to detect them and the potential risk to patient safety can also be very different. The whole range of falsification will be described using observed cases from the Federal Institute for Drugs and Medical Devices (BfArM).Based on the relatively low number of detected cases of falsified medicines, the legal supply chain can still be regarded as safe. It has to be assumed that in the illegal supply chain, e. g. illegal internet trade, the majority of the offered medicinal products are not only falsifications due to illegal trade but because they are completely falsified. Therefore there is an especially high risk for the consumer to be harmed by medicinal products that do not fulfil the required specifications.The trend indicates that increased efforts will be necessary to keep the legal supply chain safe and to contain illegal trade with falsifications. The higher federal authorities BfArM, PEI and BVL are involved in this task by coordinating and ensuring the flow of information to the concerned authorities and stakeholders as well as informing the public. Increased efforts are also necessary due to the rising involvement of organised crime in the falsification of medicinal products. A package of measures was enacted with the Falsified Medicines Directive 2011/62/EU to protect the legal supply chain from falsified medicinal products.

  18. Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry

    Science.gov (United States)

    2018-01-01

    Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain. PMID:29436819

  19. 78 FR 51732 - The Food and Drug Administration/European Medicines Agency Orphan Product Designation and Grant...

    Science.gov (United States)

    2013-08-21

    ..., and the FDA Orphan Products Grant program to participants representing pharmaceutical, biotechnology... treatment of a rare disease or condition in order to discuss the processes for putting together an...

  20. United States Food and Drug Administration and Department of Defense shelf-life extension program of pharmaceutical products: progress and promise.

    Science.gov (United States)

    Khan, Saeed R; Kona, Ravikanth; Faustino, Patrick J; Gupta, Abhay; Taylor, Jeb S; Porter, Donna A; Khan, Mansoor

    2014-05-01

    The Department of Defense (DoD)-United States Food and Drug Administration (FDA) shelf-life extension program (SLEP) was established in 1986 through an intra-agency agreement between the DoD and the FDA to extend the shelf life of product nearing expiry. During the early stages of development, special attention was paid to program operation, labeling requirements, and the cost benefits associated with this program. In addition to the substantial cost benefits, the program also provides the FDA's Center for Drug Evaluation and Research with significant scientific understanding and pharmaceutical resource. As a result of this unique resource, numerous regulatory research opportunities to improve public health present themselves from this distinctive scientific database, which includes examples of products shelf life, their long-term stability issues, and various physical and chemical tests to identify such failures. The database also serves as a scientific resource for mechanistic understanding and identification of test failures leading to the development of new formulations or more robust packaging. It has been recognized that SLEP is very important in maintaining both national security and public welfare by confirming that the stockpiled pharmaceutical products meet quality standards after the "expiration date" assigned by the sponsor. SLEP research is an example of regulatory science that is needed to best ensure product performance past the original shelf life. The objective of this article is to provide a brief history and background and most importantly the public health benefits of the SLEP. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  1. Redeployment-based drug screening identifies the anti-helminthic niclosamide as anti-myeloma therapy that also reduces free light chain production

    International Nuclear Information System (INIS)

    Khanim, F L; Merrick, B A M E; Giles, H V; Jankute, M; Jackson, J B; Giles, L J; Birtwistle, J; Bunce, C M; Drayson, M T

    2011-01-01

    Despite recent therapeutic advancements, multiple myeloma (MM) remains incurable and new therapies are needed, especially for the treatment of elderly and relapsed/refractory patients. We have screened a panel of 100 off-patent licensed oral drugs for anti-myeloma activity and identified niclosamide, an anti-helminthic. Niclosamide, at clinically achievable non-toxic concentrations, killed MM cell lines and primary MM cells as efficiently as or better than standard chemotherapy and existing anti-myeloma drugs individually or in combinations, with little impact on normal donor cells. Cell death was associated with markers of both apoptosis and autophagy. Importantly, niclosamide rapidly reduced free light chain (FLC) production by MM cell lines and primary MM. FLCs are a major cause of renal impairment in MM patients and light chain amyloid and FLC reduction is associated with reversal of tissue damage. Our data indicate that niclosamides anti-MM activity was mediated through the mitochondria with rapid loss of mitochondrial membrane potential, uncoupling of oxidative phosphorylation and production of mitochondrial superoxide. Niclosamide also modulated the nuclear factor-κB and STAT3 pathways in MM cells. In conclusion, our data indicate that MM cells can be selectively targeted using niclosamide while also reducing FLC secretion. Importantly, niclosamide is widely used at these concentrations with minimal toxicity

  2. Understanding API-polymer proximities in amorphous stabilized composite drug products using fluorine-carbon 2D HETCOR solid-state NMR.

    Science.gov (United States)

    Abraham, Anuji; Crull, George

    2014-10-06

    A simple and robust method for obtaining fluorine-carbon proximities was established using a (19)F-(13)C heteronuclear correlation (HETCOR) two-dimensional (2D) solid-state nuclear magnetic resonance (ssNMR) experiment under magic-angle spinning (MAS). The method was applied to study a crystalline active pharmaceutical ingredient (API), avagacestat, containing two types of fluorine atoms and its API-polymer composite drug product. These results provide insight into the molecular structure, aid with assigning the carbon resonances, and probe API-polymer proximities in amorphous spray dried dispersions (SDD). This method has an advantage over the commonly used (1)H-(13)C HETCOR because of the large chemical shift dispersion in the fluorine dimension. In the present study, fluorine-carbon distances up to 8 Å were probed, giving insight into the API structure, crystal packing, and assignments. Most importantly, the study demonstrates a method for probing an intimate molecular level contact between an amorphous API and a polymer in an SDD, giving insights into molecular association and understanding of the role of the polymer in API stability (such as recrystallization, degradation, etc.) in such novel composite drug products.

  3. An investigation into drug products withdrawn from the EU market between 2002 and 2011 for safety reasons and the evidence used to support the decision-making.

    Science.gov (United States)

    McNaughton, Rhian; Huet, Gwenaël; Shakir, Saad

    2014-01-15

    The objective of this study was to determine the nature of evidence used to support the withdrawal of marketing authorisations of drug products for safety reasons throughout the European Union (EU) between 2002 and 2011. Products withdrawn, either by a medicines agency or a marketing authorisation holder, during the period 2002-2011 were identified by conducting detailed searches of the WHO, the European Medicines Agency (EMA) and national medicines agency websites throughout the EU plus Norway, Iceland and Liechtenstein. The scientific evidence used to support the decision was identified from a search within PubMed, the EMA and national medicines agencies websites. Information about spontaneous case reports entered into EudraVigilance and unavailable on the EMA website was received by email from the EMA. 19 drugs were withdrawn from the market, throughout the EU, for safety reasons from 2002 to 2011. Case reports were cited in 95% of withdrawals (18/19) and case-control studies (4/19), cohort studies (4/19), randomised controlled trials (RCTs) (12/19) or meta-analysis (5/19) were cited in 63% of withdrawals (12/19). Cardiovascular events or disorders were the main reason for withdrawal (9/19), followed by hepatic disorders (4/19) and neurological or psychiatric disorders (4/19). This study has shown that the level of evidence used to support drug withdrawal has improved during the past 10 years, with an increased use of case-control studies, cohort studies, RCTs and meta-analyses. This research has demonstrated that such studies have contributed to decision-making in almost two-thirds of cases.

  4. Activities and influence of veterinary drug marketers on antimicrobial usage in livestock production in Oyo and Kaduna States, Nigeria

    OpenAIRE

    Olufemi Ernest Ojo; Olajoju Jokotola Awoyomi; Eniola Fabusoro; Morenike Atinuke Dipeolu

    2017-01-01

    Antimicrobial usage in animals contributes to the emergence of antimicrobial resistant bacterial strains. Investigations were carried out on how the characteristics, knowledge, attitude and practices of antimicrobial marketers influenced antimicrobials usage in animal production in Oyo and Kaduna States, Nigeria. Focus group discussions, in-depth interviews and structured questionnaires were used to gather information about the characteristics and activities of antimicrobial marketers. Overal...

  5. 21 CFR 330.5 - Drug categories.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Drug categories. 330.5 Section 330.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN...) Stimulants. (r) Antitussives. (s) Allergy treatment products. (t) Cold remedies. (u) Antirheumatic products...

  6. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  7. Drug Abuse

    Science.gov (United States)

    ... Cocaine Heroin Inhalants Marijuana Prescription drugs, including opioids Drug abuse also plays a role in many major social problems, such as drugged driving, violence, stress, and child abuse. Drug abuse can lead to ...

  8. Drug Facts

    Medline Plus

    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...

  10. Club Drugs

    Science.gov (United States)

    ... uses. Other uses of these drugs are abuse. Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can ...

  11. Analytical approaches for the detection of epoxides and hydroperoxides in active pharmaceutical ingredients, drug products and herbals.

    Science.gov (United States)

    Elder, D P; Snodin, D; Teasdale, A

    2010-04-06

    This review summarizes the analytical approaches reported in the literature relating to epoxide and hydroperoxide impurities. It is intended that it should provide guidance for analysts faced by the need to control such impurities, particularly where this is due to concerns relating to their potential genotoxicity. An extensive search of the literature relating to this class of impurities revealed a large number of references relating to analysis of epoxides/hydroperoxides associated with herbal remedies. Given the general applicability of the analytical methodology and due to the widespread use of herbal products the authors decided to include herbal medicines in this review. The review also reflects on the very different approaches taken in terms of the assessment/control of genotoxic impurities for such herbal remedies to that required for pharmaceutical products. Copyright 2009 Elsevier B.V. All rights reserved.

  12. Isolation and identification of Staphylococcus aureus from milk and milk products and their drug resistance patterns in Anand, Gujarat

    Directory of Open Access Journals (Sweden)

    M. N. Brahmbhatt

    2013-02-01

    Full Text Available Aim: The study was carried out with aim to isolate Staphylococcus aureus from milk and milk products (pedha and curd and determine antibiogram pattern of S. aureus isolates. Materials and Methods: During 9 months duration of study a total of 160 milk and milk product samples (pedha and curd were collected from different places in and around Anand city such as milk collection centre of Co-operative milk dairies, cattle farms, individual household, milk vendors and sweet shops. The samples were collected under aseptic precautions and were enriched in Peptone Water (PW followed by direct plating on selective media viz. Baird-Parker Agar. The presumptive S. aureus isolates were identified by biochemical tests. Antibiogram pattern of S. aureus to antimicrobial agents were evaluated by disk diffusion method. Results: Analysis of result revealed that out of total 160 samples of milk (100 and milk products i.e. curd (30 and pedha (30 resulted in the isolation of 10 isolates (6.25 % of S. aureus. In the present study S. aureus isolates were found variably resistant to the antibiotics tested. The S. aureus isolates showed highest sensitivity towards cephalothin (100.00 %, co-trimoxazole (100.00 %, cephalexin (100.00 % and methicillin (100.00 % followed by gentamicin (90.00 %, ciprofloxacin (80.00 %, oxacillin (70.00 %, streptomycin (60.00 % and ampicillin (60.00 %. The pattern clearly indicated that the overall high percent of S. aureus isolates were resistant to Penicillin-G (100.00 % followed by ampicillin (40.00 %, oxytetracycline and oxacillin (20.00 % and streptomycin and gentamicin (10.00 % Conclusions: Results clearly suggested a possibility of potential public health threat of S. aureus resulting from contamination of milk and milk products with pathogenic bacteria is mainly due to unhygienic processing, handling and unhygienic environment. [Vet World 2013; 6(1.000: 10-13

  13. The biopharmaceutics of successful controlled release drug product: Segmental-dependent permeability of glipizide vs. metoprolol throughout the intestinal tract.

    Science.gov (United States)

    Zur, Moran; Cohen, Noa; Agbaria, Riad; Dahan, Arik

    2015-07-15

    The purpose of this work was to study the challenges and prospects of regional-dependent absorption in a controlled-release scenario, through the oral biopharmaceutics of the sulfonylurea antidiabetic drug glipizide. The BCS solubility class of glipizide was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in-vitro (PAMPA and Caco-2) and in-vivo in rats. Metoprolol was used as the low/high permeability class boundary marker. Glipizide was found to be a low-solubility compound. All intestinal permeability experimental methods revealed similar trend; a mirror image small intestinal permeability with opposite regional/pH-dependency was obtained, a downward trend for glipizide, and an upward trend for metoprolol. Yet the lowest permeability of glipizide (terminal Ileum) was comparable to the lowest permeability of metoprolol (proximal jejunum). At the colon, similar permeability was evident for glipizide and metoprolol, that was higher than metoprolol's jejunal permeability. We present an analysis that identifies metoprolol's jejunal permeability as the low/high permeability class benchmark anywhere throughout the intestinal tract; we show that the permeability of both glipizide and metoprolol matches/exceeds this threshold throughout the entire intestinal tract, accounting for their success as controlled-release dosage form. This represents a key biopharmaceutical characteristic for a successful controlled-release dosage form. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Productivity

    DEFF Research Database (Denmark)

    Spring, Martin; Johnes, Geraint; Hald, Kim Sundtoft

    Productivity is increasingly critical for developed economies. It has always been important: as Paul Krugman puts it, “Productivity isn’t everything, but in the long run it is almost everything. A country’s ability to improve its standard of living over time depends almost entirely on its ability...... to raise its output per worker”(Krugman, 1994). Analyses of productivity have, by and large, been the preserve of economists. Operations Management (OM) is rooted in a similar concern for the efficient use of scarce resources; Management Accounting (MA) is concerned with the institutionalised measurement...... and management of productivity. Yet the three perspectives are rarely connected. This paper is a sketch of a literature review seeking to identify, contrast and reconcile these three perspectives. In so doing, it aims to strengthen the connections between policy and managerial analyses of productivity....

  15. High-throughput screening platform for natural product-based drug discovery against 3 neglected tropical diseases: human African trypanosomiasis, leishmaniasis, and Chagas disease.

    Science.gov (United States)

    Annang, F; Pérez-Moreno, G; García-Hernández, R; Cordon-Obras, C; Martín, J; Tormo, J R; Rodríguez, L; de Pedro, N; Gómez-Pérez, V; Valente, M; Reyes, F; Genilloud, O; Vicente, F; Castanys, S; Ruiz-Pérez, L M; Navarro, M; Gamarro, F; González-Pacanowska, D

    2015-01-01

    African trypanosomiasis, leishmaniasis, and Chagas disease are 3 neglected tropical diseases for which current therapeutic interventions are inadequate or toxic. There is an urgent need to find new lead compounds against these diseases. Most drug discovery strategies rely on high-throughput screening (HTS) of synthetic chemical libraries using phenotypic and target-based approaches. Combinatorial chemistry libraries contain hundreds of thousands of compounds; however, they lack the structural diversity required to find entirely novel chemotypes. Natural products, in contrast, are a highly underexplored pool of unique chemical diversity that can serve as excellent templates for the synthesis of novel, biologically active molecules. We report here a validated HTS platform for the screening of microbial extracts against the 3 diseases. We have used this platform in a pilot project to screen a subset (5976) of microbial extracts from the MEDINA Natural Products library. Tandem liquid chromatography-mass spectrometry showed that 48 extracts contain potentially new compounds that are currently undergoing de-replication for future isolation and characterization. Known active components included actinomycin D, bafilomycin B1, chromomycin A3, echinomycin, hygrolidin, and nonactins, among others. The report here is, to our knowledge, the first HTS of microbial natural product extracts against the above-mentioned kinetoplastid parasites. © 2014 Society for Laboratory Automation and Screening.

  16. Iodate oxidation of N-Acetyl L-Cysteine: Application in drug determination and characterization of its oxidation and degradation product by mass spectrometry

    International Nuclear Information System (INIS)

    Siddiqui, Masom Raza; Wabaiduri, Saikh Mohammas; Alothman, Zied A; Rahman, Habibur; Alam, Sarfarah; Ali, Sajid

    2014-01-01

    A kinetic spectrophotometric method based on the initial rate measurement has been developed for the determination of N-acetyl L-cysteine. The developed method is based on the oxidation of N-acetyl L-cysteine with iodate. The reaction product was studied and characterized using the mass spectrometry and the structure of the product was proposed. From the mass spectrometric studies it was concluded that the oxidation of the drug resulted in the formation of a disulfide. The developed method was validated as per the guidelines of international conference on harmonization. The developed initial rate method was found to be linear in the concentration range of 1.25 - 30μg ml-1. The detection and quantitation limits were found to be 0.018 and 0.056 μG ml -1 . In the current study, the degradation product of N-acetyl L cysteine was also prepared and identified using mass spectrometry. Keywords: N- acetyl cysteine, Initial rate method, Spectrophotometry, mass spectrometry

  17. Product Failures in Respirators and Consumables: Analysis of Field Safety Notices of 2005-2013 Publicized by the Federal Institute for Drugs and Medical Devices in Germany.

    Science.gov (United States)

    Hannig, Jürgen; Siekmeier, Rüdiger

    2015-01-01

    The current European system governed by the three EC directives 93/42/EEC (Medical Device Directive), 98/79/EC (In-Vitro Diagnostic Directive) and 90/385/EEC (Active Implantable Medical Device Directive) regulates marketing and post-market surveillance of medical devices in the European Economic Area (EEA). In cases of incidents raising the field safety corrective actions (FSCA), manufacturers have to inform the responsible Competent Authority (CA; in Germany this is the Federal Institute for Drugs and Medical Devices, BfArM) and the public by field safety notices (FSN). In this study we analyzed FSN of respirators and consumables directly required for their function, whereas devices for anesthesia and gas delivery were excluded. FSCA and FSN of 2005-2013 publicized by BfArM for the included products were analyzed with respect to the MEDDEV 2.12-1 rev. 8. In total, 60 FSCA were publicized. German and English FSN were found in 59/53 cases, respectively. FSN were clearly characterized as FSN in 44/38 cases and declaration of the type of action in 45/44 cases, respectively. Product names were provided in all cases. Lot numbers or other information for product characterization were available in 7/7 and 43/40 cases, respectively. Detailed information regarding FSCA and product malfunction was found in all cases. Information on product related risks with previous use of affected devices was provided in 42/38 cases. In 53/53 cases manufacturers provided information to mitigate product related risks. Requests to pass FSN to persons needing awareness in the organization were found in 27/24 cases. Contact data were provided in 53/48 cases, respectively. Confirmation that a CA was informed was found in 28/26 cases and in 19/15 cases a customer confirmation was included. The identified risks were: total loss of function (19/16), short circuit (1/1) and burn (3/3), and inhalation of foreign particles (1/1) which might cause severe risk to patients and users. The most frequent

  18. Enantiomeric separation of pharmaceutically important drug intermediates using a Metagenomic lipase and optimization of its large scale production.

    Science.gov (United States)

    Kumar, Rakesh; Banoth, Linga; Banerjee, Uttam Chand; Kaur, Jagdeep

    2017-02-01

    In the present study, efficient enzymatic methods were developed using a recombinant metagenomic lipase (LipR1) for the synthesis of corresponding esters by the transesterification of five different pharmaceutically important secondary alcohols. The recombinant lipase (specific activity=87m6U/mg) showed maximum conversion in presence of ionic liquid with Naphthyl-ethanol (eeP=99%), Indanol and Methyl-4 pyridine methanol (eeS of 98% and 99%) respectively in 1h. Vinyl acetate was found as suitable acyl donor in transesterification reactions. It was interesting to observe that maximum eeP of 85% was observed in just 15min with 1-indanol. As this enzyme demonstrated pharmaceutical applications, attempts were made to scale up the enzyme production on a pilot scale in a 5litre bioreactor. Different physical parameters affecting enzyme production and biomass concentration such as agitation rate, aeration rate and inoculum concentration were evaluated. Maximum lipase activity of 8463U/ml was obtained at 7h of cultivation at 1 lpm, 300rpm and 1.5% inoculum. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Effects of temperature and NaCl on the formation of 3-MCPD esters and glycidyl esters in refined, bleached and deodorized palm olein during deep-fat frying of potato chips.

    Science.gov (United States)

    Wong, Yu Hua; Muhamad, Halimah; Abas, Faridah; Lai, Oi Ming; Nyam, Kar Lin; Tan, Chin Ping

    2017-03-15

    The effects of frying duration, frying temperature and concentration of sodium chloride on the formation of 3-monochloropropane-1,2-diol (3-MCPD) esters and glycidyl esters (GEs) of refined, bleached and deodorized (RBD) palm olein during deep-fat frying (at 160°C and 180°C) of potato chips (0%, 1%, 3% and 5% NaCl) for 100min/d for five consecutive days in eight systems were compared in this study. All oil samples collected after each frying cycle were analyzed for 3-MCPD esters, GEs, free fatty acid (FFA) contents, specific extinction at 232 and 268 nm (K 232 and K 268 ), p-anisidine value (pAV), and fatty acid composition. The 3-MCPD ester trend was decreasing when the frying duration increased, whereas the trend was increasing when frying temperature and concentration of NaCl increased. The GEs trend was increasing when the frying temperature, frying duration and concentration of NaCl increased. All of the oil qualities were within the safety limit. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. The Budding Yeast “Saccharomyces cerevisiae” as a Drug Discovery Tool to Identify Plant-Derived Natural Products with Anti-Proliferative Properties

    Directory of Open Access Journals (Sweden)

    Bouchra Qaddouri

    2011-01-01

    Full Text Available The budding yeast Saccharomyces cerevisiae is a valuable system to study cell-cycle regulation, which is defective in cancer cells. Due to the highly conserved nature of the cell-cycle machinery between yeast and humans, yeast studies are directly relevant to anticancer-drug discovery. The budding yeast is also an excellent model system for identifying and studying antifungal compounds because of the functional conservation of fungal genes. Moreover, yeast studies have also contributed greatly to our understanding of the biological targets and modes of action of bioactive compounds. Understanding the mechanism of action of clinically relevant compounds is essential for the design of improved second-generation molecules. Here we describe our methodology for screening a library of plant-derived natural products in yeast in order to identify and characterize new compounds with anti-proliferative properties.