Hydrogen-bonded interpolymer complexes as materials for pharmaceutical applications

Association of poly(carboxylic acids) and non-ionic polymers in solutions via hydrogen bonding results in formation of novel polymeric materials-interpolymer complexes. These materials can potentially be used for design of novel mucoadhesive dosage forms, development of solid drug dispersions and solubilisation of poorly soluble drugs, encapsulation technologies, preparation of nanoparticles, hydrogels, in situ gelling systems and electrically erodible materials. This review is an attempt to analyse and systematise existing literature on pharmaceutical application of hydrogen-bonded interpolymer complexes. (c) 2007 Elsevier B.V All rights reserved.

Determination of ciclopirox olamine in pharmaceutical products by capillary electrophoresis with capacitively coupled contactless conductivity detection

This paper describes the determination of ciclopirox olamine in pharmaceutical formulations using capillary electrophoresis with capacitively coupled contactless conductivity detection. In an alkaline medium, ciclopirox olamine is converted into an anionic species and its detection is possible in capillary electrophoresis with capacitively coupled contactless conductivity detection without an electroosmotic flow modifier, because it is a low-mobility species. A linear working range from 2.64 to 264 mu g/mL in sodium hydroxide electrolyte as well as low detection limit (0.39 mu g/mL) and a good repeatability (RSD = 3.4% for 264 mu g/mL ciclopirox solution (n = 10)) were achieved. It was also possible to determine olamine in its cationic form when acetic acid was used as the electrolyte solution. The results obtained include a linear range from 26.4 to 184.8 mu g/mL and a detection limit of 2.6 mu g/mL olamine. The proposed methods were applied to the analysis of commercial pharmaceutical products and the results were compared with the values indicated by the manufacturer as well as those obtained using a titrimetric method recommended by American Pharmacopoeia.

Applicatiion of Almost ideal demand system for a pharmaceutical

This thesis is an application of the Almost Ideal Demand System approach of Deaton and Muellbauer,1980, for a particular pharmaceutical, Citalopram, in which GORMAN´s (1971) multi-stage budgeting approach is applied basically since it is one of the most useful approach in estimating demand for differentiated products. Citalopram is an antidepressant drug that is used in the treatment of major depression. As for most other pharmaceuticals whose the patent has expired, there exist branded and generic versions of Citalopram. This paper is aimed to define its demand system with two stage models for the branded version and five generic versions, and to show whether generic versions are able to compete with the branded version. I calculated the own price elasticities, and it made me possible to compare and make a conclusion about the consumers’ choices over the brand and generic drugs. Even though the models need for being developed with some additional variables, estimation results of models and uncompensated price elasticities indicated that the branded version has still power in the market, and generics are able to compete with lower prices. One important point that has to be taken into consideration is that the Swedish pharmaceutical market faced a reform on October 1, 2002, that aims to make consumer better informed about the price and decrease the overall expenditures for pharmaceuticals. Since there were not significantly enough generic sales to take into calculation before the reform, my paper covers sales after the reform.

Pharmaceutical patent bargains: the Brazilian experience

In the backdrop of the strict patent regime flatly adopted by the World Trade Organization (WTO) for all countries, a few countries constantly challenge this system through aggressive patent bargains. Within the pharmaceutical sector, noticeably, some countries now threaten to issue or otherwise actually issue compulsory licenses that may sway large pharmaceutical companies into selling drugs with large discounts or into granting voluntary licenses domestically. That is conspicuously the negotiation strategy adopted by Brazil in its negotiations with big international pharmaceutical companies.This paper explains Brazil’s aggressive bargaining approach based on an analysis of two aspects of its political economy. The first has to do with the international context of patent bargaining in the post-WTO era. Accordingly, the existence of large and fast growing domestic markets position countries such as Brazil as strategic destinations for Foreign Direct Investment (FDI) and trade. Together with an absence of a propensity to innovate in pharmaceutical products, these conditions boost Brazil’s bargaining power for issuing compulsory licenses over pharmaceutical products. The second aspect is related to political economy dynamics inside Brazil. Accordingly, the political framework in Brazil undermines long-term policies and favors short-sighted ones also vis-a-vis R&D investments in the pharmaceutical industry. This remains true regardless of the strictness of the patent regime in place. The lesson of Brazil is relevant arguably for other more powerful developing countries which presently examine Brazil's approach while further challenging the WTO's strict patent policy for the future.

Does humor work in advertising of pharmaceutical products?

This thesis aims to evaluate whether humorous television commercials (TVCs) work for non-prescription drugs, known as “over-the-counter” (OTC). The construct humor in advertising is controversial since it involves complex and broad typology, and depends on the audience characteristics. Several studies within different product categories indicated that some consumer goods are better suited for humorous TVCs, while others, such as OTC drugs, may not take advantage from it. Paradoxically, drug announcers spend billions of dollars worldwide in humorous OTC ads. An experiment with real consumers was designed as between-and-within-subjects, to test three hypotheses. Sixty women were exposed to pairs of humorous and non-humorous TVCs, for each of the three drug categories (analgesics, vitamins, and laxatives). We used fictional brand names and real ads, and measured four dependant variables: attitude toward the advertising (AAD), attitude toward the brand (ABR), purchase intention (PI), and brand choice (BC), after subjects being exposed to manipulations of two independent variables: humorous vs. non-humorous TV commercials, for the drug categories. Conditional logit model confirmed that humor does not help to persuade respondents, whose choices, attitudes, and purchase intention were less favorable with humorous TVCs, in comparison to non-humorous executions. Future research is presented regarding marketing for pharmaceutical products.

Preparation of polymeric micelles for use as carriers of tuberculostatic drugs

Purpose: This paper focuses on the characterization of polymeric micelle-forming tuberculostatic prodrugs and the antimycobacterial activity of these prodrugs.Method: By the condensation of hydroxymethylpyrazinamide, isoniazid and rifampin with free carboxyl groups on the copolymer poly(ethyleneglycol)-poly(aspartic acid), micelle-forming carrier-drug conjugates were obtained. These micelles were characterized by dynamic light scattering, to measure the micelle diameter; by acid-base titration, to determine the percentage of carboxylic groups occupied by the tuberculostatic; by Sudan III solubility tests, to estimate the critical micelle concentration (CMC); and visual control and spectrophotometric measurement, to determine the stability of micelles. These micelles were tested in vitro against several Mycobacterium strains.Results: As expected, the size and distribution of the micelle-forming tuberculostatic prodrugs found to be small (78.2nm, 84.2nm and 98.9 nm) while the level of the drug conjugated was high (65.02-85.7%). Furthermore, the micelles were stable in vitro, exhibiting a low level of CMC and stronger antimycobacterial activity than the original drugs.Conclusion: the results demonstrate that polymeric micelles can be used as efficient carriers for drugs, which alone, exhibit undesired pharmacokinetics, poor solubility, and low stability. The synthesized micelle-forming tuberculostatic prodrugs opens a perspective of alternative prodrugs that prolong action and decrease the toxicity of the tuberculostatic drugs of choice.

Propolis: Is there a potential for the development of new drugs?

Introduction: Propolis has plenty of biological and pharmacological properties and its mechanisms of action have been widely investigated in the last years, using different experimental models in vitro and in vivo. Researchers have been interested in the investigation of isolated compounds responsible for propolis action; however, there is lack of clinical research on the effects of propolis.Strategy and objectives: Since propolis-containing products have been marketed and humans have used propolis for different purposes, the goal of this review is to discuss the potential of propolis for the development of new drugs, by comparing data from the literature that suggest candidate areas for the establishment of drugs against tumors, infections, allergy, diabetes, ulcers and with immunomodulatory action.Conclusions: The efficacy of propolis in different protocols in vitro and in vivo suggests its therapeutic properties, but before establishing a strategy using this bee product, it is necessary to study: (a) the chemical nature of the propolis sample. (b) Propolis efficacy should be compared to well-established parameters, e.g. positive or negative controls in the experiments. Moreover, possible interactions between propolis and other medicines should be investigated in humans as well. (c) Clinical investigation is needed to evaluate propolis potential in patients or healthy individuals, to understand under which conditions propolis may promote health. Data point out the importance of this research field not only for the readers and researchers in the scientific community waiting for further clarification on the potential of propolis but also for the pharmaceutical industry that looks for new drugs. (C) 2010 Elsevier B.V. All rights reserved.

Detection of propranolol in pharmaceutical formulations by diffuse reflectance spectroscopy

This paper describes an analytical reflectometric method that has an objective not only the industrial quality control but also to detect possible falsifications and/or adulterations of propranolol in pharmaceutical formulations. The method is based on the diffuse reflectance measurements of the colored product (III) of the spot test reaction between propranolol hydrochloride (I) and 2,6-dichloroquinone-4-chloroimide (II) using filter paper as solid support. Spot test conditions have been investigated using experimental design in order to identify and optimize the critical factors. The factors evaluated were DCQ concentration, propranolol solvent and DCQ solvent. The best reaction conditions were achieved with the addition of 30 mu L, of propranolol solution in ethanol 35% (v/v) and 30 mu L of DCQ solution at 70 mg mL(-1) in acetone, in this order. All reflectance measurements were carried out at 500 nm and the linear range was from 8.45 x 10(-4) to 8.45 x 10(-2) mol L-1 (r= 0.998). The limit of detection was 1.01 x 10(-4) mol L-1. No interference was observed from the assessed excipients and drugs. The method was applied to determine propranolol in commercial brands of pharmaceuticals. The results obtained by the proposed method were favorably compared with those given by the British Pharmacopoeia procedure. (C) 2007 Elsevier B.V. All rights reserved.

Electrochemical, Spectrophotometric and Liquid-Chromatographic Approaches for Analysis of Tropical Disease Drugs

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Sequential injection analysis system with spectrophotometric detection for determination of norfloxacin and ciprofloxacin in pharmaceutical formulations

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Flow-injection spectrophotometric determination of tetracycline and doxycycline in pharmaceutical formulations using chloramine-T as oxidizing agent

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Patents of drugs extracted from Brazilian medicinal plants

Background: Plants synthesise a vast repertoire of chemicals with various biological activities. Brazilian enormous botanical diversity facilitates the development of novel ethical drugs for the treatment of diseases in humans. Objective: To present therapeutic patent applications comprising Brazilian native plants published in the 2003 - 2008 period in light of legal aspects of patentability of biodiversity and public health concerns. Methods: Therapeutic patent applications related to Brazilian medicinal plants available at both the European Patent Office and the Brazilian National Institute of industrial Property databases were reviewed. Results/conclusion: Twenty-five patents are presented, most of which concern inflammatory, allergic, parasitic, infectious or digestive diseases, including extracts from Carapa guianensis, Copaifera genus, Cordia verbenacea, Erythrina mulungu, Physalis angulata and other pharmaceutical compositions with antileishmanial, antimalarial or trypanocidal activity. Brazilian research centres and universities are responsible for most of these inventions.

Clinical research on new drugs (Phase I). Profile of scientific publications: data from the pre-clinical phase and bioethical aspects

OBJETIVO: Traçar o perfil das publicações científicas de fase I e procurar saber se a publicação oferece dados da fase pré-clínica com ênfase nos aspectos bioéticos. MÉTODOS: Foram analisados 61 artigos científicos publicados no ano de 2007, que relatam pesquisas envolvendo seres humanos com novos fármacos, medicamentos ou vacinas em fase I. Foi elaborado um roteiro para coleta de dados, com o qual fosse possível analisar e avaliar os artigos científicos. O roteiro contempla itens referentes à fase pré-clínica (associados à fase clínica) e itens referentes às características da amostra. RESULTADOS: Nos artigos analisados, a maioria das pesquisas foi realizada nos EUA. Devido ao grande número de publicações destinadas às doenças oncológicas a maioria delas foi realizada com voluntários doentes. Quanto às informações sobre a fase pré-clínica presente nas publicações de fase I observamos que são pobres ou inexistentes. Mesmo que os autores julguem a pesquisa fase I como promissora e sugiram estudos futuros de fase II, ao leitor não é possível este mesmo julgamento pela escassez de informações da fase pré-clínica. CONCLUSÃO: O perfil das publicações levanta dados que merecem reflexão e análise para melhor avaliação do que está ocorrendo com as publicações de fase I.

Effects of tea from Turnera ulmifolia L. on mouse gastric mucosa support the Turneraceae as a new source of antiulcerogenic drugs

Turnera ulmifolia is a plant belonging to the family Turneraceae, popularly known in Brazil as chanana. This species is distributed from Guyana to southern Brazil where it is considered a weed. The plant occurs in tropical rain forest, fields, and gardens. Chanana tea is used in Brazilian folk medicine for the treatment of diseases related mainly to gastric dysfunction including gastric and duodenal ulcers. In this study, the ability of a lyophilized infusion, as an aqueous fraction (AqF) of the aerial parts of T. ulmifolia, was investigated for its ability to prevent ulceration of the gastric and duodenal mucosa was examined in mice and rats, respectively. The AqF significantly reduced the formation of lesions associated with HCl/ethanol administration by 39% and 46%, respectively, at doses of 500 mg/kg and 1000 mg/kg, p.o. The AqF also significantly reduced the incidence of gastric lesions induced by a combination of indomethacin and bethanechol by 58% and 72% at doses of 500 mg/kg and 1000 mg/kg, respectively. In stress-induced gastric ulcer, the inhibition by the AqF was 48%, 57%, and 58% at doses of 250 mg/kg, 500 mg/kg, and 1000 mg/kg, respectively (p<0.05). A pyloric ligature experiment showed that the highest dose of the AqF significantly affected the gastric juice parameters by increasing the pH from 2.5 (control) to 5.3 and decreasing the acid output from 11.3 (control) to 3.7 mEq/ml/4 h. The AqF had no significant effect on duodenal ulcers induced by cysteamine. Preliminary phytochemical screening confirmed that flavonoids were the major constituents of the AqF of T. ulmifolia. These results indicate that this extract has a significant antiulcerogenic effect, as popularly believed.

Design and ergonomics of package inserts of drugs in Brazil: a reality in construction

This research deals with the design of leaflets of medicines, evidencing the problems resulting from the lack of Brazilian normalization to promote the use of the graphical representation of instructional texts warnings. It approaches studies related to the effectiveness and efficiency of information systems, highlighting the semiotics and the cultural and informational ergonomics. The analysis of the context uses as method, an analytical study on selected warnings of thirty leaflets of medicines, followed by interviews lead with the public managers involved with the regulation of the pharmaceutical companies, and two experiments with users performed in city of Recife, in State of Pernambuco: one aiming at to identify how they interact with the leaflets of medicines, and the second one testing their understanding concerning standardized illustrations in the United States and the South Africa. The results show the need for improvements in presentation and graphic representation of leaflets of medicines, powering them to the role of communication, to ensure the consumption of medicine safely by its users. The conclusion congregates parameters and recommendations for the graphic representation of warnings in leaflets of medicines in Brazil.