Research progress on the preparation and application of flavonoid nanocrystals / 浙江大学学报·医学版

Flavonoids have been reported to possess significant pharmacological activities,such as antioxidant, anti-inflammatory and anticancer effects. However, the low solubility and low bioavailability limits their clinical application. Nanocrystal technology can solve the delivery problems of flavonoids by reducing particle size, increasing the solubility of insoluble drugs and improving their bioavailability. This article summaries nanosuspension preparation methods and the stabilizers for flavonoid nanocrystals, and reviews the drug delivery routes including oral, Injection and transdermal of flavonoid nanocrystals, to provide information for further research on nanocrystal delivery system of flavonoids.

The relationships among Flory-Huggins specific interaction parameters, maximum amorphous capacity, and solid-state interactions of spray dried amorphous drug dispersions with conventional and novel pharmaceutical polymers / Las relaciones entre los parámetros de interacción específicos de Flry-Huggins, la capacidad amorfa máxima y las interacciones en estado sólido de las dispersiones de fármacos amorfos secados por aspersión con polímeros farmacéuticos convencionales y nuevos

This study evaluated the specific interactions between drug and polymers in amorphous spray dried dispersions (SDDs). Four Biopharmaceutics Classification System (BCS) II class drugs were evaluated. Binary and ternary SDDs were manufactured with conventional polymers and arabinogalactan. Specific interaction parameters between drug and polymer were determined using theoretical calculations and DSC data. Analytical methods were used to evaluate solid and solution state interactions. Maximum amorphous content for each formulation was calculated using DSC. Flory-Huggins Specific Interaction Parameters were calculated. Negative specific parameters were associated with solid-state interactions and improved capacity of drug in the amorphous state. Ternary SDDs containing drug, polymer, and arabinogalactan displayed similar hydrogen bonding as was observed with binary SDDs. Solution-state interactions observed in binary systems may be used in tertiary systems to improve the amorphous drug capacity and improved dissolution compared to the binary. The resultant tertiary systems are an improvement over binary drug polymer systems.

Este estudio evaluó las interacciones específicas entre el fármaco y los polímeros en dispersiones amorfas secadas por pulverización (SDD). Se evaluaron cuatro fármacos de clase II del Sistema de Clasificación Biofarmacéutica (BCS). Los SDD binarios y ternarios se fabricaron con polímeros convencionales y arabinogalactano. Los parámetros de interacción específicos entre el fármaco y el polímero se determinaron utilizando cálculos teóricos y datos de DSC. Se utilizaron métodos analíticos para evaluar las interacciones del estado sólido y de la solución. El contenido amorfo máximo para cada formulación se calculó usando DSC. Se calcularon los parámetros de interacción específicos de Flory-Huggins. Los parámetros específicos negativos se asociaron con interacciones en estado sólido y una capacidad mejorada del fármaco en el estado amorfo. Los SDD ternarios que contienen fármaco, polímero y arabinogalactano mostraron enlaces de hidrógeno similares a los observados con los SDD binarios. Las interacciones de estado de solución observadas en sistemas binarios pueden usarse en sistemas terciarios para mejorar la capacidad del fármaco amorfo y mejorar la disolución en comparación con el binario. Los sistemas terciarios resultantes son una mejora con respecto a los sistemas de polímeros de fármacos binarios.

Incompatibilidades medicamentosas em centro de tratamento intensivo adulto de um hospital universitário / Drug incompatibilities in the adult intensive care unit of a university hospital

RESUMO Objetivos: Identificar as incompatibilidades físico-químicas entre medicamentos administrados por via intravenosa em pacientes internados em um centro de tratamento intensivo adulto, bem como realizar orientações farmacêuticas para a administração de medicamentos incompatíveis. Métodos: Estudo transversal, prospectivo, de caráter quantitativo, realizado no período de julho a setembro de 2015. As incompatibilidades foram identificadas a partir da análise das prescrições dos pacientes disponíveis no sistema on-line do hospital. Foi realizada uma intervenção farmacêutica por meio de orientações quanto à preparação e à administração dos medicamentos incompatíveis. Após, verificou-se a adesão dessas orientações por parte da equipe da enfermagem. Resultados: Foram analisadas 100 prescrições; destas, 68 apresentaram incompatibilidade entre os medicamentos intravenosos prescritos. Foram encontradas 271 incompatibilidades, com média de 4,0 ± 3,3 incompatibilidades por prescrição. As incompatibilidades mais frequentes foram entre midazolam e hidrocortisona (8,9%), cefepime e midazolam (5,2%) e hidrocortisona e vancomicina (5,2%). Os medicamentos mais envolvidos em incompatibilidades foram o midazolam, a hidrocortisona e a vancomicina. As incompatibilidades foram mais frequentes entre um medicamento administrado por infusão contínua com outro de forma intermitente (50%). Das 68 prescrições que geraram orientação farmacêutica, 45 (66,2%) foram totalmente realizadas pela equipe de enfermagem. Conclusão: Os pacientes em cuidados intensivos estiveram sujeitos a uma elevada ocorrência de incompatibilidades. As incompatibilidades medicamentosas podem ser identificadas e evitadas com a presença do farmacêutico na equipe multidisciplinar, diminuindo a ocorrência de efeitos indesejáveis ao paciente.

ABSTRACT Objectives: This study sought to identify the physical and chemical incompatibilities among the drugs administered intravenously to patients admitted to an adult intensive care unit. We also aimed to establish pharmaceutical guidelines for administering incompatible drugs. Methods: This cross-sectional, prospective, and quantitative study was conducted from July to September 2015. Drug incompatibilities were identified based on an analysis of the patient prescriptions available in the hospital online management system. A pharmaceutical intervention was performed using the guidelines on the preparation and administration of incompatible drugs. Adherence to those guidelines was subsequently assessed among the nursing staff. Results: A total of 100 prescriptions were analyzed; 68 were incompatible with the intravenous drugs prescribed. A total of 271 drug incompatibilities were found, averaging 4.0 ± 3.3 incompatibilities per prescription. The most commonly found drug incompatibilities were between midazolam and hydrocortisone (8.9%), between cefepime and midazolam (5.2%), and between hydrocortisone and vancomycin (5.2%). The drugs most commonly involved in incompatibilities were midazolam, hydrocortisone, and vancomycin. The most common incompatibilities occurred when a drug was administered via continuous infusion and another was administered intermittently (50%). Of the 68 prescriptions that led to pharmaceutical guidelines, 45 (66.2%) were fully adhered to by the nursing staff. Conclusion: Patients under intensive care were subjected to a high rate of incompatibilities. Drug incompatibilities can be identified and eliminated by the pharmacist on the multidisciplinary team, thereby reducing undesirable effects among patients.

Farmacoepidemiología de los fármacos antagonistas de los receptores de angiotensina (ARA) II en el tratamiento de la hipertensión arterial esencial. méxico / Pharmacoepidemiology of antagonist receptors of the angiotensin (ARA) II in the treatment of essential hypertension. mexico

Epidemiología de la hipertensión arterial: A nivel mundial, se reporta que la prevalencia de hipertensión arterial en población adulta se encuentra entre un 20-27%. Tratamiento farmacológico: Los ARA II ejercen su acción a través del bloqueo de los receptores AT1 de la angiotensina II de forma específica y altamente selectiva y actúan inhibiendo los efectos clásicos desfavorables de angiotensina II. Así, los ARA II antagonizan la acción de la angiotensina II producida por cualquier vía enzimática y no actúan sobre la degradación de las quininas, por lo que no condicionan un aumento de sus niveles en sangre. Además, al bloquear los receptores ATI los ARA II permiten que la angiotensina II circulante se pueda ligar a los receptores AT2, lo que puede añadir un efecto adicional potencialmente muy beneficioso. Estudios de morbimortalidad en Hipertensión con ARA II: La eficacia de los ARA II para disminuir la tensión arterial está demostrada desde hace varios años, tanto en HTA leve como moderada o severa, y en múltiples estudios comparativos estos fármacos muestran una eficacia antihipertensiva similar a la de los IECAS, antagonistas del calcio o betabloqueantes. Por tanto, ante una eficacia antihipertensiva similar y un mejor perfil de tolerabilidad, los ARA II pueden considerarse una familia farmacológica de gran utilidad en el tratamiento actual de la HTA. Conclusiones: La conclusión de los autores de diversos estudios es que los IECA y los ARA-II tienen una efectividad antihipertensiva similar y los IECA, una peor tolerabilidad

Epidemiology of hypertension: Epidemiology of hypertension globally, it is reported that the prevalence of hypertension in adult population is between 20-27%. Pharmacotherapy: ARA II exert their action by blocking AT1 receptors Angiotensin II in a specific and highly selective and act by inhibiting the adverse effects angiotesin II classic. Thus, antagonize the action of angiotensin II produced by any means and do not act on enzymatic degradation of kinins, so do not condition an increase in blood levels. In addition to the ATI receptor blockade ARA II allow the circulating Angiotensin II may be linked to the AT2 receptor, which can add an additional potentially beneficial. Studies of morbidity and mortality in hypertension with ARA II: The efficacy of ARA II for lowering blood pressure is well established for several years, both in mild hypertension and moderate or severe and multiple studies comparing these drugs have shown similar antihypertensive efficacy to that of IECA inhibitors, calcium antagonists or beta-blockers. Therefore, given similar antihypertensive efficacy and better tolerability profile the ARA II may be considered a very useful drug family in the current treatment of hypertension. Conclusions: The conclusion of the authors of several studies is that IECA inhibitors and ARA II have similar antihypertensive effectiveness and IECA inhibitors, poorer tolerability

Spray drying of aqueous dispersions containing active ingredients for pharmaceutical purposes

The aim of this work was to prepare and characterize spray- dried pharmaceutical powders, and to optimize the variables of the spray drying [SD] process in order to obtain effective and stable drugs being released at the site of action. Two drugs were spray- dried, first bovine serum albumin [BSA], a protein model, was atomized in aqueous dispersions with ethyl cellulose [EC],second drug was sulfasalazine [SSZ] which atomized with eudragit [Eud] [gastro-resistant coating agent].Particle size distribution, shape and morphology, residual moisture, differential scanning calometry DSC thermograms, drug release profiles, yields, and encapsulation rate were studied. The best suitable conditions for the preparations of BSA were: solution feed rate of 4.38 ml/min, inlet temperature [Tin] of 160 C, outlet temperature [Tout] of 70 C, solid concentration content of 5.5%, and aspiration rate [Asp] of 80%.Microparticles [MP] produced by SD had spherical morphology but also there were disk- shaped particles of smooth surface with about 5 microm in dimension. The moisture content was 3.9%. BSA release profile in phosphate buffer showed sustained release, but almost perfect; 90% released after 8 hours, the yield of the process was about 69%,and the encapsulation efficiency [EE] was nearly 90%. The best conditions for the preparations of SSZ were: solution feed rate of 4.38 ml/min, inlet temperature [Tin] of 160 C, outlet temperature [Tout] of 80 C, solid concentration content of 2.8%, and aspiration rate of 80%. produced by SD had spherical morphology and there were some aggregations of smaller size, the particle median size was about 6.1 microm. The moisture content was 2.4%. SSZ release profile showed little drug release in the simulated stomach medium 15.9%after 2.5 hours, whereas it gave great release in the simulated intestine medium 93.1% for the same period of time. The yield of the process was about 65%, and the encapsulation efficiency [EE] was nearly 90%. These results confirmed that the spray drying methodology is an efficient, promising process for obtaining dried micro particles with specific and defined properties for pharmaceutical uses

Development and validation of a robust QSAR model for prediction of carcinogenicity of drugs.

Carcinogenicity is one of the toxicological endpoints causing the highest concern. Also, the standard bioassays in rodents used to assess the carcinogenic potential of chemicals and drugs are extremely long, costly and require the sacrifice of large numbers of animals. For these reasons, we have attempted development of a global quantitative structure–activity relationship (QSAR) model using a data set of 1464 compounds (the Galvez data set available from http://www.uv.es/~galvez/tablevi.pdf), including many marketed drugs for their carcinogenesis potential. Though experimental toxicity testing using animal models is unavoidable for new drug candidates at an advanced stage of drug development, yet the developed global QSAR model can in silico predict the carcinogenicity of new drug compounds to provide a tool for initial screening of new drug candidate molecules with reduced number of animal testing, money and time. Considering large number of data points with diverse structural features used for model development (ntraining = 732) and model validation (ntest = 732), the model developed in this study has an encouraging statistical quality (leave-one-out Q2 = 0.731, R2pred = 0.716). Our developed model suggests that higher lipophilicity values and conjugated ring systems, thioketo and nitro groups contribute positively towards drug carcinogenicity. On the contrary, tertiary and secondary nitrogens, phenolic, enolic and carboxylic OH fragments and presence of three-membered rings reduce the carcinogenicity. Branching, size and shape are found to be crucial factors for drug-induced carcinogenicity. One may consider all these points to reduce carcinogenic potential of the molecules.

Comparison of HPLC & spectrophotometric methods for estimation of antiretroviral drug content in pharmaceutical products.

Background & objectives: Simple and reliable methods to estimate drugs in pharmaceutical products are needed. In most cases, antiretroviral drug estimations are performed using a HPLC method, requiring expensive equipment and trained technicians. A relatively simple and accurate method to estimate antiretroviral drugs in pharmaceutical preparations is by spectrophotometric method, which is cheap and simple to use as compared to HPLC. We undertook this study to standardise methods for estimation of nevirapine (NVP), lamivudine (3TC) and stavudine (d4T) in single tablets/capsules by HPLC and spectrophotometry and to compare the content of these drugs determined by both these methods. Methods: Twenty tablets/capsules of NVP, 3TC and d4T each were analysed for their drug content by HPLC and spectrophotometric methods. Suitably diluted drug solutions were run on HPLC fitted with a C18 column using UV detection at ambient temperature. The absorbance of the diluted drug solutions were read in a spectrophotometer at 300, 285 and 270 nm for NVP, 3TC and d4T respectively. Pure powders of the drugs were used to prepare calibration standards of known drug concentrations, which was set up with each assay. Results: The inter-day variation (%) of standards for NVP, 3TC and d4T ranged from 2.5 to 6.7, 2.1 to 7.7 and 6.2 to 7.7, respectively by HPLC. The corresponding values by spectrophotometric method were 2.7 to 4.7, 4.2 to 7.2 and 3.8 to 6.0. The per cent variation between the HPLC and spectrophotometric methods ranged from 0.45 to 4.49 per cent, 0 to 4.98 per cent and 0.35 to 8.73 per cent for NVP, 3TC and d4T, respectively. Conclusions: The contents of NVP, 3TC and d4T in the tablets estimated by HPLC and spectrophotometric methods were similar, and the variation in the amount of these drugs estimated by HPLC and spectrophotometric methods was below 10 per cent. This suggests that the spectrophotometric method is as accurate as the HPLC method for estimation of NVP, 3TC and d4T in tablet/capsule. Hence laboratories that do not have HPLC equipment can also undertake these drug estimations using spectrophotometer.

Sucrose concentration and pH in liquid oral pediatric medicines of long-term use for children / Concentración de sacarosa y pH en medicamentos líquidos pediátricos para uso a largo plazo por vía oral

Objectives: To determine the pH and sucrose concentrations (SC) of pediatric liquid drugs of long-term use by children in order to evaluate the potential risk for dental caries and dental erosion. Methods: After assessing the pH, we analyzed 71 aqueous medicine samples for sucrose by the Lane-Eynon general volumetric method. The pH and SC values (mean ± standard deviation (SD) were calculated according to therapeutic action. Results: The highest and the lowest SC values (mean ± SD) were found in respiratory (37.75 percent ± 17.23 percent) and endocrine drugs (11.97 percent ± 15.16 percent) (p < 0.01). The values for medicines prescribed for daily ingestion were 47.15 percent ± 9.57 percent, whereas for twice daily and three or four times a day, these numbers were 24.42 percent ± 18.03 percent and 34.43 percent ± 14.83 percent, respectively (p < 0.01). The SC (mean ± SD)) values were higher in syrups (36.32 percent ± 17.62 percent) than in other formulations (p > 0.05). The overall pH (mean ± SD) was 5.89 ± 2.02 (range 2.3 ± 0.01 to 10.6 ± 0.02). In products with acidic pH, the SC (mean ± SD) was significantly lower (22.14 percent ± 15.72 percent) than in nonacidic medicines (39.22 percent ± 15.82 percent) (p < 0.001). Conclusions: It can be concluded that the pediatric medicines studied have a high SC and low pH, which vary according to therapeutic class, daily dose, and brand. Caution about dental caries, dental erosion, and systemic diseases such as diabetes mellitus is warranted when these medicines are ingested frequently.

Objetivos: Determinar el pH y las concentraciones de sacarosa de medicamentos pediátricos líquidos de uso oral a largo plazo, para evaluar el riesgo potencial de caries y erosión dental. Métodos: Se analizaron 71 muestras de medicamentos líquidos; después de evaluar el pH, se determinó la sacarosa por el método volumétrico de Lane&Eynon. El pH y los valores de sacarosa (media ± desviación estándar [DE]) se calcularon de acuerdo con la acción terapéutica. Resultados: El valor de sacarosa más alto (media ± DE) se encontró en los medicamentos respiratorios (37,75 por ciento ± 17,23 por ciento) y el más bajo en los endocrinos (11,97 por ciento 15,16 por ciento ±) (p < 0,01). Los medicamentos recetados para ingerir una vez al día tuvieron valores de 47,15 por ciento ± 9,57 por ciento; los que se administran dos veces al día, 24,42 por ciento ± 18,03 por ciento, y los recetados tres o cuatro veces al día, 34,43 por ciento ± 14,83 por ciento (p < 0,01). Los valores de sacarosa fueron mayores en jarabes (36,32 por ciento ± 17,62 por ciento) que en otras formas farmacéuticas (p > 0,05). El pH general fue 5,89 ± 2,02 (recorrido 2,3 ± 0,01 a 10,6 ± 0,02). La sacarosa fue significativamente inferior en los productos con el pH ácido (22,14 por ciento ± 15,72 por ciento) que en los medicamentos no ácidos (39,22 por ciento ± 15,82 por ciento) (p < 0,001). Conclusiones: Los medicamentos pediátricos estudiados tienen una concentración de sacarosa alta y un pH bajo, los cuales varían según la clase terapéutica, la dosis diaria y la marca. Cuando estos medicamentos se ingieren con frecuencia, se debe tener cuidado con la caries y la erosión dental, así como con las enfermedades sistémicas como la diabetes mellitus.

Estudo de compatibilidade fármaco/excipiente e de estabilidade do prednicarbato por meio de técnicas termoanalíticas, e encapsulação do fármaco em sílica mesoporosa do tipo SBA-15 / Compatibility drug/excipient and stability studies of prednicarbate by thermal analysis, and loading of drug in mesoporous silica type SBA-15

Nos últimos 30 anos, a incidência da dermatite atópica aumentou de 4 para 12% em toda população mundial, acarretando um aumento significativo nos custos envolvidos no seu tratamento, tanto para as famílias, quanto para os sistemas de saúde. Para a dermatite atópica que ocorre de maneira suave à moderada, os corticosteróides de uso tópico são usualmente utilizados. Dentre eles, o prednicarbato se destaca por ser um potente agente antiinflamatório e por ter um baixo potencial em causar atrofia de pele. Neste trabalho, inúmeras técnicas de análise e de caracterização, em especial as técnicas de DSC e TG, foram utilizadas para auxiliar no desenvolvimento racional de uma formulação farmacêutica semi-sólida de uso tópico contendo o prednicarbato como ingrediente ativo. Diversas aplicações da análise térmica voltada à tecnologia farmacêutica foram apresentadas. A estrutura química do produto sólido intermediário originado na primeira etapa do processo de decomposição térmica do prednicarbato foi determinada a partir da associação dos resultados termoanalíticos àqueles obtidos pelas técnicas de RMN, CLAE-EM/EM e espectroscopia de absorção na região do infravermelho. Avaliando-se os resultados, foi possível correlacionar à etapa de decomposição térmica do fármaco com a eliminação do grupo químico carbonato ligado ao seu C17. As curvas TG/DTG das misturas físicas 1:1 entre o prednicarbato e os excipientes álcool estearílico e estearato de glicerila mostraram uma redução da temperatura em que o processo de decomposição térmica do fármaco se inicia (Tonset TG), enquanto que para a mistura prednicarbato/pirrolidona carboxilato sódio, a presença do excipiente pouco interferiu no início do processo ( ΔTMáx dm / dt=0 DTG = 3 ºC), mas originou um aumento da taxa de decomposição (ΔTpico DTG = 35 ºC). A alteração da estabilidade térmica do prednicarbato evidenciada no estudo de compatibilidade com o excipiente estearato de glicerila foi também observada na avaliação da Ea...

In the last 30 years the incidence of atopic dermatitis increased from 4 to 12% around the world, resulting in a significant increase in costs involved to its treatment, both for families and for health systems. For atopic dermatitis that occurs on a weak to moderate way, the topical corticosteroids are frequently used. Among them, the prednicarbate has special attention due to its potent anti-inflammatory activity and due to its low potential in causing skin atrophy. In this work, several analytical and characterization techniques, especially the DSC and TG, were used to assist in the rational development of a semi-solid pharmaceutical formulation for topical use containing prednicarbate as active ingredient. A lot of applications of thermal analysis focused on pharmaceutical technology were presented. The elucidation of chemical structure of the solid product formed at the first thermal decomposition step of the prednicarbate was performed using the thermoanalytical results and results obtained by NMR, HPLC-MS/MS and infrared spectroscopy. Assessing the results, it was possible to correlate the thermal decomposition step of prednicarbate with to elimination of carbonate group bonding to its C17, and subsequent formation of double-bond between C17 and C16. The TG/DTG curves of the binaries mixtures between the drug and stearyl alcohol and glyceryl stearate showed a significant change in the first thermal decomposition step of prednicarbate. For the 1:1 physical mixture between prednicarbate and sodium pirrolidone carboxylate, the TG/DTG curves showed an increase in the thermal decomposition rate of the drug (ΔTpico DTG = 35 ºC), but the presence of pirrolidone almost did not interfere at the beginning of this first thermal decomposition stage (ΔTMáx dm / dt=0 DTG = 3 ºC). The change of thermal stability of prednicarbate observed in the compatibility study with glyceryl stearate excipient was also observed during the evaluation of Ea value of this...

Sensitive and rapid titrimetric and spectrophotometric methods for the determination of stavudine in pharmaceuticals using bromate-bromide and three dyes

Four sensitive and rapid methods for the determination of stavudine (STV) in bulk drug and in dosage forms were developed and optimized. In titrimetry, aqueous solution of STV was treated with a known excess of bromate-bromide in HCl medium followed by estimation of unreacted bromine by iodometric back titration. Spectrophotometric methods involve the addition of a measured excess of bromate-bromide in HCl medium and subsequent estimation of the residual bromine by reacting with a fixed amount of methyl orange, indigocarmine or thymol blue followed by measurement of absorbance at 520 nm (method A), 610 nm (method B) or 550 nm (method C). In all the methods, the amount of bromate reacted corresponds to the amount of STV. Calculations in titrimetry were based on a 1:0.666 (STV:KBrO3) stoichiometry and the method was found to be applicable over 3.5-10 mg range. A linear increase in absorbance with concentration of STV was observed in the spectrophotometric methods, and the Beer's law was obeyed over the concentration ranges 0.125-1.75, 1-10 and 1-9.0 µg mL-1 STV for method A, method B and method C, respectively. The methods when applied to the determination of STV in tablets and capsules were found to give satisfactory results.

Este trabalho descreve quatro métodos rápidos e sensíveispara a determinação de estavudina (STV) na matéria-prima ou em produtos formulados. Soluções aquosas de STV podem ser tituladas tratando-as com excesso de bromato-brometo em meio ácido clorídrico, seguido da determinação iodimétrica de bromo em excesso. Métodos espectrofotométricos tambémenvolvem a adição de excesso de bromato-brometo à amostra, seguida da determinação de bromo residual por adição de uma quantidade fixa de alaranjado de metila, índigo-carmim ou azul de timol, e de medidas de absorbância nos comprimentos de onda apropriados: 520, 610 ou 550 nm. Em todos os métodos, a quantidade de bromato consumida corresponde à quantidade de STV e os resultados da sua aplicação à determinação de STV em comprimidos e cápsulas são satisfatórios.

Strong and weak hydrogen bonds in drug-DNA complexes: a statistical analysis.

A statistical analysis of strong and weak hydrogen bonds in the minor groove of DNA was carried out for a set of 70 drug-DNA complexes. The terms 'strong' and 'weak' pertain to the inherent strengths and weakness of the donor and acceptor fragments rather than to any energy considerations. The dataset was extracted from the protein data bank (PDB). The analysis was performed with an in-house software, hydrogen bond analysis tool (HBAT). In addition to strong hydrogen bonds such as O-H...O and N-H...O, the ubiquitous presence of weak hydrogen bonds such as C-H...O is implicated in molecular recognition. On an average, there are 1.4 weak hydrogen bonds for every strong hydrogen bond. For both categories of interaction, the N3 of purine and the O2 of pyrimidine are favoured acceptors. Donor multifurcation is common with the donors generally present in the drug molecules, and shared by hydrogen bond acceptors in the minor groove. Bifurcation and trifurcation are most commonly observed. The metrics for strong hydrogen bonds are consistent with established trends. The geometries are variable for weak hydrogen bonds. A database of recognition geometries for 26 literature amidinium-based inhibitors of Human African Trypanosomes (HAT) was generated with a docking study using seven inhibitors which occur in published crystal structures included in the list of 70 complexes mentioned above, and 19 inhibitors for which the drug-DNA complex crystal structures are unknown. The virtual geometries so generated correlate well with published activities for these 26 inhibitors, justifying our assumption that strong and weak hydrogen bonds are optimized in the active site.

Excipientes de medicamentos e as informações da bula / Pharmaceutical excipients and the information on drug labels

OBJETIVO: Avaliar a presença de conservantes, corantes, adoçantes e aromatizantes em 73 apresentações farmacêuticas de 35 medicamentos para uso oral, e as informações da bula sobre excipientes. MÉTODOS: Selecionamos 35 medicamentos, de venda livre ou sob prescrição médica, comercializados no Brasil. A amostra incluiu: analgésicos/antitérmicos, antimicrobianos, mucolíticos, antitussígenos, descongestionantes, anti-histamínicos, broncodilatadores, corticosteróides, antiinflamatórios e suplementos vitamínicos. Foram analisadas 73 apresentações desses fármacos, anotando-se as informações da bula sobre conservantes, corantes, adoçantes e aromatizantes. RESULTADOS: A bula de um medicamento (1,3 por cento) não mencionava os ingredientes inativos. Os conservantes mais encontrados nos medicamentos foram metilparabeno e propilparabeno (43 por cento e 35,6 por cento respectivamente). Os adoçantes mais usados foram: sacarose (açúcar) (53,4 por cento), sacarina sódica (38,3 por cento) e sorbitol (36,9 por cento). Vinte e um produtos (28,7 por cento) continham dois adoçantes. Predominaram os medicamentos sem corante (43,8 por cento), seguidos pelos coloridos por amarelo crepúsculo (amarelo FD&C no. 6) (15 por cento). Cinco produtos (6,8 por cento) continham mais de um corante. A tartrazina (amarelo FD&C no. 5) foi encontrada em sete formulações (9,5 por cento). Os aromatizantes mais usados foram os de frutas (83 por cento). Constatamos a freqüente omissão das bulas sobre o teor exato de açúcar dos produtos (77 por cento). Duas das quatro bulas de medicamentos contendo aspartame não mencionavam as precauções no uso por fenilcetonúricos. CONCLUSÕES: A omissão e a imprecisão das informações da bula sobre os excipientes farmacêuticos expõem os indivíduos suscetíveis ao risco de reações adversas dos conservantes e corantes. Também podem ocorrer complicações do uso inadvertido de medicamentos contendo açúcar pelos pacientes diabéticos, ou de fármacos adoçados com aspartame pelos fenilcetonúricos.

AIM: to evaluate the presence of preservatives, dyes, sweeteners and flavouring substances in 73 pharmaceutical preparations of 35 medicines for oral administration, according to drug labeling information about the excipients. METHODS: 35 medications were selected, both over-the-counter and prescription durgs, marketed in Brazil. The sample included: analgesic/antipyretic, antimicrobial, mucoregulatory, cough and cold, decongestant, antihistamine, bronchodilator, corticosteroid, antiinflammatory and vitamin medications. We collected data on 73 preparations of these drugs, according to drug labeling information regarding preservatives, dyes, sweeteners and flavourings. RESULTS: Methylparaben and propylparaben were the most common preservatives found (43 percent and 35.6 percent respectively). The most common sweeteners were: sucrose (sugar) (53.4 percent), sodium saccharin (38.3 percent) and sorbitol (36.9 percent). Twenty-one medicines (28,7 percent) contained two sweeteners. Colourless medicines predominated (43.8 percent), followed by those with sunset yellow dye (FD&C yellow no. 6) (15 percent). Five products (6.8 percent) contained more than one colour agent. Tartrazine (FD&C yellow no. 5) was present in seven preparations (9.5 percent). Fruit was the most common flavouring found (83 percent). Labelings of drugs which contained sugar frequently omitted its exact concentration (77 percent). Of the four labelings of medicines which contained aspartame, two did not warn patients regarding phenylketonuria. CONCLUSION: Omission and inacuracy of drug labeling information on pharmaceutical excipients may expose susceptible individuals to adverse reactions caused by preservatives and dyes. Complications of inadvertent intake of sugar-containing medicines by diabetics, or aspartame intake by patients with phenylketonuria may also occur.

Comportamento térmico de alguns fármacos e medicamentos / Thermal studies of some pharmaceutical drugs

A técnica de análise térmica apresenta aplicações em diversos ramos da ciência, entre eles a indústria farmacêutica, a qual pode utilizá-la para caracterização e estudo das matérias primas e produtos finais. Os compostos farmacêuticos apresentam diferentes formas morfológicas ou estruturais,que afetam diretamente na sua estabilidade, ação e liberação. O desenvolvimento e fabricação de medicamentos requerem intenso cuidado devido a pureza, qualidade e estabilidade dos componentes. Um dos itens para se obter uma formulação estável e efetiva depende dos cuidados na escolha dos excipientes utilizados, onde uma de suas propriedades é a de interferir na biodisponibilidade e proteção do fármaco frente a degradação. Neste trabalho foram utilizadas técnicas de análise térmica (TG/DTG/DSC/DTA) e a espectroscopia Raman para estudar possíveis interações entre o fármaco e seus excipientes. Foram selecionados para o estudo os medicamentos Aspirina® e AAS®, comparados com o seu princípio ativo ácido acetil salicílico. As amostras não sofreram pré tratamento e foram analisadas como adquiridas no mercado. Os resultados obtidos através das técnicas de análise térmica evidenciaram uma possível interação entre os diferentes excipientes utilizados e o princípio ativo. Os espectros Raman corroboram com os resultados obtidos das análises térmicas dos medicamentos. Através dos resultados obtidos concluímos que as diferentes composições existentes na formulação dos medicamentos podem promover mudanças em suas propriedades físicas e consequentemente na sua atividade biológica.

Quantitative determination of ciprofloxacin and norfloxacin in pharmaceutical preparations by high performance liquid chromatography

The objetive of the research was to develop and validate an analytical method for quantitative determination of ciprofloxacin (CIP) and norfloxacin (NOR) in pharmaceutical preparations. A simple and rapid chromatographic method was developed and validated for quantitative determination of two fluoroquinolone antibiotics in tablets and injection preparations. The quinolones were analyzed by using a LiChrospher® 100 RP-18 column (5 µm, 125 x 4 mm) and a mobile phase consisted of water:acetronitrile:triethylamine (80:20:0.3 v/v/v). The pH of final mixture was adjusted to 3.3 with phosphoric acid. The flow rate was 1.0 mL/min and UV detection was made at 279nm. The analyses were performed at room temperature (24 ± 2°C). CIP and NOR were eluted within 5 min. The calibration curves were linear (r > 0.9999) over a concentration range from 4.0 to 24.0 µg/mL. The relative standard deviation (RSD) was < 1.0 percent and the mean recovery was 101.85 percent...

Formulation and in vitro evaluation of theophylline-Eudragit® sustained-release tablets

Tablets containing theophylline (66.67 porcento) based on a Eudragit® RS 30D and NE 30D matrices containing 10 porcento to 30 porcento of either of the polymer were produced by compression method. The influence of the different proportions of methacrylic esters, the use of lactose and tribasic calcium phosphate as diluents and also the effects of the addition of magnesium stearate as a hydrophobic agent lubricant on the theophylline release, were studied. Physicochemical analyses and drug content was evaluated. In vitro drug release studies were carried out in simulated gastric fluid without pepsin (pH1.2) and simulated intestinal fluid without pancreatin (pH7.5)...

Enhancement of gastrointestinal absorption of poorly water soluble drugs via lipid based systems.

Development of knowledge on lipids has attracted the scientific community for the effective utilization of the natural and synthetic lipids. Bioavailability of poorly water soluble drugs from gastrointestinal tract (GIT) can be enhanced by formulating the drugs in lipid based formulations. This formulation can increase the dissolution of poorly water soluble drugs, and facilitates the formation of solubilized phases from which absorption may occur. The enhanced solubility of lipophilic drugs from lipid-based systems will not necessarily arise directly from the administered lipid, but most likely from the intra luminal processing to which they are subjected prior to absorption. This review will focus on assessment of lipid-based formulations of drugs with a consideration of how gastrointestinal physiology, the choice of lipids and their formulation attribute and the mode of lipid digestion in the GIT influence the bioavailability of lipophilic drugs.

A centralidade do medicamento na terapêutica contemporânea / The drug centrally in contemporary therapeutic

Medicamentos de base química assinalaram uma revolução nas atividades de saúde pública e no exercício da medicina, alcançaram um lugar hegemônico na terapêutica contemporânea e, simbolicamente, ultrapassaram as fronteiras do que se entende como um mero recurso terapêutico. Na atualidade, são consumidos cada vez amis com o objetivo de moldar o corpo ou o comportamento a padrões estéticos e de conduta rigidamente estabelecidos na cultura contemporânea. A análise de 237 reportagens veiculadas nas décadas de oitenta e noventa, em jornais e revistas de larga circulação sobre alguns dos medicamentos da grande indústria farmacêutica mais vendidos no país, demonstrou uma tendência ao despregamento do consumo de medicamentos da cultura médica, sustentada na automedicação com resposabilização por seus riscos. Nestas reportagens, o discurso que favorece o consumo de medicamentos se caracterizou pela associação de informações de origem científica a símbolos de poder, beleza, juventude e de força, sustendados em e ao mesmo tempo reforçando valores dominantes na cultura atual, tais como o individualismo, a competição acirrada e o consumismo. A abordagem de riscos prevaleceu em 55 por cento do conjunto de reportagens, em discurso acentuando a autonomia e a responsabilização do indivíduo no consumo de medicamentos e seus riscos. O apelo a padrões dominantes de estética e de conduta conjugado à crescente divulgação dos riscos tende a deslocar o medicamento do campo de cura e de saúde para o de controle de risco, enquanto intervenção que evoca noções do certo-incerto, dentro-fora, corpo-espírito, vida-morte. Desta perspectiva, o medicamento químico, como defesa mágica materializada pela ciência e tecnologia, ao mesmo tempo em que expressa o poder de cura de agentes da medicina hegemônica, seu projeto terapêutico e seu aparato tecnológico, constitui-se crescentemente em objeto de desconfiança na ciência e no modelo linear de progresso que projeta a utopia de controle e reconstrução da natureza através da biotecnologia. A diversificação de sentidos e práticas em saúde, portadores de diferentes valores relativos à própria vida em sociedade, pode estar sinalizando um deslocamento na centralidade do medicamento na terapêutica e na cultura. A busca de bem estar tende a valorizar um processo interior, individual e coletivo, relacionado à transformação de nosso jeito de sentir, ser e viver, dando lugar a uma nova sabedoria e uma nova ética social do bem viver. Biomedicina

Análise químico-farmacêutica da oxamniquina e de suas especialidades farmacêuticas / Chemical pharmaceutical analysis of oxamniquine and its pharmaceutical specialities

Este trabalho foi desenvolvido para análise da oxamniquina matéria-prima e para a elaboração de metodologias no controle de qualidade de suas especialidades farmacêuticas, supensão e cápsulas, especialmente em atenção à introdução da classe dos genéricos e possíveis similares. Foram realizados testes de caracterização, identificação e doseamento tanto para matéria-prima como para as formas faramcêuticas. Os resultados dos testes de caracterização mostraram-se estar de acordo com a literatura. A determinação qualitativa da oxamniquina nas amostras foi realizada por identificação de grupos funcionais da molécula e usando técnicas instrumentais. O doseamento da matéria-prima foi realizado por espectrofotometria...

Estudo comparativo "in vitro" das propriedades biofarmacotécnicas de comprimidos de cloridrato de metformina comercializados no Brasil / In vitro comparative study of biopharmaceutics properties of metformin hydrochloride tablets marketed in Brazil

Comprimidos de cloridrato de metformina de 850 mg, dos laboratórios A e B (3 lotes de cada), foram submetidos a ensaios físicos e físico-químicos conforme recomendações da Farmacopéia Britânica (1993). O fármaco foi quantificado por espectrofotometria na região UV a 233nm. Os resultados indicaram que dois lotes do laboratório B estavam em desacordo com as especificações por apresentarem dureza de 2,57ñ0,98 e 2,89ñ0,62 kgf, inferior ao mínimo exigido pela Farmacopéia Brasileira 4ª ed.(parte I), que é de 3 kgf. Todos os lotes do laboratório A mostravam camada de revestimento, dureza bastante irregular (D=22,99ñ1,49, 8,64ñ0,99 e 19,02ñ2,36) e teor de fármaco, aproximadamente, 22 porcento abaixo...