Surface Degradation of Resin-based Materials by Pediatric Syrup Containing Amoxicillin under Erosive Challenge

Objective: To investigate the effect of a pediatric syrup containing Amoxicillin on resin-based on the surfaces of resin-based materials under pH cycling. Material and Methods: Cylindrical samples (n=60) of a compomer (Freedom) and a microhybrid composite (TPH Spectrum) were prepared following the manufacturer's instructions. The specimens were divided into two groups and treated for 30min, twice a day, for 14 days with a pediatric syrup containing Amoxicillin, Amoxil™ 500mg/5ml (experimental group) or Distilled water (control group). During the 14 days, the samples were submitted to pH cycling (3h in demineralizing, 20h in remineralizing saliva, and 1h for treatment). The surface roughness was evaluated at baseline, on the 7th and 14th days of erosive challenge using a profilometer and illustrated by SEM. The data were statistically analyzed by one-way ANOVA, Tukey HSD and paired T- tests (p < 0.05). At baseline, the mean Ra TPH = mean Ra F (p > 0.05). Results: After 7 days, it was observed no erosion (p = 0.674) for THP Spectrum (0.19 Ra) and an increasing of Ra (p = 0.02) for Freedom (19.95 Ra). After 14 days, it was observed an increasing of Ra for both THP Spectrum (0.56 Ra) and for Freedom (3.44 Ra), demonstrating that the degradation was treatment and time-dependent (p < 0.001). The pediatric syrup containing Amoxicillin increased the surface roughness of the TPH Spectrum surface one and a half times (p = 0.003) and the surface roughness of Freedom was increased by more than two times (p < 0.001). SEM images showed different aspects of the surfaces of the two materials with a loss of integrity to both. Conclusion: The pediatric syrup containing Amoxicillin under pH cycling increased the roughness of the both tested resin-based restorative materials.

Influence of vascular endothelial growth factor inhibition on simple renal cysts in patients receiving bevacizumab-based chemotherapy

PURPOSE: Although angiogenesis has been implicated in the promotion of renal cyst growth in autosomal dominant polycystic kidney disease, no studies have investigated the role of angiogenesis in the growth of simple renal cysts. The aim of current study was to investigate the effect of chemotherapy with the antivascular endothelial growth factor antibody bevacizumab on renal cyst development and growth in cancer patients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 136 patients with a variety of cancers that were treated with bevacizumab-based chemotherapy for metastatic disease. The presence of and changes in renal cysts were evaluated by retrospective analysis of computed tomography scans performed for assessment of tumor response to bevacizumab-based therapy. RESULTS: The median age of the patients was 64 years. Renal cysts were identified in 66 patients, in whom 33 (50%) had a single cyst and the rest had 2 or more cysts. The average dose of bevacizumab was 2.68 mg/kg per week. Median duration of treatment was 33 weeks. Average cyst size was 1.9±2.4 cm at the beginning of the study and the majority of the cysts (54 patients, 84%) did not change in size or shape during bevacizumab treatment. No patients were identified with new cysts. Cyst size changed in 10 patients (16%): an increase of 15% to 40% from the baseline size in 5 patients and a decrease in size of 10% to 70% in another 5 patients. The duration of bevacizumab therapy was significantly longer in the subgroup of patients with diminished or increased cyst size than in the patients with stable cyst size: 62 weeks versus 29 weeks, respectively (p=0.0002). CONCLUSIONS: Our data demonstrated that simple renal cysts were stable in size and number in the vast majority of cancer patients treated with bevacizumab.

Antibiotic prophylaxis with intravenous ceftriaxone and fluoroquinolone reduces infectious complications after transrectal ultrasound-guided prostatic biopsy

PURPOSE: To assess the rates of infectious complications before and after the change of prophylactic antibiotic regimens in prostate needle biopsy. MATERIALS AND METHODS: The records of 5,577 patients who underwent prostate needle biopsy at Asan Medical Center between August 2005 and July 2012 were retrospectively reviewed. Group 1 (n=1,743) included patients treated between 2005 and 2009 with fluoroquinolone for 3 days, group 2 (n=2,723) included those treated between 2009 and 2012 with ceftriaxone once before the biopsy and fluoroquinolone before biopsy and continue therapy for 3 days, and group 3 (n=1,111) received the same treatment for more than 7 days after the biopsy. Univariable and multivariable logistic regression models addressed risk factors associated with infectious complication after prostate needle biopsy. RESULTS: Infectious complication after prostate needle biopsy developed in 18 (group 1), seven (group 2), and two patients (group 3) (p=0.001). In group 1, seven patients with infectious complication had positive blood cultures and harbored fluoroquinolone-resistant Escherichia coli, four had ceftriaxone susceptible isolates, and three had extended spectrum beta-lactamase-positive E. coli. Two patients in group 1 required intensive care because of septic shock. In multivariable analysis, the patients with combination of fluoroquinolone and ceftriaxone had significantly lower infectious complication rate than the fluoroquinolon alone (p=0.003). CONCLUSIONS: Antibiotic prophylaxis with ceftriaxone and fluoroquinolone before prostate needle biopsy decreased the risk of potentially serious infectious complications.

Evaluación farmacoterapéutica y evolutiva de uveítis crónicas y recurrentes no infecciosas / Pharmacological treatment evaluation and progression of non-infectious recurrent and chronic uveitis

OBJETIVOS: evaluar el tratamiento farmacológico e identificar los factores pronósticos en una evolución clínica desfavorable con uveítis crónicas y recurrentes no infecciosas, en el Instituto Cubano Oftalmología "Ramón Pando Ferrer" durante el período 2012-2013. MÉTODOS: se realizó un estudio de utilización de medicamentos. Se efectuó un diseño de cohorte retrospectivo evaluativo y un estudio transversal analítico de factores pronósticos. Fueron evaluados 116 pacientes. Las variables utilizadas correspondieron a la evaluación farmacoterapéutica: selección del medicamento, pauta de administración y causas de incumplimiento terapéutico. Para la evolución clínica desfavorable se analizaron variables sociodemográficas y clínicas. Se calcularon frecuencias absolutas y relativas. Se realizó un análisis univariado. Las variables significativas a la evolución se incluyeron en el modelo de regresión logística múltiple. RESULTADOS: no existieron errores en la prescripción en el 100 % de los evaluados. El 15,5 % de los pacientes no cumplieron con el tratamiento prescrito; 83,3 % se relacionó con la presencia de reacciones adversas y 33,3 % con la falta de disponibilidad. El 57 % presentó efectos adversos por corticoesteroides y el 39 % por inmunosupresores. El curso clínico crónico y la localización resultaron factores influyentes en una evolución desfavorable. CONCLUSIONES: la evaluación farmacoterapéutica en el caso de las uveítis crónicas es adecuada. No existen errores en la prescripción. Las causas más frecuentes de incumplimiento terapéutico son la suspensión del tratamiento por efectos adversos, la falta de disponibilidad de inmunosupresores y la alternativa biológica. El curso clínico crónico y la localización de las uveítis pueden considerarse como un factor pronóstico en la evolución desfavorable de esta enfermedad.

OBJECTIVES: to evaluate the pharmacological treatment and to identify the predictive factors in unfavorable clinical progression of patients with non-infectious recurrent and chronic uveitis at "Ramon Pando Ferrer" Cuban Institute of Ophthalmology in the period of 2012 to 2013. METHODS: drug use study was conducted based on a design of retrospective evaluative cohort and a cross-sectional analytical study of predictive factors. One hundred and sixteen patients were evaluated. The variables corresponded to the pharmacological treatment evaluation: selection of drug, administration guidelines and causes of non-adherence to treatment. For the unfavorable clinical progression, the sociodemographic and clinical variables were considered. Absolute and relative frequencies were calculated; the univariate analysis was made and the significant variables for progression were included in the multiple logistic regression model. RESULTS: there was no error in prescribing 100 % of the evaluated cases. In the group, 15,5 % of patients did not adhere to the prescribed treatment; 83,3 % due to adverse reactions and 33,3 % to lack of drug availability. Fifty seven percent suffered adverse effects from corticosteroids and 39% from immunosupressors. The chronic clinical course and the location were the most influential factors in the unfavorable progression. CONCLUSIONS: the pharmacological treatment evaluation for the chronic uveitis is adequate. There are no errors in prescription. The most frequent causes of non-adherence to treatment are cessation of treatment on account of adverse effects, lack of availability of immunosupressors and biological alternative. The chronic clinical course and the location of uveitis can be considered as predictive factors in the unfavorable progression of the disease.

Anticuerpo monoclonal humanizado itolizumab (anti-cd6) en síndromes linfoproliferativos cd 6+. Experiencia preliminar / Itolizumab humanized monoclonal antibody (anti-cd6) in patients with cd6+ lymphoproliferative disorders. Preliminary experience

Introducción: la molécula CD6 es una glicoproteína de membrana considerada un antígeno de diferenciación leucocitario. El anticuerpo monoclonal humanizado itolizumab (anti-CD6) reconoce la molécula CD6 humana en las células mononucleares periféricas malignas de pacientes con leucemia linfocítica crónica- B y en los linfocitos de lesiones cutáneas de pacientes con linfoma T cutáneo. Objetivo: exponer los resultados preliminares de tres pacientes con leucemia linfocítica crónica-B tratados con el itolizumab, con dosis de 0.8 mg/kg/dosis semanal por 12 semanas. Métodos: la evaluación de la toxicidad asociada a la administración del itolizumab se realizó según Common Terminology Criteria for Adverse Events, versión 3.0, y la evaluación del beneficio clínico se definió según los criterios de respuesta, previamente establecidos por el National Cancer Institute Work Group, en remisión completa, remisión parcial, enfermedad estable, progresión y recaída. La evaluación de la respuesta se realizó después de haber recibido 6 administraciones del itolizumab (semana 7), después de haber recibido las 12 administraciones del itolizumab (semana 13), 6 semanas después de la última dosis (semana 18) y 12 semanas después de la última dosis (semana 24). Los datos de cada paciente se recogieron en las historias clínicas. Resultados: se evaluó la seguridad de la administración del producto en pacientes con síndromes linfoproliferativos CD6+ y se obtuvieron evidencias preliminares del efecto terapéutico de dicho fármaco. Conclusiones: en el 100 por ciento de los pacientes incluidos se reportó la aparición de fiebre y escalofríos relacionados con la primera infusión. No se observaron efectos adversos serios. Todos los pacientes evaluados tuvieron al menos alguna mejoría clínica o hematológica...

CD6 molecule is a membrane glycoprotein considered a leukocyte differentiation antigen. Itolizumab, humanized monoclonal antibody (anti-CD6) recognizes the human CD6 molecule in malignant peripheral mononuclear cells of patients with B-cell chronic lymphocytic leukemia and in lymphocytes of cutaneous lesions in patients with cutaneous T- cell lymphoma. We describe preliminary results of 3 patients with B-cell chronic lymphocytic leukemia treated with itolizumab at a weekly dose of 0.8mg/kg/dose for 12 weeks. Product administration safety was evaluated in patients with CD6+ lymphoproliferative disorders and preliminary evidence of therapeutic effect of the drug was obtained. In 100 percent of the patients the onset of fever and chills associated to the first infusion were reported. No serious adverse effects were observed. All patients evaluated had at least some clinical or hematological improvement...

Assessment of the quality of compounded fluconazole capsules marketed in the region of Araraquara (SP, Brazil) / Avaliação da qualidade de cápsulas de fluconazol manipuladas comercializadas na região de Araraquara (SP, Brasil)

O controle de qualidade de fármacos desempenha um papel importante na saúde pública ao garantir segurança e eficácia de medicamentos. No sistema de saúde pública,as farmácias magistrais também são importantes. Elas fornecem medicamentos personalizados como produtos dermatológicos e doses específicas para crianças.Infelizmente, muitos casos de produtos magistrais fabricados fora do padrão mínimo de qualidade têm sido relatados no Brasil. Neste trabalho, a qualidade das cápsulas magistrais de fluconazol 150 mg foi avaliada e os resultados foram comparados com os valores recomendados pela Farmacopeia Brasileira. Os resultados sugerem que é possível manipular produtos que satisfaçam as especificações farmacopeicas, mas estes ainda mostram que há farmácias magistrais onde o controle de qualidade é deficiente ou inexistente. O fluconazol é um fármaco importante no tratamento de infecções fúngicas. Seu uso como forma farmacêutica manipulada sem elevados padrões de qualidade é fortemente relacionado com a falha terapêutica e intoxicações, assim como o surgimento de microorganismos resistentes. Portanto, a necessidade de melhoria dos processos nas farmácias magistrais se torna mais enfático. Existem métodos validados que podem ser utilizados com sucesso para a análise de rotina de controle de qualidade e que podem ser implementados por qualquer farmácia de manipulação...

The quality control of drugs has an important role in public health, in ensuring the efficacy and safety of medicines. In the public health system, compounding pharmacies play a vital part. They provide medicines tailored to the individual patient, for example dermatological products and specific doses for children. Unfortunately, many cases of compounded products falling below the minimum quality standard have been reported in Brazil. In this study, the quality of compounded 150 mg fluconazole capsules was assessed and the results were compared with values stipulated in the Brazilian pharmacopoeia. The results suggest that, while it is certainly possible to prepare products meeting pharmacopoeial specifications, there are pharmacies where the quality control is deficient or nonexistent. Fluconazole is an important drug in combatting fungal infections. The use of fluconazole in dosage forms manufactured without high standards of quality control is strongly linked to treatment failure and cases of intoxication, as well as the emergence of resistant microorganisms. This highlights the urgent need for process improvement in compounding pharmacies. There are validated methods that can be successfully employed for routine quality control analysis that can be implemented by any compounding pharmacy...

Prophylactic Phenylephrine for Iatrogenic Priapism: A Pilot Study With Peyronie's Patients

PURPOSE: Although penile duplex Doppler ultrasonography (PDDU) is a common and integral procedure in a Peyronie's disease workup, the intracavernosal injection of vasoactive agents can carry a serious risk of priapism. Risk factors include young age, good baseline erectile function, and no coronary artery disease. In addition, patients with Peyronie's disease undergoing PDDU in an outpatient setting are at increased risk given the inability to predict optimal dosing. The present study was conducted to provide support for a standard protocol of early administration of phenylephrine in patients with a sustained erection after diagnostic intracavernosal injection of vasoactive agents to prevent the deleterious effects of iatrogenic priapism. MATERIALS AND METHODS: This was a retrospective review of Peyronie's disease patients who received phenylephrine reversal after intracavernosal alprostadil (prostaglandin E1) administration to look at the priapism rate. Safety was determined on the basis of adverse events reported by subjects and efficacy was determined on the basis of the rate of priapism following intervention. RESULTS: Patients with Peyronie's disease only had better hemodynamic values on PDDU than did patients with Peyronie's disease and erectile dysfunction. All of the patients receiving prophylactic phenylephrine had complete detumescence of erections without adverse events, including no priapism cases. CONCLUSIONS: The reversal of erections with phenylephrine after intracavernosal injections of alprostadil to prevent iatrogenic priapism can be effective without increased adverse effects.

Efficacy, Tolerability, and Safety of Oxybutynin Chloride in Pediatric Neurogenic Bladder With Spinal Dysraphism: A Retrospective, Multicenter, Observational Study

PURPOSE: Anticholinergics are a key element in treating neurogenic detrusor overactivity, but only limited data are available in the pediatric population, thus limiting the application to children even for oxybutynin chloride (OC), a prototype drug. This retrospective study was designed to provide data regarding the efficacy, tolerability, and safety of OC in the pediatric population (0-15 years old) with spinal dysraphism (SD). MATERIALS AND METHODS: Records relevant to OC use for neurogenic bladder were gathered and scrutinized from four specialized clinics for pediatric urology. The primary efficacy outcomes were maximal cystometric capacity (MCC) and end filling pressure (EFP). Data on tolerability, compliance, and adverse events (AEs) were also analyzed. RESULTS: Of the 121 patient records analyzed, 41 patients (34%) received OC at less than 5 years of age. The range of prescribed doses varied from 3 to 24 mg/d. The median treatment duration was 19 months (range, 0.3-111 months). Significant improvement of both primary efficacy outcomes was noted following OC treatment. MCC increased about 8% even after adjustment for age-related increases in MCC. Likewise, mean EFP was reduced from 33 to 21 cm H2O. More than 80% of patients showed compliance above 70%, and approximately 50% of patients used OC for more than 1 year. No serious AEs were reported; constipation and facial flushing consisted of the major AEs. CONCLUSIONS: OC is safe and efficacious in treating pediatric neurogenic bladder associated with SD. The drug is also tolerable and the safety profile suggests that adjustment of dosage for age may not be strictly observed.

Comparação da metodologia para determinação da potência de amoxicilina: método de difusão em ágar e método de espalhamento / Comparison of methods for determining the power of amoxicillin: agar diffusion assay and method of spreading

Para o sucesso do tratamento de doenças infecciosas é preciso que a concentração de agentes microbianos no local da infecção esteja adequada, para isso é necessário que a potência dos antimicrobianos nas preparações farmacêuticas que serão administradas seja precisa. Esse estudo foi feito com o objetivo de desenvolver um método de doseamento da potência de antimicrobianos alternativo ao método de difusão em ágar, apresentando como inovação a forma de aplicação dos micro-organismos testes, que é feita com o auxílio de uma alça de Drigalski. Para a realização dos testes foram escolhidos o ágar Mueller – Hinton, o Micrococcus luteus como micro-organismo teste e a amoxicilina tri-hidratada como substância teste. Foram utilizadas 18 placas de Petri e após a medição dos halos de inibição, os resultados foram comparados com os do método oficial de difusão em ágar. A partir destes resultados pode-se afirmar então que o método de espalhamento com o uso da alça de Drigalski mostrou-se válido e constitui uma metodologia alternativa, econômica, confiável e de fácil execução para a determinação da potência de antimicrobianos.

For a successful treatment of infectious diseases, antimicrobial agents used at the infection site must be at a suitable concentration. This means that the potency of the antimicrobial, in the pharmaceutical preparations being administered, must be accurately known. The purpose of this study was to develop and test an alternative to the official agar diffusion method for the determination of the potency of an antimicrobial, the innovation being the way that the test microorganisms are applied, which is done with the help of a glass loop spreader. For the tests, Mueller – Hinton agar was chosen as the medium, Micrococcus luteus as the test organism and amoxicillin trihydrate as the test antibiotic. A total of 18 Petri dishes were used and, after measurement of the inhibition zones, the results were compared with the official method of agar diffusion with a seeded top agar layer. From these results it can be said that the method of spreading the inoculum with a sterile glass loop proved valid and constitutes an economic, reliable and easier alternative method for the determination of antimicrobial potency.

Avaliação in vitro de diferentes propriedades físico-químicas de medicamentos de uso infantil / In vitro evaluation of different physicochemical properties of pediatric medicines

Objetivo: Avaliar in vitro o pH endógeno, a Acidez Total Titulável (ATT) e o oBrix de medicamentos infantis. Metodologia: A amostra foi constituída por 22 diferentes medicamentos de 5 distintas classes: antibióticos, anti-histamínicos, antiparasitários, antiinflamatórios não esteróides e corticóides. As medidas do pH foram determinadas utilizando-se o potenciômetro, a acidez total foi realizada utilizando o método da A.O.A.C e o oBrix foi determinado por refratometria. Os dados foram expressos em médias e analisou-se a diferença entre os grupos, através da ANOVA. A significância utilizada foi de 0,05 com 95% de grau de confiança.Resultados: Verificou-se que 59,1% dos medicamentos apresentaram um pH menor que 5,5, sendo portanto potencialmente erosivo aos tecidos dentais. A menor e maior média do pH foram encontradas para o Benflogin (1,75) e para o Predsim (7,35), respectivamente. Em relação à ATT, a menor média foi verificada para o Cataflan (0,01%), enquanto o maior valor foi registrado para o Infectrin (0,98%). A avaliação do oBrix revelou que o Alersin apresentou a menor média (6,25%), enquanto o Cataflan mostrou o maior valor (74,33%). Não se verificou diferença estatisticamente significativa entre as variáveis pH e a classe de medicamento (P=0,950) e entre o °Brix e a classe de medicamento (P=0,477). Todavia, verificou-se diferenças estatisticamente significante em relação à acidez total e a classe de medicamento (P = 0,000), de modo que as diferenças maiores ficaram entre as médias dos antibióticos com: os antiinflamatórios (P=0,002), os antiparasitários (P=0,003) e os corticóides (P=0,005)...

Objective: To evaluate in vitro the endogenous pH, the total titratable acidity (TTA) and o Brix of pediatric medicines. Method: The sample consisted of 22 pediatric medicines belonging to five classes: antibiotics, antihistamines, anthelmintics, non-steroid antiinflammatory drugs and corticoids. The pH was measured with a potentiometer, total acidity was obtained by the AOAC method and oBrix was determined by refractometry. The data were expressed as means and the differences among the groups were analyzed by ANOVA. The significance level was set at 0.05 with a 95% confidence level. Results: As much as 59.1% of the medicines presented pH lower than 5.5, being therefore potentially erosive to the dental tissues. Benflogin (1.75) and Predsim (7.35) presented the lowest and the highest pH means, respectively. As for TTA, the lowest mean was obtained for Cataflan (0.01%) and the highest for Infectrin (0.98%). Evaluation of oBrix revealed that Alersin presented the lowest mean (6.25%) and Cataflan (74.33%) presented the highest mean. There was no statistically significant difference among the medicine classes regarding the pH (p=0.950) or regarding the o Brix (p=0.477). On the other hand, there were statistically significant differences among the medicine classes for TTA (p=0.000); the greatest differences were found between the antibiotics and the anti-inflammatory drugs (p=0.002), the anthelmintics (p=0.003) and the corticoids (p=0.005). Conclusion: The pediatric medicines may be considered as potentially erosive to the dental tissues. In view of the statistically significant differences among the medicine classes regarding the TTA, it is recommended that the control and follow up be directed to the erosive potential of each class. The antibiotics are the class of medicine with the highest pH and acidity, and so its intake should be followed by an adequate oral hygiene...

In vitro assessment of drug resistance in Plasmodium falciparum in five States of India.

Background & objectives: In vitro assays are an important tool to assess baseline sensitivity and monitor the drug response of Plasmodium falciparum over time and place and, therefore, can provide background information for the development and evaluation of drug policies. This study was aimed at determining the in vitro sensitivity of P. falciparum isolates to antimalarials. Methods: The in vitro activity of 108 P. falciparum isolates obtained from five States of India was evaluated using WHO microtest (Mark III) to chloroquine, monodesethylamodiaquine, dihydroartesunate and mefloquine. Samples were collected from the States of Orissa, Jharkhand, Karnataka, Goa and Chhattisgarh from September 2007 to August 2009. In addition, representative samples from different States of India cryopreserved and culture adapted in the Malaria Parasite Bank of National Institute of Malaria Research, New Delhi, were also evaluated. Results: The proportion of isolates resistant to chloroquine and monodesethylamodiaquine was 44.4 and 25 per cent, respectively. Of the 27 isolates resistant to monodesethylamodiaquine, 16 (59.3%) were cross-resistant to chloroquine. No isolate showed resistance to dihydroartesunate and mefloquine. Isolates from Orissa showed the highest degree of resistance to chloroquine and amodiaquine followed by Jharkhand. Forty two isolates were genotyped for pfcrt T76K chloroquine resistant mutation; mutations were seen in 38 (90.47%) isolates. Interpretation & conclusions: The Indian P. falciparum isolates showed a high degree of resistance to chloroquine followed by monodesethylamodiaquine. No resistance was recorded to mefloquine and dihydroartesunate.

Method development and validation for naratriptan determination in human plasma by HPLC with tandem mass spectrometry detection, and its application to bioequivalence study / Desenvolvimento de método e validação para determinação de naratriptan em plasma humano por HPLC com detecção de espectrometria de massa em tandem, e sua aplicação ao estudo de bioequivalência

The authors developed a simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of naratriptan (NP) in human plasma using naratriptan-d3 (NPD3) as an internal standard (IS). Chromatographic separation was performed on a Zorbax SB-C18, 75 x 4.6 mm, 3.5 µm column with an isocratic mobile phase composed of 0.1 percent formic acid : acetonitrile (50:50 v/v), at a flow-rate of 0.6 mL/min. NP and NPD3 were detected with proton adducts at m/z 336.5→98.0 and 339.4→101.0 in selected reaction monitoring (SRM) positive mode, respectively. The liquid-liquid extraction method was used to extract the NP and NPD3. This method was validated over a linear concentration range of 0.1-25.0 ng/mL with a correlation coefficient of (r2) > 0.9998. The Intra-day and Interday precision was found to be 1.8 to 3.6 percent, and 2.3 to 2.6 percent, and accuracy to be 101.7- 104.2 percent and 101.8 to 102.9 percent, respectively. NP was found to be stable throughout freeze-thaw (three cycles), bench top and auto sampler stability studies. This method was successfully applied for the analysis of plasma samples following oral administration of NP (2.5 mg) in 31 healthy Indian male human volunteers under fasting conditions.

Os autores desenvolveram um método simples, sensível e específico de cromatografia líquida-espectrometria de massa-tandem (LC-MS/MS) para a quantificação de naratriptan (NP) em plasma humano empregando naratriptan-d3 (NPD3) como padrão interno de referência (IS). A separação cromatográfica foi realizada em coluna Zorbax SB-C18, 75 x 4,6 mm, 3,5 μm com fase móvel isocrática composta por 0,1 por cento ácido fórmico : acetronitrila (50:50 v/v) e taxa de fluxo de 0,6 mL/min. NP e NPD3 foram detectados com adutos de prótons a m/z 336.5→98.0 e 339.4→101.0 in em modo positivo do tipo monitoramento de reação selecionada (SRM), respectivamente. Extração líquido-líquido foi empregada para extrair NP e NPD3, sendo o método validado para uma faixa linear de concentração de 0,1-25,0 ng/mL resultando em coeficiente de correlação (r2) > 0,9998. A variação intra e interdia observada para precisão foi de 1,8 a 3,6 por cento e 2,3 a 2,6 por cento, respectivamente; para exatidão a variação foi de 101,7 a 104,2 por cento e 101,8 a 102,9 por cento, respectivamente. O NP se mostrou estável frente a processos de congelamento-descongelamento (3 ciclos), e estudos de estabilidade de bancada e amostragem automática. O método desenvolvido foi aplicado com sucesso para a análise de amostras de plasma após a administração oral de 2,5 mg de NP em 31 voluntários humanos, de nacionalidade indiana, sexo masculino, sob condições aceleradas.

Development and validation of a HPLC analytical assay method for efavirenz tablets: a medicine for HIV infections / Desenvolvimento e validação de um método de ensaio de HPLC analítica para comprimidos de efavirenz: um medicamento para infecções por HIV

Efavirenz is a reverse transcriptase non analog nucleoside inhibitor used to treat HIV infections. A simple assay method by high performance liquid chromatography was developed and validated for efavirenz tablets. The physical chemical characteristics of efavirenz were investigated to developing the method. The method was validated observing the parameters described in USP 29. Analyses were performed by an ultraviolet detector at a 252 nm wavelength, on a reverse-phase column (C18, 250 mm x 3.9 mm, 10 μm), using an isocratic mobile phase containing acetonitrile/water/orthophosphoric acid (70:30:0.1). The validation parameters used were: selectivity, linearity, precision, accuracy, robustness, detection and quantification limits, and all resulting data were treated by a statistical method. The results obtained confirmed an alternative assay method for efavirenz tablets adequate for routine industrial use.

O efavirenz é um inibidor não análogo de nucleosídeo da transcriptase reversa, utilizado no tratamento da infecção por HIV. Um método simples, por cromatografia líquida de alta eficiência, foi desenvolvido e validado para quantificação do efavirenz em comprimidos. O desenvolvimento do método levou em consideração as características físico-químicas do efavirenz. O método foi validado seguindo os parâmetros da USP 29. A análise foi realizada por meio de detector ultravioleta, utilizando um comprimento de onda de 252 nm, com coluna de fase reversa (C18, 250 mm x 3.9 mm, 10 μm) e fase móvel isocrática contendo acetonitrila/água/ácido ortofosfórico (70: 30: 0.1). Os critérios usados para validação foram: seletividade, linearidade, precisão, exatidão, robustez e limites de detecção e quantificação do método. Foi utilizado método estatístico em todas as etapas do processo de validação. Os resultados obtidos mostraram que o método é uma alternativa para quantificação do efavirenz em comprimidos, tornando viável seu uso na rotina industrial e laboratórios analíticos.

Beers-Fick criteria and drugs available through the Farmácia Dose Certa program / Critérios de Beers-Fick e medicamentos disponíveis no Programa Farmácia Dose Certa

CONTEXT AND OBJECTIVE: Farmácia Dose Certa is a program available in the State of São Paulo that is a national reference for providing drugs free of charge to the population. Elderly people receiving care deserve special attention regarding drugs that are appropriate for their age group. The objective was to assess the drugs in the program considered to be inappropriate for the elderly. DESIGN AND SETTING: Descriptive study evaluating free drug distribution in the State of São Paulo, Brazil. METHODS: Following the criteria proposed by Beers and Fick (drugs or drug classes that should be avoided among elderly people, independent of the diagnosis or clinical condition, because of the high risk of side effects and because other, safer drugs are available), the drugs in the Farmácia Dose Certa program that might be inappropriate for elderly people and the levels of evidence for each drug included were assessed. RESULTS: Among the available drugs, 10 (25.6 percent) were included within the Beers-Fick criteria. The drugs selected were: amitriptyline, cimetidine, diazepam, digoxin, fluoxetine, methyldopa, nifedipine, promethazine, thioridazine and ferrous sulfate. CONCLUSION: The list of drugs available within the Farmácia Dose Certa program may be considered appropriate for the general population, but not completely for the elderly population. Adjusting this list to the pharmacological aspects of aging will reduce the risks of drug interactions, falls, mental confusion and excessive sedation that result from drugs that are considered inappropriate for consumption by elderly people.

CONTEXTO E OBJETIVO: Programa Dose Certa é programa estadual para disponibilizar medicamentos de forma gratuita à população do Estado de São Paulo que é referência nacional no assunto. O segmento de idosos na população assistida merece atenção especial quanto aos fármacos adequados a este segmento etário. O objetivo foi avaliar as drogas no programa que são impróprias para idosos. TIPO DE ESTUDO E LOCAL: Estudo descritivo avaliando a distribuição de medicamentos no estado de São Paulo. MÉTODOS: Seguindo-se os critérios propostos por Beers e Fick (medicamentos ou classes deles que deveriam ser evitados em idosos, independentemente do diagnóstico ou da condição clínica, devido ao alto risco de efeitos colaterais e pela existência de outros fármacos mais seguros), avaliaram-se quais medicamentos do programa Dose Certa são impróprios para idosos e os níveis de evidência para cada medicamento incluído. RESULTADOS: Dos medicamentos disponíveis, 10 (25,6 por cento) foram incluídos nos critérios de Beers-Fick: amitriptilina, cimetidina, diazepam, digoxina, fluoxetina, metildopa, nifedipina, prometazina, tiorodazida e sulfato ferroso. CONCLUSÃO: A lista de fármacos disponível no Programa Dose Certa pode ser considerada apropriada para a população em geral, mas não totalmente para idosos. Adequá -los a aspectos farmacológicos do envelhecimento reduzirá riscos de interaç ões medicamentosas, quedas, confusão mental e sedação excessiva decorrente de medicamentos considerados impróprios para o consumo de idosos.

Determination of the melting temperature, heat of fusion, and purity analysis of different samples of zidovudine (AZT) using DSC / Determinação da temperatura de fusão, calor de fusão e pureza análise de diferentes amostras de zidovudina (AZT) por DSC

The determination of chemical purity, melting range, and variation of enthalpy in the process of characterizing medicines is one of the principal requirements evaluated in quality control of the pharmaceutical industry. In this study, the method of purity determination using DSC was outlined, as well as the application of this technique for the evaluation of commercial samples of zidovudine (AZT) (raw material) supplied by different laboratories. To this end, samples from six different laboratories (A, B, C, D, E, and F) and the standard reference (R) from the United States Pharmacopeia (USP) were analyzed. The DSC curves were obtained in the temperature range of 25 to 200 ºC under the dynamic atmosphere of N2 (50 mL min-1), heating rate of β=2 ºC min-1, using an Al capsule containing approximately 2 mg of sample material. The results demonstrated that the standard reference presented a proportion of 99.83 percent whereas the AZT samples presented a variation ranging from 97.59 to 99.54 percent. In addition, the standard reference was found to present a temperature of onset of melting point of 122.80 ºC. Regarding the samples of active agents provided by the different laboratories, a variation ranging from 118.70 to 122.87 ºC was measured. In terms of ΔHm, the samples presented an average value of 31.12 kJ mol-1.

A determinação da pureza química, a faixa de fusão e a variação de entalpia envolvida no processo de caracterização de fármacos é um dos principais requisitos avaliados no controle de qualidade em indústrias farmacêuticas. Neste trabalho é feita uma breve abordagem sobre o método de determinação de pureza utilizando DSC, assim como a aplicação desta técnica para avaliação de amostras comerciais de zidovudina (AZT) (matéria-prima) fornecida por diferentes laboratórios. Para tal, foram analisadas amostras de seis diferentes laboratórios (A,B,C,D,E e F) e a substância química de referência (R) da United States Pharmacopeia (USP). As curvas DSC foram obtidas na faixa de temperatura entre 25 a 200 ºC, sob atmosfera dinâmica de N2 (50 mL min-1), β=2 ºC min-1, utilizando cápsula de Al contendo aproximadamente 2 mg de amostra. De acordo com os resultados, pode-se observar que a substância química de referência apresentou teor igual a 99,83 por cento e que as amostras de AZT apresentaram uma faixa de variação entre 97,59 e 99,54 por cento. Pode-se verificar, ainda, que a substância química de referência apresentou uma temperatura onset de fusão igual a 122,80 ºC. Para as amostras dos princípios ativos fornecidos pelos diferentes laboratórios, pode-se verificar uma faixa de variação entre 118,70 e 122,87 ºC. No que se refere ao ΔHm, as amostras apresentaram valor médio de 31,12 kJ.mol-1.

Formulation and evaluation of mouth dissolving tablets of the etoricoxib

The demand for mouth dissolving tablets has been growing during the last decade especially for elderly and children who have swallowing difficulties. Etoricoxib is a new non-steroidal anti-inflammatory drug [NSAID] with selective cox-2 inhibitory activity, selective inhibition of cox-2 provides anti-inflammatory and analgesic activity it is commonly used for osteo-arthritis, rheumatoid arthritis, primary dysmenorrhoea, post operative dental pain and acute gout. The main criteria for mouth dissolving tablets are to disintegrate or dissolve rapidly in oral cavity with saliva in 15sec to 60sec with need of water. The disintegrants used should fulfill the criteria by disintegrating the tablets in specified time limit.in the present investigation variety of super disintegrants like primogel, kollidone, Ac-Di-sol, L-HPMC, L-HPC, were selected and tablets were prepared by direct compression method in different concentration like 4% and 8%. The prepared tablets were evaluated for weight variation, hardness, friability, in vitro disintegration time, wetting time, in vitro dissolution study, etc. formulation f-9 shows the lowest disintegration time [44sec] and wetting time [52sec]. In vitro dissolution studies revealed that formulation F-9 containning 8% L-HPC showed 97% drug release at the end of 20 min

Assessment of in vitro methodologies to determine topical and transdermal delivery of the flavonoid quercetin / Avaliação de metodologias in vitro para determinar a liberação tópica e transdérmica da quercetina

To be effective against the oxidative damages induced by UVB irradiation in the skin, the drug needs to release from the formulation in which it was incorporated and reach the skin layers where the ROS are generated. Thus, it is very important the development of a robust and sensitive methodology to extract and quantify in different skin layers the antioxidant agent delivered from topical formulations. Therefore, in the present work suitable methods to extract and quantify quercetin in skin samples and receptor phase after in vitro penetration studies were developed. The results demonstrated that the recovery from two different layers of skin, the SC and [E+D], using two different methods of quantification (DPPHò assay and HPLC, respectively), was 93.8 percent when the quercetin spiked dose was 50 µg/mL, 100.4 percent when it was 100 µg/mL and 89.9 percent for 250 µg/mL and the average recovery of the quercetin extraction from receptor phase when dichloromethane was used as extractor solvent was 96 percent. These results demonstrate that the described methods have a potential application to in vitro skin penetration studies of quercetin, since it showed to be accurate and sensitive.

Para ser efetiva contra os danos oxidativos induzidos pela radiação UVB na pele, é necessário que o ativo seja liberado da formulação na qual foi incorporado e alcance as camadas da pele onde são geradas as EROS. Desta forma, torna-se de grande importância o desenvolvimento de métodos eficazes e sensíveis para extrair e quantificar, nas diferentes camadas de pele, o agente antioxidante liberado de formulações tópicas. No presente trabalho foram desenvolvidos métodos adequados para extrair e quantificar a quercetina em amostras de pele e na fase receptora após estudos de penetração cutânea in vitro. Os resultados demonstraram que a recuperação das camadas de pele, EC e [E+D], quando do uso de duas diferentes metodologias de quantificação (ensaio de DPPHò e CLAE, respectivamente), foi de 93,8 por cento quando aplicada uma dose de 50 µg/mL de quercetina, 100,4 por cento para 100 µg/mL e 89,9 por cento para 250 µg/mL e a recuperação média da extração da quercetina da fase receptora, quando do emprego de diclorometano como solvente extrator, foi de 96 por cento. Tais resultados demonstram que os métodos descritos têm grande potencial de aplicação em estudos de penetração in vitro já que apresentaram exatidão e sensibilidade.