Avaliação dos processos de mistura de pós em farmácias magistrais utilizando planejamento fatorial: caso clonidina / Assessment of powder mixing processes in pharmacies by factorial planning: clonidine case study

O cloridrato de clonidina é um α2-adrenérgico que reduz a pressão sanguínea e retarda a estimulação cardíaca simpaticomimética. Esse fármaco é uma substância de baixo índice terapêutico que possui alta potência, sendo utilizado em baixas concentrações. Pode ser preparado em farmácias magistrais, seguindo-se rigorosos critérios de Boas Práticas de Manipulação estipulados pela Anvisa. Esse controle surgiu em razão de diversos acidentes possivelmente associados ao uso de cloridrato de clonidina manipulado. Diante disso, o objetivo deste trabalho foi avaliar o processo de mistura de pós na manipulação magistral da clonidina, buscando segurança e reprodutibilidade no referido processo. Para tanto, foram produzidas 60 cápsulas de cada lote, seguindo o planejamento fatorial 2³, em que foram estabelecidas as seguintes variáveis de entrada: processo de mistura (diluição geométrica e misturador Mixer Plus®), tamanho do invólucro gelatinoso (n°03 e 02) e concentração do fármaco (0,1 e 0,2 mg). A variável resposta para o planejamento foi o teor do fármaco nas cápsulas. Além disso, foram verificados outros parâmetros de qualidade, como o peso médio e uniformidade de conteúdo. As cápsulas obtidas encontraram-se dentro dos limites especificados pelos compêndios oficiais. Por isso, os resultados sinalizam que apesar do processo de obtenção das cápsulas ser crítico é possível obter produtos com qualidade e segurança comprovada...

Clonidine hydrochloride is an α2-adrenergic agonist that reduces the blood pressure and delays cardiac sympathomimetic stimulation. This drug has a low therapeutic index, high potency and is commonly used at low concentrations. It can be prepared at compounding pharmacies, as long as the rigorous criteria of Good Handling Practices stipulated by Anvisa are followed. This control had its origins in several accidents possibly associated with the use of compounded clonidine hydrochloride. In this context, the present study was designed to assess the powder-mixing process during the compounding of clonidine, so as to optimize its safety and repeatability. To this end, 60 capsules were produced in each batch, following 23 factorial planning, using the following input variables: mixing process (geometric dilution or Mixer Plus®), size of gelatin shell(number 03 or 02) and drug concentration (0.1 and 0.2mg). The response variable for the planning was the amount of drug inside the capsules. In addition, other quality parameters were determined, such as the average weight and content uniformity. The capsules produced were within the limits specified by official compendia. Therefore, the results indicate that, although the process of compounding capsules is critical, it is possible to have products with assured quality and safety...

Abordagem sobre os diferentes processos de secagem empregados na obtenção de extratos secos de plantas medicinais / Approach on different drying processes employed for obtaining dry extracts from medicinal plants

Na indústria farmacêutica de fitoterápicos, o extrato seco é considerado tecnologicamente viável para fins de produção em larga escala, devido à estabilidade física, química e microbiológica, além da facilidade de padronização dos princípios ativos. Entre as técnicas de secagem empregadas na preparação de extratos secos, encontra-se a nebulização ou spray-dryer, o leito de jorro, a liofilização e a evaporação rotativa. A escolha do processo de secagem é motivada pela potencialidade dos diferentes equipamentos secadores, na secagem de materiais presentes na forma líquida, no caso, soluções extrativas de plantas medicinais, fornecendo um produto de alta qualidade e com investimento relativamente baixo.

In the pharmaceutical industry of herbal medicines, the dried extract is considered technologically feasible for large-scale production, due to its physical stability, possibility of chemical and microbiological analyses and the ease of standardization of the active ingredients. Among the drying techniques used in the preparation of dry extracts are a mist or spray-dryer, the spouted bed, freeze-drying and rotary evaporation. The choice of the drying process is motivated by the potential of different drying equipments and materials present in liquid form, in this case, solutions of herbal extracts provide a high quality product and a relatively modest investment.

[Prevalence of hepatic involvement, alcoholism, hepatis B, C and HIV in patients with background history of drug use]. / Prevalencia de afectación hepática, alcoholismo, hepatitis B, C y HIV en pacientes con antecedente de consumo de drogas.

UNLABELLED: Drug addicts frequently have liver diseases for different reasons: alcohol abuse, the drugs themselves, but more often hepatitis B and C infections. AIDS is common in this population as well and could also affect the liver directly or in the form of hepatocellular or biliary damage. We conducted this study to determine the prevalence of liver diseases, alcoholism, hepatitis B and C infections, and HIV positivity in this population. We studied a cohort of 137 persons, all with a history of drug abuse, and investigated the quantity of alcohol intake, the kind of drug used, and he routes of drug administration. RESULTS: We found liver disease in 33.6%. The prevalence of alcoholism was 65.4%, of HCV 67.3%, and of HBV 17.3%. HDV was undetectable, whereas we found HIV at a frequency of 17.3%. HCV RNA was detected in 85.4% of HCV. The drug most often used was cocaine at 90.4%, followed by marihuana at 88.3%; LSD use occurred in 17.5%. We found parenteral drug use in 43.1%. We performed 22 liver biopsies, 21 associated with HCV, and detected histological changes consistent with chronic hepatitis in 17, with cirrhosis in 4, and with hepatocellularcarcinoma in 1.

Prevalencia de afección hepática, alcoholismo, hepatitis B, C y HIV en pacientes con antecedentes de consum / Prevalence of hepatic involvement, alcoholism, hepatis B, C and HIV in patients with background history of drug use

Drug addicts frequently have liver diseases for different reasons: alcohol abuse, the drugs themselves, but more often hepatitis B and C infections. AIDS is common in this population as well and could also affect the liver directly or in the form of hepatocellular or biliary damage. We conducted this study to determine the prevalence of liver diseases, alcoholism, hepatitis B and C infections, and HIV positivity in this population. We studied a cohort of 137 persons, all with a history of drug abuse, and investigated the quantity of alcohol intake, the kind of drug used, and he routes of drug administration. RESULTS: We found liver disease in 33.6%. The prevalence of alcoholism was 65.4%, of HCV 67.3%, and of HBV 17.3%. HDV was undetectable, whereas we found HIV at a frequency of 17.3%. HCV RNA was detected in 85.4% of HCV. The drug most often used was cocaine at 90.4%, followed by marihuana at 88.3%; LSD use occurred in 17.5%. We found parenteral drug use in 43.1%. We performed 22 liver biopsies, 21 associated with HCV, and detected histological changes consistent with chronic hepatitis in 17, with cirrhosis in 4, and with hepatocellularcarcinoma in 1.

Prevalencia de afectación hepática, alcoholismo, hepatitis B, C y HIV en pacientes con antecedente de consumo de drogas. / [Prevalence of hepatic involvement, alcoholism, hepatis B, C and HIV in patients with background history of drug use]

Drug addicts frequently have liver diseases for different reasons: alcohol abuse, the drugs themselves, but more often hepatitis B and C infections. AIDS is common in this population as well and could also affect the liver directly or in the form of hepatocellular or biliary damage. We conducted this study to determine the prevalence of liver diseases, alcoholism, hepatitis B and C infections, and HIV positivity in this population. We studied a cohort of 137 persons, all with a history of drug abuse, and investigated the quantity of alcohol intake, the kind of drug used, and he routes of drug administration. RESULTS: We found liver disease in 33.6

. The prevalence of alcoholism was 65.4

, of HCV 67.3

, and of HBV 17.3

. HDV was undetectable, whereas we found HIV at a frequency of 17.3

. HCV RNA was detected in 85.4

of HCV. The drug most often used was cocaine at 90.4

, followed by marihuana at 88.3

; LSD use occurred in 17.5

. We found parenteral drug use in 43.1

. We performed 22 liver biopsies, 21 associated with HCV, and detected histological changes consistent with chronic hepatitis in 17, with cirrhosis in 4, and with hepatocellularcarcinoma in 1.

Prevalencia de afección hepática, alcoholismo, hepatitis B, C y HIV en pacientes con antecedentes de consum / Prevalence of hepatic involvement, alcoholism, hepatis B, C and HIV in patients with background history of drug use

Drug addicts frequently have liver diseases for different reasons: alcohol abuse, the drugs themselves, but more often hepatitis B and C infections. AIDS is common in this population as well and could also affect the liver directly or in the form of hepatocellular or biliary damage. We conducted this study to determine the prevalence of liver diseases, alcoholism, hepatitis B and C infections, and HIV positivity in this population. We studied a cohort of 137 persons, all with a history of drug abuse, and investigated the quantity of alcohol intake, the kind of drug used, and he routes of drug administration. RESULTS: We found liver disease in 33.6%. The prevalence of alcoholism was 65.4%, of HCV 67.3%, and of HBV 17.3%. HDV was undetectable, whereas we found HIV at a frequency of 17.3%. HCV RNA was detected in 85.4% of HCV. The drug most often used was cocaine at 90.4%, followed by marihuana at 88.3%; LSD use occurred in 17.5%. We found parenteral drug use in 43.1%. We performed 22 liver biopsies, 21 associated with HCV, and detected histological changes consistent with chronic hepatitis in 17, with cirrhosis in 4, and with hepatocellularcarcinoma in 1.(AU)

In vitro dissolution test of tamoxifen citrate preparations.

The Tamoxifen Citrate is available in oral tablet and is highly used as an endocrines therapy for breast cancer. Products from assorted makers bioavailability problems has been associated to the incomplete dissolution of the tablets. We determined the dissolution in vitro of five pharmaceutical preparations of the Tamoxifen Citrate available in the Brazilian market, Novaldex, Tecnotax, Zita, Tamoxifen (TEVA) and Tamoxifeno (PHARMACIA) all containing 10 mg of active drug. The methodology was conducted according to the in vitro dissolution test from USP XXIII. Other test such as mass uniformity, content uniformity and hardness were accomplished seeking to relate physical characteristics with the in vitro dissolution of these preparations. All the formulations presented liberation more than 75% of the active drug in 30 minutes. Any relationship was not observed between the in vitro dissolution, the average weight, the mass uniformity and the hardness of the tablets whereas the liberation was proportional to the tamoxifen citrate content. Although one of the tested products did present a higher dissolution profiles in comparison to the other tested preparation.

Ilheus virus (Flaviviridae, Flavivirus) is closely related to Japanese encephalitis virus complex.

The Ilheus (ILH) virus has long been known to belong to group B of the arboviruses. Previous attempts to relate it to existing serogroups within the Flavivirus genus using conventional serological techniques such as hemagglutination inhibition, neutralization and complement fixation tests have been inconclusive. We have first used denaturing gel electrophoresis to estimate the molecular weight of immunoprecipitated radiolabeled viral proteins and the cross-reactivity among ILH proteins and hyperimmune sera to several flaviviruses only from the mosquito-borne encephalitis virus serogroups. The estimated molecular weight for the three proteins was in the same order of magnitude, as previously established, for mosquito-borne flaviviruses. Cross-immunoprecipitation tests showed that NS3 protein is the most cross-reactive. Partial nucleotide sequence analyses of the NS3 gene, corresponding to an area linking the helicase and the RNA triphosphatase domains, revealed that ILH virus is very closely related to the Japanese encephalitis virus complex confirming earlier serological data.

[Hepatic lesions in acute cardiovascular failure in necropsy specimens]. / Valoración del daño hepático en el fallo agudo cardiocirculatorio en material de necropsias.

To evaluate quali-quantitatively ischemic liver injury due to acute cardiocirculatory failure (ischemic hepatitis), and its real clinical signification, 200 out of 1165 autopsy records with ACF clinical diagnosis were selected; 33/200 (16.5%) shown centrilobular necrosis without inflammatory component, accompanied or not by midzonal compromise. Grade IV centrilobular necrosis (50-100% involved lobules) was present in 96.9%, with 15.5% associated midzonal pattern, and 21.2% of confluent type; 2 additional cases with isolated midzonal necrosis (5.7%) were seen. Only six patients (3.0% of ACF patients, and 18.2% of those with histological injury) shown overt clinical liver disease, one of them with a fulminant hepatitis picture (0.5% of ACF, and 3.0% of patients with ischemic necrosis). Bilirubin levels were 3.4-10.2 mg%, and aminotransferases rose up to 540 times over their seric superior normal limits. Centrilobular necrosis involved 100% of lobules in all cases.

Valoración del daño hepático en el fallo agudo cardiocirculatorio en material de necropsias. / [Hepatic lesions in acute cardiovascular failure in necropsy specimens]

To evaluate quali-quantitatively ischemic liver injury due to acute cardiocirculatory failure (ischemic hepatitis), and its real clinical signification, 200 out of 1165 autopsy records with ACF clinical diagnosis were selected; 33/200 (16.5

) shown centrilobular necrosis without inflammatory component, accompanied or not by midzonal compromise. Grade IV centrilobular necrosis (50-100

involved lobules) was present in 96.9

, with 15.5

associated midzonal pattern, and 21.2

of confluent type; 2 additional cases with isolated midzonal necrosis (5.7

) were seen. Only six patients (3.0

of ACF patients, and 18.2

of those with histological injury) shown overt clinical liver disease, one of them with a fulminant hepatitis picture (0.5

of ACF, and 3.0

of patients with ischemic necrosis). Bilirubin levels were 3.4-10.2 mg

, and aminotransferases rose up to 540 times over their seric superior normal limits. Centrilobular necrosis involved 100

of lobules in all cases.

Novas tentativas para melhoramento da producao do antibiotico antraciclinico miniatomicina. / New attemps for the improvement of the production of anthracyclinic miniatomycin antibiotic

Neste trabalho apresentam-se os resultados de estudos objetivando melhorar a potencialidade do Streptomyces coeruleorubidus v. miniatomyceticus IA-4362, como produtor do complexo antibiotico miniatomicina, utilizando-se mutantes ou variantes da referida cepa, obtidas pelos metodos de mutacao natural baseado na "Population Pattern" e meios adicionados de diferentes concentracoes do proprio complexo antibiotico miniatomicina.Diferentes meios e condicoes de cultivo foram analisados

[O and C prenylated chalcones with antineoplastic and antibiotic activities isolated from Lonchocarpus neuroscapha Benth]. / Chalconas o- ec-preniladas com atividades antibiótica e antineoplásica, isoladas de Lonchocarpus neuroscapha Benth

In the course of our program on the antimicrobial and antineoplastic substances from higher plants we have studied many flavonoid compounds isolated from root back of Lonchocarpus neuroscapha Benth. In the present paper a slight effect on sarcoma 180 and Ehrlich carcinoma of cordoin, 4-hydroxy-cordoin and 4-hydroxy-derricin, as well as the only observed effect of derricin on sarcoma 180 were observed. The antimicrobial action of four prenylated chalcones, i.e. 4-hydroxy-derricin, 4-hydroxy-lonchocarpin, 4-hydroxy-cordoin and 4-hydroxy-isocordoin is reported.

[Antimicrobial substances of superior plants. 44. Isolation of diterpene acid from Croton aff. argyrophylloides Muell arg. (Euphorbiaceae)]. / Substáncias antimicrobianas de plantas superiores. comunicação XLIV. Isolamento de um ácido diterpènico de Croton aff. argyrophylloides Muell arg. (Euphorbiaceae)

In this paper the authors present the first report concerning the biological effects of a diterpene isolated from Croton aff. argyrophylloides Muell. Arg (Euphorbiaceae). Some biological and physiochemical properties of the antibiotic, named argyrophillic acid, were appreciated in comparison with those presented by cunabic acid, an antibiotic isolated from Icthyothere cunabi. The authors still show the microbial action of the abietic acid and confront it with that of the argyrophilic acid, the new antibiotic here reported.