Consumption of medicines in high-risk pregnancy: evaluation of determinants related to the use of prescription drugs and self-medication

The use of drugs during pregnancy still represents a challenge for medicine, since the majority of drugs cross the placental barrier with a potential to cause several congenital problems to the fetus, and most of them have not been clinically tested in pregnant patients. At the same time, the medicalization phenomenon, self-medication, and lack of patient information about the misuse of medicines are additional problems. Thus, the aim of this study was to evaluate the pattern of medicine consumption in high-risk pregnancies and the determinants related to this consumption pattern. In order to do so, a cross-sectional descriptive study was performed with puerperal women who had a history of high-risk pregnancy. Statistically significant associations were found between self-medication and fewer prenatal visits, and cigarette use during pregnancy and a higher number of children. According to these data, the vulnerability of this population to the risks of drug use is evident, demonstrating a gap that requires urgent interventions in health-care education.O uso de medicamentos na gestação representa, ainda hoje, um desafio para a medicina, visto que grande parte dos fármacos atravessa a barreira placentária e, na maioria, não foi testada clinicamente em gestantes, podendo vir a ocasionar diversos problemas congênitos ao feto. Ao mesmo tempo, a automedicação, o fenômeno da medicalização e a falta de informação sobre os riscos do mau uso de medicamentos são problemas adicionais. Diante disto, o objetivo deste estudo consistiu em avaliar o padrão de consumo de medicamentos na gestação de alto risco e os determinantes relacionados ao seu padrão de consumo. Para tanto, realizou-se um estudo descritivo de corte transversal com puérperas, que apresentaram gestação de alto risco. Verificaram-se associações estatisticamente significativas entre automedicação e mulheres com menor número de consultas de pré-natal, uso de cigarro na gestação e maior número de filhos. De posse destes dados, fica evidente a vulnerabilidade dessa população aos riscos decorrentes do uso de medicamentos, sendo esta lacuna um campo de prática com necessidade de intervenções urgentes no âmbito da educação em saúde

Determination of the critical hydrophile-lipophile balance of licuri oil from Syagrus coronata: application for topical emulsions and evaluation of its hydrating function

The aims of this study were to determine the critical hydrophile-lipophile balance (HLB) of licuri oil, and to perform a clinical assay to evaluate its hydrating effects. For the determination of the HLB, serial emulsions were prepared with the oil. Regarding the clinical study, 13 human subjects were recruited to evaluate the hydrating power of the emulsified preparation containing licuri oil, and comparing it with the same preparation containing sweet almond oil (SAO). The critical HLB of licuri oil was represented by the zones within the concentrations of 10% for the oil and 15% for the pair of tensoactive agents, with a value of 11.8. Both preparations showed similar hydrating power. We propose that licuri oil can be considered a new lipophilic adjuvant with hydrating characteristics, which can be used in cosmetic preparations, replacing consecrated oils, such as SAO.O objetivo deste estudo foi determinar o EHL crítico do óleo licuri e realizar um ensaio clínico para avaliar os seus efeitos hidratantes. Para a determinação do EHL foram preparadas emulsões seriadas contendo esse óleo. Em relação ao estudo clínico, avaliamos o poder hidratante de preparação emulsionada com óleo de licuri, comparando-a com a mesma preparação contendo óleo de amêndoas doces (OAD), em 13 voluntários. O EHL crítico do óleo de licuri foi representado pelas zonas dentro das concentrações de 10% para o óleo e 15% para o par de tensoativos, com um valor de 11,8 e ambas as preparações mostraram poder hidratante similar. Desta forma, o óleo de licuri pode ser considerado um novo adjuvante lipofílico com função hidratante, o qual pode ser usado em preparações cosméticas, substituindo óleos de consagrado uso, tais como o OAD

Desenvolvimento e validação de um método para quantificação de norfloxacino por cromatografia líquida de alta eficiência e aplicação a estudo de farmacocinética comparada em voluntários humanos

The development and validation of a simple and accurate method based on HPLC with ultraviolet detection for the quantification of norfloxacin (NFX) in human plasma and its application to a bioequivalence study between two norfloxacin formulations is described. NFX and the internal standard (cyprofloxacin) were extracted from plasma using liquid-liquid extraction. Chromatographic separation of norfloxacin, cyprofloxacin and plasma interferents was achieved with a C-18 column and a mobile phase consisting of 20 mM sodium hydrogen phosphate buffer pH 3.0 and acetonitrile (88:12, v/v) and quantitation was done at 280 nm. The method was linear from 25 to 3000 ng mL-1 (r² >; 0.997578), and norfloxacin and cyprofloxacin had an average recovery from plasma of 93.9% and 91.2% respectively. The RSD of inter-day quality control samples at the lower limit of quantification was less than 15%. After a single oral dose (400 mg) of norfloxacin administered to healthy human volunteers using a randomized 2x2 crossover design, pharmacokinetic parameters (AUC0-t, AUC0-;¥;, Cmax, t1/2) were derived from the plasma concentration curves for both formulations. Pharmacokinetic analysis of the data showed that the two formulations were bioequivalent, while no adverse reactions to the drug were observed.O desenvolvimento e validação de um método simples e preciso por CLAE-UV para quantificação de norfloxacino (NFX) em plasma humano e a sua aplicação a um estudo de bioequivalência entre duas formulações são descritos. NFX e o padrão interno (ciprofloxacino, PI) foram extraídos do plasma através de extração líquido-líquido. A separação cromatográfica do NFX, do PI e dos interferentes do plasma foi realizada com uma coluna C-18 e fase móvel composta de tampão fosfato de sódio 20 mM pH 3,0 e acetonitrila (88/12, v/v) e quantificado em 280 nm. A resposta do detector aos analitos mostrou-se linear entre 25 a 3000 ng mL-1 (r² >; 0,997578) e a recuperação média de NFX e PI foi de 93,9% e 91,2% respectivamente. O desvio padrão relativo de amostras analisadas ao nível do limite inferior de quantificação foi menor que 15%. Foi administrada uma dose de NFX (400 mg) por via oral a voluntários humanos em um estudo aberto, aleatório e cruzado 2x2 entre duas formulações. Os parâmetros farmacocinéticos (AUC0-t, AUC0-;¥;, Cmáx, T1/2) foram observados a partir da curva de concentração versus tempo. A análise farmacocinética mostrou que as duas formulações são bioequivalentes entre si. Nenhum efeito adverso foi observado

Metronidazole thermogel improves retention and decreases permeation through the skin

Metronidazole (MTZ) is widely used as the standard antibiotic for the treatment of rosacea and, more recently, is being used off label in Brazilian hospitals for the treatment of wounds. Following oral administration, minimal amounts of active agent reaches the skin and side effects are strongly induced. Consequently, MTZ is currently being applied topically in order to improve the therapeutic efficacy with reduced side effects, with Rozex(r) (RZ) (an MTZ gelled formulation) being the only marketed product. This study examined whether the use of MTZ 0.75% from thermogel formulations could improve drug retention and reduce dermal exposure compared to that by Rozex(r). Following a 21 h permeation study, the highest total amount of MTZ permeated through the rat healthy and disturbed skin was seen with Rozex(r), but similar to all formulations regardless of the skin condition. On the other hand, the amount retained in the epidermis/dermis was larger for thermogel formulations; at least 4 fold that of Rozex(r), when the stratum corneum was present as a barrier. In conclusion, thermogel formulations can be favorable alternatives to Rozex(r) for the topical application of MTZ with improved efficacy and reduced side effects

Preliminary development of lapachol gel: in vitro permeation study

O objetivo do presente estudo foi desenvolver formulações geleificadas do lapachol, substância de conhecida atividade antiinflamatória. Para otimização das formulações, foi verificada a influência da resina de Carbopol® empregada (934P, 940 e 941), do pH da formulação (5, 7 e 8), da concentração do princípio ativo (0,2%, 0,5% e 1,0%) bem como da incorporação de um promotor de absorção (Polissorbato 80) na liberação in vitro do lapachol utilizando células de difusão tipo Franz. Para tanto foram usadas como barreiras membrana sintética Durapore® e pele de rato albino tipo Wistar. Os resultados demonstraram que a adição do Polissorbato 80 na formulação promoveu aumento significativo na permeação do princípio ativo através da pele estudada, exceto para os géis contendo 0,2% de lapachol utilizando Carbopol® 934P como agente geleificante. Estes géis apresentaram as melhores taxas difusionais de lapachol, principalmente quando incorporados em formulações com pH 8, nas concentrações de 0,5% ou 1,0% de princípio ativo. Todavia as preparações contendo 1,0 % de princípio ativo apresentaram pequenos cristais de lapachol não solubilizados.The scope of this work was to develop two gel formulations containing lapachol, substance with known anti-inflammatory activity. In order to achieve a more effective topical delivery, the effects of vehicles and enhancers were evaluated. The influence of the Carbopol® resin (934P, 940 and 941), the pH of the formulation (5, 7 and 8), the concentration of the active (0.2%, 0.5% and 1.0%) and the incorporation of Tween® 80 were investigated. A series in vitro permeation studies were conduct in classical Franz-type diffusion cells using Durapore® synthetic membranes and Wistar mouse skins as barriers. Through the careful analyse of the data obtained, we could observe that the addition of Tween® 80 leads to a significant increase in the in vitro diffusion of the active, except for the formulations containing Carbopol® 934P and 0.2% of lapachol. The formulations assayed presented best in vitro diffusion rates of lapachol at pH 8 when 0.5% or 1.0% of the active was added. However, the preparations containing 1.0% of drug presented little insoluble crystals of lapachol

Reversed phase HPLC determination of tamoxifen in dog plasma and its pharmaco-kinetics after a single oral dose administration

The analytical method developed to evaluate tamoxifen in dog plasma samples was precise, accurate, robust and linear in the range of 5-200 ng/mL. The limits of detection and quantification were 0.981 ng/mL and 2.97 ng/mL, respectively. Besides, the intra-day precision and accuracy variations were 8.78 and 10.16%, respectively. Tamoxifen concentrations were analyzed by combined reversed phase liquid chromatography and UV detection (lambda=280 nm). The study was conducted using an open randomized 2-period crossover balanced design with a 1-week washout period between the doses. This simple, rapid and selective method is suitable for pharmacokinetic, bioavailability and bioequivalence studies

Topical bio(in)equivalence of metronidazole formulations in vivo

The topical bioavailabilities of metronidazole from a commercially available ‘reference’ product (Rozex®) and two extemporaneous test formulations were compared. With the reference drug product, a full skin pharmacokinetic profile, in vivo in human volunteers (following a 6-h uptake and clearance over the subsequent 22 h), was obtained using an improved stratum corneum (SC) sampling procedure. Then, a two-time point SC sampling method enabled the bio(in)equivalence of the test formulations to Rozex® to be evaluated. One test formulation was shown to be bioequivalent to Rozex®, both for uptake and clearance, whereas the other (more viscous and less spreadable) formulation was not. The delivery of metronidazole into the underlying viable epidermal tissue from Rozex® and from the equivalent test formulation was 2.5 to 3.5-fold higher than that from the inequivalent extemporaneous vehicle. The results highlight that the quantitative composition of a formulation, as well as its physical properties that influence events that take place at the vehicle-skin interface, can have a dramatic impact on the delivery of drug into the SC and subsequently to the viable skin layers below. The reproducible, sensitive and facile in vivo methodology employed may prove of particular value where regulatory approval of generic formulations lacks objective rigour.</p

Quality evaluation of a Brazilian marketed herbal medicine made from Schinus terebinthifolius Raddi: changes in the legislation for registration throughout 20 years / Avaliação da qualidade de um medicamento à base Schinus terebinthifolius Raddi (aroeira) comercializado no Brasil: adequação à legislação ao longo de 20 ano

Considering the importance of the evaluation of quality and performance attributes of herbal medicines, this work evaluated a gynecological gel containing aroeira (Schinus terebinthifolius Raddi), which was previously registered in 2001, and is still marketed in Brazil. Using the updated guides and legislation as a basis, the product was evaluated by checking the pH, spreadability, rheological behavior, in vitro release test, ex vivo permeation and retention study using porcine vaginal mucosa in Franz diffusion cells, and histological evaluation of the porcine vaginal mucosa before and after application of the product. After the permeation study, it was verified that gallic acid (chemical marker quantified) does not cross the mucosa, therefore, it is safe for local use. In addition, the pH of the formulation is within the range considered normal for use in healthy women. Finally, the histological evaluation of the mucosa showed changes compatible with the application of tannins (major compounds of the plant), and without changes indicative of loss of tissue integrity.