Midazolam and haloperidol for palliative sedation: physicochemical stability and compatibility of parenteral admixtures

This study was done to determine the time while the binary admixtures with midazolam and haloperidol drugs are administered by perfusion to the patients in the clinical routine. Samples with different concentrations of both drugs were prepared following the usual clinical practice. Solvents used were 0.9 % sodium chloride solution and 5% dextrose, and viaflo plastic bags were used as the containers of the admixtures. Samples were not protected from light and were stored at 20 ºC or at 4 ºC. Compatibility and physicochemical stability were studied by visual inspection, turbidity measurement, pH determination and ultraviolet detection high performance liquid chromatography (UV-HPLC) was used to determine midazolam and haloperidol concentrations. The assay was validated following the FDA and EMA guidelines. Darunavir was used as internal standard (IS). For the studied admixtures, turbidity measurements and pH determinations showed little changes in function of the time. Haloperidol and midazolam concentrations determined by HPLC are within the acceptable range of drug concentrations, which are considered stable for four days in case of admixtures stored at 20 ºC and for seven days for refrigerated admixtures. Taking into account the microbiological risk matrix, the compatibility and the chemical and microbiological stability of the midazolam and haloperidol in the co-administered admixtures in viaflo plastic bags with 0.9 % sodium chloride solution and 5% dextrose can be set as 48 hours when samples are stored at 20 ºC and one week if they are refrigerated.

Organic cocoa extract -loaded surfactant-based systems intended to skin bioadhesion

ABSTRACT This study was to develop, characterize, and evaluate the physical-chemical stability, in vitro antioxidant activity and in vitro safety profile of liquid crystalline systems (LCS) and microemulsions (MEs) with and without organic cocoa (OC) extract. LCS stabilized by surfactant polyoxyethylene 20 cetyl ether, containing water and oleic acid were studied. LCS and MEs were characterized using polarized light microscopy, small angle X-ray scattering, rheology and in vitro bioadhesion, and were evaluated for a period of 30 days by visual aspects, centrifuge test, pH value and relative density. PLM and SAXS assays showed the presence of domains of MEs, cubic and hexagonal mesophasephases, varying the proportions of the components of the formulations; where in the addition of the extract did not change rheological behavior of the formulations. All of the formulations were stable in the period analyzed and presented higher bioadhesive strength. In vitro antioxidant activity suggests that LCS and MEs presented a high capacity to maintain the antioxidant activity of OC extract. The results showed that the incorporation of OC in LCS improved the safety profile, according to cytotoxicity assays of systems may be a promising platform to OC extract for topical application for the potential treatment of skin disorders.

Guava: phytochemical composition of a potential source of antioxidants for cosmetic and/or dermatological applications

ABSTRACT Guava (Psidium guajava L.) is a native fruit of the American tropics with commercial applications for its taste, flavor and aroma. Numerous pharmacological uses have been described for it, such as the antiseptic effect of its leaves, the use of the fresh fruit and tea from its leaves for the treatment of diarrhea, dysentery, diabetes mellitus, and others. However, considering its rich composition, the guava also is a potential source of antioxidants to be used in the development of new formulations for cosmetic and/or dermatological applications, the main focus of this research. Herein, we describe the study of the phytochemical composition and the antioxidant activity of a guava extract prepared with non-toxic solvents aiming its use at biological applications. High performance liquid chromatography and mass spectrometry were employed to identify the major components, while thermoanalytical measurements and hot stage microscopy were used to assess the chemical stability of guava fruit extract. The antioxidant activity was also evaluated assessing the SOD-like activity and ABTS free radical scavenger. The results show that the extract is a rich source of phenolic compounds, such as quercetin, kaempferol, schottenol, among many others. All of the components found in guava extract exhibit biological effects according to the literature data, mainly antioxidant properties.

Factors to consider in developing individual pharmaceutical product quality risk profiles useful to government procurement agencies

Governments that procure pharmaceutical products from an Essential Medicine List (EML) bear special responsibility for the quality of these products. In this article we examine the possibility of developing a pharmaceutical product quality risk assessment scheme for use by government procurement officials. We use the Chinese EML as a basis, and US recall data is examined as it is publically available.This is justified as the article is only concerned with inherent product quality risks. After establishing a link between Chinese essential medicines and those available in the US, we examine US recall data to separate product specific recalls. We conclude that, in addition to existing manufacturing based risks, there are two other product specific risks that stand out from all others, degradation and dissolution failure. Methodology for relative product risk for degradation is needed to be developed and further work is required to better understand dissolution failures which largely occur with modified-release solid oral products. We conclude that a product specific quality risk profile would be enhanced by including a risk assessment for degradation for all products, and in the case of solid oral products, dissolution.

Analysis of the chemical stability of Morinda officinalis oligosaccharides during extraction / 中国药学杂志

OBJECTIVE: To study the chemical stability of oligosaccharides in Morinda officinalis (M. officinalis) extracted with different solvents. METHODS: The change of M. officinalis oligosaccharides extracted with water, ethanol, and aqueous solutions at different pHs was detected by HPTLC. RESULTS: The oligosaccharides began to constantly hydrolyze after 0.5 h when being extracted with water for different time. There was a fall of oligosaccharides concentration while the contents of fructose and sucrose were on the rise. New unknown compositions were generated after 0.5 h. When M. officinalis oligosaccharides were extracted with different percentages of ethanol, it only hydrolyzed when ethanol was in the range of 10%-30%, with little unknown compositions. Oligose was almost completely hydrolyzed at pH 2-3 but the hydrolyzation was alleviated at pH 3-4, with many kinds of new unknown composition generated. The oligosaccharides became stable when the pH was between 6 and 10. CONCLUSION: M. officinalis oligosaccharides is unstable in water, but rather stable in ethanol. However, there is significant difference in aqueous solutions at different pHs.

Development and stability assessment of liquid paediatric formulations containing sildenafil citrate

The purpose of this study is to develop and improve oral liquids formulations of sildenafil citrate for paediatric use. Four different formulations were developed, which are as follows: two aqueous solutions of sildenafil citrate (2.5 mg/mL), with or without preservatives, and two other solutions of sildenafil in simple syrup (1.25 mg/mL), with or without preservatives. All of the formulations were physically, chemically and microbiologically stable for three months. The results of the stability studies allowed for the optimisation of formulations without preservatives due to their simplicity and their similar stable conditions when compared to the formulations containing antimicrobials. The shelf life of both formulations was three months; however, upon opening, aqueous solutions should be used within 10 days and kept refrigerated, and syrup solutions should be used within 14 days in a hospital setting.

O objetivo deste trabalho é desenvolver e otimizar formulações líquidas orais de citrato de sildenafil adequadas ao uso pediátrico. Foram desenvolvidas quatro formulações diferentes: duas soluções aquosas de citrato de sildenafila (2,5 mg/mL) com ou sem conservantes e duas soluções de citrato de sildenafil em xarope simples (1,25 mg/mL) com ou sem conservantes. Todas as formulações desenvolvidas apresentaram estabilidade quer físico-química quer microbiológica durante 3 meses. Os resultados dos estudos de estabilidade permitiram otimizar as formulações isentas de conservantes, uma vez que estas eram mais simples e apresentavam do mesmo modo uma boa estabilidade, comparando com as formulações que continham conservantes. O período de utilização de ambas as formulações é de três meses, no entanto, após abertura do frasco, a solução aquosa deve ser utilizada durante 10 dias, acondicionada no refrigerador e o xarope deve ser utilizado durante 14 dias, mesmo em ambiente hospitalar.

Análise das soluções de hipoclorito de sódioutilizadas por endodontistas / Evaluation of sodium hypochlorite solutionsused by endodontists

Introdução: O sucesso da terapia endodôntica está condicionado adiversos fatores, entre os quais o uso de substâncias químicas deboa qualidade. Objetivo: Neste trabalho investigaram-se algumascaracterísticas das soluções de hipoclorito de sódio utilizadas emclínicas de atendimento, tais como concentração, pH e armazenagem.Material e métodos: Para isso, distribuiu-se formulário com perguntasrelativas à solução empregada a 100 endodontistas, além de pedir-lhes100 ml do produto. As amostras foram levadas ao laboratório paraanálise por titulometria da concentração de cloro residual livre, bemcomo do pH das soluções, com o auxílio de um peagômetro. Resultados:Apenas 1% dos profissionais conhece o valor do pH das soluções. Dasamostras recolhidas, 36% apresentaram pH 9, 22% pH 10, 16% compH 13, 14% pH 12, 11% pH 11 e 1% pH 8. Quanto aos profissionais,37% mantinham seus frascos sob refrigeração e 67% em temperatura ambiente. Conclusão: Os endodontistas usam soluções de hipocloritode sódio diferentes daquelas que desejam por desconhecerem ascondições necessárias para a manutenção da estabilidade química.

Introduction: The success of endodontic therapy is conditioned byseveral variables, being the use of good quality chemical agents one ofthem. Objective: In this study, some characteristics of commonly usedsodium hypochlorite irrigants were investigated, such as: concentration,pH, and storage conditions. Material and methods: For this purpose, aquestionnaire comprising questions regarding the employed irrigant wassent to 100 endodontists. Besides that, a 100mL sample of the sodiumhypochlorite irrigant used by them was collected. Free residual chlorinedetermination was laboratorially carried out through titration method.Additionally, pH was measured, through peagameter reading. Results:Only 1% of the professionals did know the pH value of the solutionsused by them. Concerning to pH value, 36% of the solutions presentedpH 9; 22%, pH 10; 16%, pH 13; 14%, pH 12; 11%, pH 11; and 1%, pH8. 37% of the endodontists kept the solution flasks under refrigeration,and 67% kept them at environmental temperature. Conclusion: It can beconcluded that the endodontists are using altered hypochlorite solutionsbecause they fail to observe the necessary conditions for maintainingthe solution?s chemical stability.

Shelf-life of a 2.5 percent sodium hypochlorite solution as determined by arrhenius equation

Accelerated stability tests are indicated to assess, within a short time, the degree of chemical degradation that may affect an active substance, either alone or in a formula, under normal storage conditions. This method is based on increased stress conditions to accelerate the rate of chemical degradation. Based on the equation of the straight line obtained as a function of the reaction order (at 50 and 70 ºC) and using Arrhenius equation, the speed of the reaction was calculated for the temperature of 20 ºC (normal storage conditions). This model of accelerated stability test makes it possible to predict the chemical stability of any active substance at any given moment, as long as the method to quantify the chemical substance is available. As an example of the applicability of Arrhenius equation in accelerated stability tests, a 2.5 percent sodium hypochlorite solution was analyzed due to its chemical instability. Iodometric titration was used to quantify free residual chlorine in the solutions. Based on data obtained keeping this solution at 50 and 70 ºC, using Arrhenius equation and considering 2.0 percent of free residual chlorine as the minimum acceptable threshold, the shelf-life was equal to 166 days at 20 ºC. This model, however, makes it possible to calculate shelf-life at any other given temperature.

Testes acelerados de estabilidade são indicados para avaliar, em um curto período de tempo, o grau de degradação química que poderá afetar uma substância química, isoladamente ou quando inserida em uma fórmula, sob condições normais de armazenamento. Este método está fundamentado na intensificação das condições de estresse para acelerar a velocidade de degradação química. Baseando-se na equação da reta obtida e na ordem de reação determinada (a 50 e 70 ºC) e usando a equação de Arrhenius, a velocidade de reação foi calculada para a condição de temperatura de 20ºC (condições normais de armazenamento). Este modelo de teste acelerado de estabilidade torna possível a predição da estabilidade química de qualquer substância, em qualquer tempo, desde que o método de quantificação da substância química esteja disponível. Como exemplo da aplicabilidade da equação de Arrhenius em teste acelerado de estabilidade, uma solução de hipoclorito de sódio a 2,5 por cento foi analisada por ser quimicamente instável. A quantificação do cloro residual livre foi determinada através de titulação iodométrica. A partir dos dados obtidos decorrentes das amostras submetidas às temperaturas de 50 e 70 ºC e com o emprego da equação de Arrhenius, o tempo de prateleira obtido foi de 166 dias em temperatura de 20 ºC, considerando como limite inferior a concentração de 20 mg/mL de cloro residual livre. Este modelo, entretanto, possibilita o cálculo de tempo de prateleira em qualquer outra temperatura de interesse.

Study on Stability of Aqueous Solution of Ferulic Acid / 中成药

The chemical stability of aqueous solution of ferulic acid was studied by the constant temperature accelerated test according to the princiPle of chemical dynamics. The ferulic acid in sample was determined by HPLC. The result showed that the decomposition of ferulic acid in aqueous solution accords with the primary reaction. At room temperature (25℃),the time of decomposition of 10℃ ferulic acid in aqueous solution (the expiry date of drug) was calculated robe 19. 36mo and 17.41 too-20. 69mo,calculated by classical and simple calculation methods, respectively.

Chemical Stability of Disposable Infusion Bag of Total Parenteral Nutrition / 中国药房

OBJECTIVE:To study the chemical stability of disposable infusion bag of total parenteral nutrition.METHODS:0.9% sodium chloride injection was infused into the disposable infusion bag of total parenteral nutrition and set at 8 ℃ or 37 ℃ for different duration(0,24,48,and 72 h) as sample solution.The sample solution was compared with blank control(0.9% sodium chloride injection contained in glass bottle) in respect of pH value,metal ion,indissoluble particle,chloride,reduction substance,UV absorbance and dissolution of cyclohexanone.RESULTS:Each index was stable when sample solution was set at 8 ℃ for 24 h.Reduction substance and dissolution of cyclohexanone increased when solution was set at 37 ℃ with time prolonged,as compared with blank control.At 37℃ UV absorbance is more than that at 8 ℃.CONCLUSION:It is suitable to set disposable infusion bag of total parenteral nutrition at 8 ℃ after infusing with injection and use up within 24 h.