Development of a validated stability-indicating HPLC- DAD method for dasabuvir and the characterization of its degradation products using LC-QToF-MS/MS

Abstract A stability-indicating HPLC-DAD method was developed and validated for the simultaneous determination of dasabuvir and its degradation products in the pharmaceutical formulation. The proposed method utilized a Symmetry® C18 (4.6 x 75 mm, 3.5 µm) column, and the mobile phase consisted of an isocratic elution of formic acid (0.1%) and acetonitrile (55:45, v/v), at a flow of 1 mL min-1; analytes were detected at 244 nm. Dasabuvir was submitted to different stress degradation conditions, such as acidic, alkaline, neutral, thermal, oxidative and photolytic, and the structural elucidation of degradation products was performed using LC-QToF-MS/MS. The HPLC-DAD stability-indicating method was validated for selectivity, linearity, limit of detection and quantification, accuracy, precision and robustness, according to ICH guidelines. Dasabuvir produced two degradation products (DP1 and DP2) from the alkaline stress conditions, which were characterized in negative ion mode. Dasabuvir was linear in the range 9.78 to 136.92 µg mL-1, and DP and DP were linear in the range 2.9 to 20.2 µg mL-1 and 1.3 to 14.9 µg mL-1, respectively. The 1 2 recovery ranged between 99.16 and 100.86%, while precision ranged from 1.02 to 2.89%. As the method can effectively separate the dasabuvir from its degradation products and quantitate them, it may be employed as a stability-indicating method for the pharmaceutical formulation.

Development and in vivo evaluation of lipid-based nanocarriers containing Jatropha isabellei dry extract from the dichloromethane fraction intended for oral treatment of arthritic diseases

In this study, a dichloromethane fraction dry extract from the underground parts of Jatropha isabellei (DFJi) was used to prepare lipid nanocarriers (LNCJi) aimed at providing the oral delivery of terpenic compounds in the treatment of arthritis. The lipid nanocarriers were prepared by the spontaneous emulsification method. The lipid nanocarriers displayed sizes ranging from 180 to 200 nm and zeta potential values of around -18 mV. A high value of entrapment efficiency (> 90%) was obtained for jatrophone, which was used as the chemical marker of DFJi. LNCJi stored at 4°C were demonstrated to be stable through measurements of transmitted light after analytical centrifugation of the samples. In vitro drug release studies conducted in biorelevant dissolution media demonstrated that jatrophone release was faster from LNCJi than from free DFJi. When tested in an acute arthritis model, the LNCJi exhibited antinociceptive properties after oral administration of a 50 mg/kg dose, unlike the free DFJi, although no reduction in articular diameter was observed. These results suggest that an increase in the oral absorption of DFJi constituents may have occurred through the carrying of this fraction in LNCJi, thus improving the antinociceptive activity of this compound

Formulation And Characterization Of Solid Lipid Nanoparticles Containing Ginger Oil For Enhancement Of Stability

Objective: To develop and characterize ginger oil loaded solid lipid nanoparticles (SLN) for enhancement of its stability. Methods: Ginger oil loaded SLNs were prepared in four different batches by double emulsification method using different concentrations of soya lecithin and Tween 80. Further, these batches were characterized for particle size, zeta potential, drug entrapment efficiency and in vitro release study. After observing the results, batch F4 was further characterized by Fourier Transform Infrared Spectroscopy (FTIR), Transmission Electron Spectroscopy (TEM) and Differential Scanning Calorimetry (DSC). In addition the optimized batch was subjected to anti-microbial study. Finally, stability studies were done by storing the F4 formulation at accelerated condition, room temperature, refrigerated temperature and photostability were performed by exposing the formulation to UV/fluorescence lamp for 6 mo. Results: The encapsulation efficiency of various batches of SLNs was in the range of 79.75 to 90.24%. The size ranges varied between 50 to 1000 nm. Zeta potential of all formulations was found to be in the range of-44.52 to-49.37 mV. The FTIR spectra of optimized F4 batch indicated no significant structural changes or complexation reactions between drug and excipients. Moreover, TEM image of displayed spherical shape with smooth surface. In vitro drug release study exhibited 95% drug release up to 12 h which indicated suitability of formulation. Thus F4 batch formulation stored at room temperature and refrigerated conditions was found most stable while, accelerated and photostability samples were found to be most susceptible in comparison. Conclusion: The physicochemical stability of ginger oil extract was enhanced by loading it into solid lipid nanocarriers; the resulting SLNs also showed good antimicrobial potential against Klebsiella pneumonia throughout storage conditions.

Estudio de estabilidad acelerado del diagnosticador HemoCen Aerobio / Accelerated stability study of the HemoCen Aerobic diagnostician

La bacteriemia es una complicación grave de las infecciones bacterianas. Un diagnóstico temprano del microorganismo responsable permite aplicar tratamientos efectivos en menor intervalo de tiempo. Los hemocultivos son diagnosticadores clínicos diseñado para este fin. Objetivo: Realizar un estudio de estabilidad acelerado de un lote del hemocultivo HemoCen Aerobio que permita planificar su diseño en estante en condiciones reales. Métodos: Se formuló un lote del hemocultivo HemoCen Aerobio en el Centro Nacional de Biopreparados, BioCen y se envasó asépticamente en los Laboratorios Biológicos Farmacéuticos, LABIOFAM. Se llevó a cabo un estudio de estabilidad acelerado por el Método de Arrenhius. Los frascos se conservaron durante 120 días a 15 °C, 30 °C y 50 °C. Se realizaron evaluaciones físico-químicas, organolépticas y capacidad de promoción de crecimiento de Staphylococcus aureus ATCC 25923 a los 7, 15, 30, 60 y 120 días. Resultados: El estudio de estabilidad demostró que el pH y el color del medio se deterioran progresivamente en el tiempo cuando las temperaturas aumentan entre 30 °C y 50 °C. La promoción de crecimiento de Staphylococcus aureus resultó favorable con índices de recuperación entre 20 y 40 UFC·frasco-1. Discusión: HemoCen Aerobio resulta funcional con un desempeño analítico satisfactorio, cuyos índices de recuperación microbiana se encuentran acorde a los valores reportados en bacteriemias de escasa magnitud. Estos resultados sientan las bases para planificar un estudio de estabilidad en estante en condiciones reales. Conclusión: Se estima un período de validez de 2 años(AU)

Bacteremia is a serious complication of bacterial infections. Early diagnosis of the causative organism allows applying appropriate treatments in a shorter time interval. Hemocultures are clinical diagnosticians designed for this purpose. Objective: Perform an accelerated stability study of a batch of HemoCen Aerobic hemoculture that allows planning its shelf designed in true conditions. Methods: A batch of HemoCen Aerobic hemoculture was formulated at the National Bioproducts Center, BioCen, and aseptically packaged at the Biological Pharmaceutical Laboratories, LABIOFAM. An accelerated stability study was carried out by the Arrenhius Method. The bottles were stored for 120 days at 15 °C, 30 °C and 50 °C. Physicochemical, organoleptic and growth promotion capacity evaluations of Staphylococcus aureus ATCC 25923 were realized at 7, 15, 30, 60 and 120 days. Results: The stability study demonstrated that the pH and the color of the medium progressively deteriorate over time as temperatures increase between 30 °C and 50 °C. Growth promotion of Staphylococcus aureus was favorable with recovery rates between 20 and 40 CFU bottle-1. Discussion: HemoCen Aerobic is functional with a satisfactory analytical performance, which recovery rates are consistent with the values reported in bacteremia of low magnitude. These results provide the basis for planning a shelf stability study under real conditions. Conclusion: A durability period of 2 years was estimated(AU)

Study on quality stability of Chinese materia medica lotion for infant bronchitis / 中草药

Objective: Through the accelerated experiment and long-term experiment, the main contents of ephedrine and white peony root in Chinese materia medica (CMM) lotion were taken as the main indexes, and the stability of the medicine lotion of infants with bronchitis was investigated. Methods: According to the quality standard of CMM lotion for infant bronchitis, the existence of Ephedrae Herba, Poria, Paeoniae Radix Alba, Aurantii Fructus and Epimedii Folium in the sample was identified by thin layer chromatography. The contents of Ephedrae Herba (ephedra hydrochloride and pseudoephedrine hydrochloride) and Paeoniae Radix Alba (paeoniflorin) were determined by HPLC, and the stability of CMM lotion samples was evaluated by plate method. Results: The contents of Ephedrae Herba, Poria, Paeoniae Radix Alba, Aurantii Fructus, and Epimedii Folium were measured. The contents of Ephedrae Herba and Paeoniae Radix Alba were higher than 0.18 mg and 0.72 mg; The total contents of aerobic bacteria and mycorrhizal yeasts were not more than 100 cfu/mL, and Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were not detected, in line with quality standards. Conclusion: The three batches of CMM lotion prepared by the First People’s Hospital of Guangxi have good stability and long-term stability, for the goods packaging, transportation, and storage conditions to provide the necessary information.

A stability-indicating LC–MS/MS method for zidovudine: Identification, characterization and toxicity prediction of two major acid degradation products / 药物分析学报

Zidvovudine (AZT) is a nucleoside analogue reverse transcriptase inhibitor (NRTI), a class of anti-retroviral drug. A stability-indicating assay method for AZT was developed in line with ICH guideline. Successful separation of AZT and its degradation products was achieved by gradient elution mode on reverse phase C18 column using 10 mM ammonium acetate: acetonitrile as the mobile phase at 0.8 mL/min flow rate, 25 μL injection volume, 30 °C column temperature and 285 nm detection wavelength. Two major acid degradation products were identified and characterized by liquid chromatography–electrospray ionization mass spectro-metry (LC–ESI/MS/MS) and accurate mass measurements. The probable mechanisms for the formation of degradation products were identified based on a comparison of the fragmentation pattern of the [M + H] + ions of AZT and its degradation products. One of the degradation products, DP-1, was isolated by semi-preparative high performance liquid chromatography (HPLC) using Waters XBridge Prep C18 (250 mm×10 mm, 5 μm). Degradation products showed higher toxicity compared to the drug in some models assessed by TOPKAT software. The method validation was performed with respect to robustness, specificity, linearity, precision and accuracy as per ICH guideline Q2 (R1).

Liposomes as potential carriers for ketorolac ophthalmic delivery: formulation and stability issues / Liposomes as potential carriers for ketorolac ophthalmic delivery: formulation and stability issues

ABSTRACT Drug delivery to treat ocular disorders locally is a challenging endeavor. Traditional ocular dosage form - eye drops - exhibits poor availability, consequently inefficient therapeutic response. The objective of the study was to formulate and characterize a ketorolac tromethamine ocular system with a prolonged release pattern based on liposomes as a vesicular carrier and to design once daily liquid preparation realizing the thermal in situ gelation principle. Liposomes were prepared by film hydration method. The influence of cholesterol concentration, pH and volume of hydration medium, and type and concentration of charging imparting agents were studied. Liposomes were characterized via, morphological examination, vesicular size, and encapsulation efficiency, and in vitro release performance, moreover its stability was assessed. The results obtained highlighted that liposomes showed a closed vesicular multi-lamellar structure. Ketorolac was successfully encapsulated within the liposomal structure in a cholesterol and charge inducing agent concentration-dependent behaviour. The dispersion of liposomes within thermosensitive Poloxamer in situ gel was able to retard the release of the drug by diffusion providing a controlled prolonged delivery. The liposomal formulations were physically stable for six months. Ketorolac tromethamine in situ liposomal gel representing an efficient alternative in terms of ocular retention and patient compliance when compared with conventional eye drops.

Chemical degradation kinetics of fibrates: bezafibrate, ciprofibrate and fenofibrate

ABSTRACT Fibrates are drugs used for the treatment of hypertriglyceridemia and for the prevention of atherosclerosis. Three drugs in the fibrate class, ciprofibrate, fenofibrate and bezafibrate, were chosen for this study because their raw materials are readily available and because scientific publications on these compounds is limited. To evaluate their intrinsic stability, the drugs were exposed to a test condition (temperature, oxidation, UV light exposure, hydrolysis at different pH values and metal ions in solution) and then were subjected to analysis by HPLC. The samples were run on a C18 column, with a flow rate of 1.0 mL min-1 in a mobile phase consisting of methanol: 0.01 % phosphoric acid v/v (80:20), with variable detection wavelengths in the UV spectra. The analysis methodology showed satisfactory performance parameters. The three drugs were very unstable, degrading in each of the conditions evaluated. The test conditions of acid and basic hydrolysis showed the most significant degradation. The results demonstrated that the drugs in this class are unstable. Based on these experimentally determined degradation kinetics, it is easy to understand and emphasize the importance of the lack of liquid dosage forms on the market for fibrates because of their instability.

Estabilidad de una formulación de adrenalina 1 mg/mL inyectable, para uso veterinario / Stability of a formulation of 1mg/ml adrenaline injectable product for veterinary use

Introducción: el inyectable de adrenalina 1 mg/mL se emplea en bovinos, equinos, caprinos, ovinos, porcinos, perros y gatos como estimulante directo del miocardio, en el shock anafiláctico, el espasmo bronquial por su acción broncodilatadora, en anestesia local para prolongar su acción, como hemostático local en hemorragias superficiales, en urticaria y descongestivo conjuntival. Objetivo: evaluar el desempeño del método analítico por cromatografía líquida de alta resolución, aplicable al control de la calidad y al estudio de estabilidad del inyectable y su estabilidad en el tiempo. Métodos: la separación para cuantificar el principio activo en el producto terminado se realizó a través de una columna cromatográfica Lichrosorb RP- 18(5 µm) (250 x 4 mm), con detección ultravioleta a 280 nm, empleando una fase móvil compuesta por metanol‒solución de fosfato de sodio monobásico 0,05 M, 1‒octanosulfonato de sodio y edetato de sodio a pH 3,58 (3:17) y la cuantificación de este frente a una muestra de referencia con el método del estándar externo. El estudio de vida de estante se desarrolló por un periodo de doce meses a temperatura ambiente y el de estabilidad acelerada a 40 0 C durante seis meses. Resultados: los resultados obtenidos de los parámetros analizados en la evaluación del desempeño del método se encontraron dentro de los límites establecidos. Los resultados del estudio de estabilidad por vida de estante después de transcurridos los doce meses indicaron que el producto mantiene los parámetros que determinan su calidad durante ese tiempo y no se observó degradación significativa del producto en los estudios acelerados. Conclusiones: la evaluación del desempeño del método analítico desarrollado demostró la confiabilidad del mismo. Se estableció un año como fecha de vencimiento en las condiciones señaladas(AU)

Introduction: one mig/ml adrenaline injectable product is used in bovines, horses, caprine, ovines, swines, dogs and cats as direct myocardial stimulant in the anaphylactic shock, bronchial spasm because of its bronchodilating action, in local anesthesia to extend its action, local hemostatic agent in superficial hemorrhages, in urticaria and as conjunctival decongestive agent. Objective: to evaluate the high performance liquid chromatography analytical method applicable to the quality control and the stability study of the injectable and its time stability. Methods: for quantification of the active principle in the final product, the separation was performed with a chromatographic columm Lichosorb RP-18(5 µm) (250 x 4mm)and ultraviolect detection at 280nm, using a mobile phase of methanol-monobasic sodium phosphate 0.05 M, 1-sodium octanosulphonate and sodium edentate solution at pH 3.58 (3:17) and the quantification against a reference sample was made with the external standard method. The shelf life study was conducted for 12 months at room temperature and that of accelerated stability at 40°C for six months. Results: the achieved results in the parameters analyzed in the evaluation of the method performance were within the set limits. The results of the shelf life stability study after 12 months indicated that the product keep the parameters that determine its quality during that time and no significant degradation of the product was observed in the accelerated studies. Conclusions: the evaluation of the analytical method performance showed the reliability of the method. The expiry date was then set as one year under the stated conditions(AU)

Estabilidad de una formulación de ciclopentolato 1 por ciento colirio / Stability of a formulation of 1 percent cyclopentolate eye drops

Introducción: el colirio de ciclopentolato al 1 por ciento, se indica para medir los errores de la refracción, producir cicloplejía en procedimientos diagnósticos y también midriasis preoperatoria y postoperatoria, en el tratamiento de la uveítis y en los estados inflamatorios del iris. Objetivo: evaluar el desempeño del método de cromatografía líquida de alta resolución, aplicable al control de la calidad y estudio de estabilidad del colirio. Métodos: para cuantificar el ingrediente farmacéutico activo en el producto terminado, se empleó el método descrito en la Farmacopea de los Estados Unidos (USP 32, 2009). El estudio de vida de estante se desarrolló por un periodo de 24 meses a temperatura controlada entre 15-25 °C; mientras que el de estabilidad acelerada a 40 ± 2 °C y 75 ± 5 por ciento de humedad relativa, durante 6 meses. Resultados: los resultados obtenidos en la evaluación del desempeño del método analítico se encontraron dentro de los límites establecidos. Los resultados del estudio de estabilidad por vida de estante después de transcurridos los 24 meses indicaron que el producto mantiene los parámetros que determinan su calidad durante ese tiempo, y en los acelerados no se observó degradación significativa del producto. Conclusiones: la evaluación del desempeño del método analítico evaluado por cromatografía líquida de alta resolución demostró la confiabilidad del mismo. Se estableció 2 años como fecha de vencimiento en las condiciones señaladas(AU)

Introduction: the 1 percent cyclopentolate eye drops is indicated to measure the refractive errors, to cause cycloplexy in diagnostic procedures and also preoperative and postoperative midriasis in treating uveitis and in inflammatory conditions of the iris. Objective: to evaluate the performance of a high performance liquid chromatography applicable to the quality control and the study of the eye drops stability. Methods: with the purpose of quantifying the active ingredient in the finished product, the method described in the US Pharmacopea (USP 32,2009) was used. The shelf life study was conducted for 24 months at controlled 15-25 ºC temperature whereas the study of accelerated stability at40±2 ºC and 75± 5 percent relative humidity lasted 6 months. Results: the achieved results in the evaluation of the performance of the analytical method were within the set limits. The results for the shelf life stability after 24 months yielded that the product keeps the quality parameters during this time and in the accelerated stability study, there was no sign of significant degradation. Conclusions: the evaluation of the performance of the analytical method based on high performance liquid chromatography showed its reliability. The expiry date was set at 2 years under the stated conditions(AU)

Stability-indicating liquid chromatographic and UV spectrophotometric methods for the quantification of ciprofibrate in capsules and tablets

This study describes the development and evaluation of stability-indicating liquid chromatographic (LC) and UV spectrophotometric methods for the quantification of ciprofibrate (CPF) in tablets and capsules. Isocratic LC separation was achieved on a RP18 column using a mobile phase of o-phosphoric acid (0.1% v/v), adjusted to pH 3.0 with triethylamine (10% v/v) and acetonitrile (35:65 v/v), with a flow rate of 1.0 mL min-1. Detection was achieved with a photodiode array detector at 233 nm. For the spectrophotometric analysis, ethanol and water were used as the solvent and a wavelength of 233 nm was selected for the detection. The methods were validated according to International Conference on Harmonization (ICH) guidelines for validating analytical procedures. Statistical analysis showed no significant difference between the results obtained by the two methods. The proposed methods were successfully applied to the CPF quality-control analysis of tablets and capsules.

Este estudo descreve o desenvolvimento e avaliação de método indicativo da estabilidade por cromatografia líquida (LC) e método por espectrofotometria UV para quantificação de ciprofibrato (CPF) em comprimidos e cápsulas. No método por cromatografia líquida as análises foram realizadas isocraticamente em coluna de fase reversa C18, utilizando fase móvel composta por ácido o-fosfórico (0.1% v/v) pH 3.0, ajustado com trietilamina (10% v/v), e acetonitrila (35:65 v/v), com fluxo de 1,0 mL min-1. A detecção foi realizada em detector de arranjo de diodos a 233 nm. Na análise espectrofotométrica, etanol e água foram utilizados como solventes e o comprimento de onda de 233 nm foi selecionado para a detecção do fármaco. Os métodos foram validados de acordo com as diretrizes do International Conference on Harmonization (ICH). A análise estatística não mostrou diferença significativa entre os resultados obtidos pelos dois métodos. Os métodos foram aplicados com sucesso para análises de controle de qualidade do ciprofibrato em comprimidos e cápsulas.

Stability study of oseltamivir phosphate capsules / 中国药学杂志

METHODS: HPLC method was used to study the stability of sixteen batches of oseltamivir phosphate capsules. Phenomenex C8 (2) column was used with UV detection at 207 nm, and the mobile phase consisted of phosphoric buffer (0.05 mol•L-1 KH2PO4), methanol and acetonitrile (620:135:245), the flow rate was 1.0 mL•min-1, and the column oven was maintained at 50°C. The contents of impurities before and after storage and in accelerated condition were tracked.

Characterization and stability studies of emulsion systems containing pumice

Emulsions are the most common form of skin care products. However, these systems may exhibit some instability. Therefore, when developing emulsions for topical application it is interesting to verify whether they have suitable physical and mechanical characteristics and further assess their stability. The aim of this work was to study the stability of emulsion systems, which varied in the proportion of the emulsifying agent cetearyl alcohol (and) sodium lauryl sulfate (and) sodium cetearyl sulfate (LSX), the nature of the oily phase (decyl oleate, cyclomethicone or dimethicone) and the presence or absence of pumice (5% w/w). While maintaining the samples at room temperature, rheology studies, texture analysis and microscopic observation of formulations with and without pumice were performed. Samples were also submitted to an accelerated stability study by centrifugation and to a thermal stress test. Through the testing, it was found that the amount of emulsifying agent affects the consistency and textural properties such as firmness and adhesiveness. So, formulations containing LSX (5% w/w) and decyl oleate or dimethicone as oily phase had a better consistency and remained stable with time, so exhibited the best features to be used for skin care products.

Emulsões são a forma de apresentação mais comum dos produtos para aplicação na pele. No entanto estes sistemas podem exibir alguma instabilidade. Por esta razão, quando do desenvolvimento de emulsões para aplicação tópica é importante verificar se estas apresentam propriedades físicas ou mecânicas adequadas e avaliar a sua estabilidade. O objetivo deste trabalho consistiu no estudo da estabilidade de emulsões, cujas variações entre elas foi a proporção de agente emulsificante álcool estearílico (mais) laurilsulfato de sódio (mais) estearilsulfato de sódio (LSX), a natureza da fase oleosa (decil oleato, ciclometicona ou dimeticona) e a presença ou ausência de pedra-pomes (5% m/m). Mantendo as amostras à mesma temperatura, realizaram-se o estudo da reologia, a análise de textura e observação microscópica das formulações com e sem pedra-pomes. Amostras foram, também, submetidas a estudo de estabilidade acelerada por centrifugação e a ensaio de estresse térmico. Através dos testes realizados, constatou-se que a quantidade de agente emulsificante influencia a consistência e as propriedades de textura, como a firmeza e a adesividade. As formulações contendo LSX (5% m/m) e decil oleato ou dimeticona como fase oleosa exibiram melhores caraterísticas como produtos para aplicação na pele, uma vez que estas formulações apresentaram menor firmeza e consistência e permaneceram estáveis com o tempo.

Application of capillary electrophoresis to the simultaneous determination and stability study of four extensively used penicillin derivatives

The applicability of capillary electrophoresis for the analysis of four extensively used penicillin derivatives (benzylpenicillin, ampicillin, amoxicillin, oxacilllin) has been studied. Because of structural similarities, the electrophoretic behavior of these derivatives is very similar; consequently an efficient separation using the conventional capillary zone electrophoresis is hard to be achieved. Their simultaneous separation was solved by using micellar electrokinetic capillary chromatography, the separation being based on the differential partition of the analytes between the micellar and aqueous phase. Using a buffer solution containing 25 mM sodium tetraborate and 100 mM sodium dodecyl sulfate as surfactant, at a pH of 9.3, applying a voltage of + 25 kV at a temperature of 25 °C, we achieved the simultaneous separation of the studied penicillin derivatives in less then 5 minutes. The separation conditions were optimized and the analytical performance of the method was evaluated in terms of precision, linearity, limit of detection, and quantification. Also, a simple capillary zone electrophoresis method was applied to study the stability of the studied penicillin derivatives in water at different temperatures, using ciprofloxacin hydrochloride as internal standard. It was observed that the extent of the hydrolysis of penicillins in water is highly dependent on the time and also temperature.

Estudou-se a aplicabilidade de electroforese capilar para a análise de quatro derivados de penicilina (benzilpenicilina, ampicilina, amoxicilina, oxacilina) amplamente utilizados. Em razão das semelhanças estruturais, o comportamento electroforético destes derivados é muito semelhante e, por conseguinte, a separação eficaz utilizando a electroforese capilar de zona convencional é difícil de ser efetuada. A separação simultânea foi realizada por cromatografia capilar electrocinética micelar, que se baseia na partição diferencial entre os analitos na fase micelar e aquosa. Utilizando-se solução tampão contendo 25 mM de tetraborato de sódio e 100 mM de dodecil sulfato de sódio, como agente tensioativo, com pH de 9,3, voltagem de +25 kV, à temperatura de 25 °C, obteve-se a separação simultânea das penicilinas estudadas em menos de 5 minutos. As condições de separação foram otimizadas e o desempenho do método analítico foi avaliado em termos de precisão, linearidade, limite de detecção e de quantificação. Além disso, aplicou-se método de electroforese capilar de zona simples para estudar a estabilidade de penicilinas em água a diferentes temperaturas, utilizando cloridrato de ciprofloxacino como padrão interno. Estabeleceu-se que o grau de hidrólise de penicilinas em água é altamente dependente do tempo e também da temperatura.

Formulation and characterization of gastroretentive drug delivery system of losartan potassium.

Floating matrix tablets of losartan potassium were developed with an aim to prolong its gastric residence time and increase the bioavailability of drug. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The tablets were prepared by wet granulation technique, using polymers Methocel K15 and Methocel K100 in combination with other standard excipients. Sodium bicarbonate was incorporated as gas generating agent. The effects of sodium bicarbonate and polymers on drug release profile and floating properties were investigated. It was found that viscosity of Methocel K15 and Methocel K100 along with sodium bicarbonate had significant impact on the release and floating properties of the delivery system. The decrease in the release rate was observed with an increase in the viscosity of the polymeric system. Polymer with high viscosity Methocel K100 was shown to be beneficial than low viscosity polymer Methocel K15 in improving the floating properties of gastric floating drug delivery system (GFDDS). The observed difference in the drug release and floating properties of GFDDS could be attributed to the difference in the basic properties of two polymers, Methocel K15 and Methocel K100 due to their water uptake potential and functional group substitution. The release mechanism were explored and described with zero-order, first-order and Korsmeyer-Peppas equations. The drug release profiles and buoyancy of the floating tablets were stable when stored at 40°C/75% RH for 6 months.

Formulation and characterization of gastroretentive drug delivery system of losartan potassium.

Floating matrix tablets of losartan potassium were developed with an aim to prolong its gastric residence time and increase the bioavailability of drug. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The tablets were prepared by wet granulation technique, using polymers Methocel K15 and Methocel K100 in combination with other standard excipients. Sodium bicarbonate was incorporated as gas generating agent. The effects of sodium bicarbonate and polymers on drug release profile and floating properties were investigated. It was found that viscosity of Methocel K15 and Methocel K100 along with sodium bicarbonate had significant impact on the release and floating properties of the delivery system. The decrease in the release rate was observed with an increase in the viscosity of the polymeric system. Polymer with high viscosity Methocel K100 was shown to be beneficial than low viscosity polymer Methocel K15 in improving the floating properties of gastric floating drug delivery system (GFDDS). The observed difference in the drug release and floating properties of GFDDS could be attributed to the difference in the basic properties of two polymers, Methocel K15 and Methocel K100 due to their water uptake potential and functional group substitution. The release mechanism were explored and described with zero-order, first-order and Korsmeyer-Peppas equations. The drug release profiles and buoyancy of the floating tablets were stable when stored at 40°C/75% RH for 6 months.

Formulation and evaluation of Salbutamol sulphate microspheres by solvent evaporation method.

Salbutamol sulphate (SS) loaded microspheres were prepared by solvent evaporation method with combination of hydroxy propyl methyl cellulose and Carbopol polymers in various proportions. A total of eleven formulations were prepared i.e. E1, E2, E3, E4, E5, E6, E7, E8, E9, E10 and E11.The particle size of all the formulations were ranged between 110±0.02 and 183±0.02μm. The entrapment efficiency was ranged between 68.3±0.01 and 94.9±0.02%. Based on above parameters four formulations were selected i.e. E5, E8, E9 and E10 for further studies like micromeretic properties, swelling index and in-vitro release profile. It was confirmed with the results of micromeretic property that all the selected formulations showed good flow property. Release data were analyzed based on Highuchi kinetics and Korsmeyer-Peppas equation and all the selected formulations showed good fit to Highuchi model. Stability studies showed almost negligible changes in particle size, entrapment efficiency and drug release throughout the study period.

Technological development and stability study of meprobamate immediate released tablets

The behavior of different technological variants of fast release tablets of Meprobamato (400 mg) obtained by wet granulation. The desintegration time and the percentage of the dissolved drug showed a significant dependence of the sodium lauryl sulfate /sodium croscarmelose ratios present in formulae. The physical and chemical properties of tablets were assessed during 6 months (accelerated stability and dring 24 months (useful life), respectively. From the formulae selected it was possible to obtain granulates and tablets with organoleptic, physicomechanical and technological properties, demonstrating the feasibility of the process of fabrication of this product. Results showed the good stability in the immediate release of Meprobamato tablets selected. The in vitro dissolution hasn't significant differences, thus, neither the time elapsed nor the composition of formula inluenced on the percentages of dissolved drug. The assessment demonstrated significant differences, however, assessed formulae fulfilled with official pharmaceutical specifications during 24 months

Se estudió el comportamiento de diferentes variantes tecnológicas de tabletas de liberación inmediata de meprobamato (400 mg), obtenidas por granulación húmeda. El tiempo de desintegración y el porcentaje de fármaco disuelto mostraron dependencia significativa con las proporciones del lauril sulfato de sodio/croscarmelosa sódica en las formulaciones. Se evaluaron las propiedades físicas y químicas de las tabletas durante 6 meses (estabilidad acelerada) y 24 meses (de vida útil), respectivamente. Se obtuvieron a partir de las formulaciones seleccionadas granulados y tabletas con propiedades organolépticas, físico-mecánicas y tecnológicas satisfactorias, lo que indicó la factibilidad del proceso de fabricación de este producto. Los resultados demostraron la buena estabilidad de las formulaciones de tabletas de liberación inmediata de meprobamato seleccionadas. La disolución in vitro no mostró diferencias significativas, por lo que ni el tiempo transcurrido ni la composición de la formulación influyeron sobre los porcentajes del fármaco disuelto. La valoración mostró diferencias significativas, sin embargo, las formulaciones evaluadas cumplieron con las especificaciones farmacéuticas oficiales durante 24 meses

Desarrollo tecnológico de una formulación de cloruro de sodio al 5 por ciento para el tratamiento del edema corneal en Cuba / Technological development of a 5 percent sodium chloride formula for treatment of corneal edema in Cuba

Se desarrolló una formulación para uso oftálmico, que contenía cloruro de sodio al 5 por ciento, estable desde el punto de vista físico, químico y microbiológico. Se realizaron los estudios de formulación correspondientes, seleccionándose la composición y procedimiento tecnológico más adecuados. Además, se estudió la efectividad antimicrobiana de los preservativos antimicrobianos empleados según se establece en la Farmacopea de los Estados Unidos 30 y se comprobó la seguridad del uso de este medicamento a través de los resultados del ensayo de irritabilidad oftálmica. Se elaboraron 3 lotes del medicamento y se envasaron en frascos plásticos de polietileno de baja densidad con tapa de polipropileno de alta densidad y se almacenaron a temperatura ambiente durante 24 meses; se estudió su estabilidad física y química por el método acelerado y de vida de estante. Se comprobó su estabilidad microbiológica a cada uno de los lotes elaborados, al inicio y final del estudio, según se establece en la Farmacopea de los Estados Unidos 30, y se obtuvieron resultados satisfactorios. Todos los resultados cumplieron con los límites de calidad establecidos en la literatura oficial para este tipo de forma farmacéutica, por lo que se concluyó que el medicamento desarrollado está correctamente formulado desde el punto de vista galénico con un tiempo de vida útil de 24 meses almacenado bajo las condiciones estudiadas, demostrado según el otorgamiento del certificado de registro por el organismo regulador (Centro Estatal para el Control de Medicamentos, CECMED). Finalmente el medicamento fue introducido al nivel industrial sin que se presentaran problemas tecnológicos

A formula for ophthalmic use was developed containing 5 percent sodium chloride stable from the physical, chemical and microbiological point of view. Studies of corresponding formulae were conducted selecting the more suitable composition and technological procedure. Also, the antimicrobial effectiveness of animicrobials preservatives used according to United States Pharmacopeia was studied demonstrating the safe use of this drug by the results of the ophthalmic irritability trial. Three batchs of this drug were elaborated packing in low density polyethylene plastic flasks with a high density polypropylene top stored at room temperature during 24 monhts and its physical and cchemical stability was studied y accelerated method and of shield-life. At onset and the end of study microbiological stability was demonstrate in each of batches made (30), according to USP with satisfactory results. All results fulfill with the established quality limits in official literature for this type of pharmaceutical way concluding that this developeddrug is appropriately formulated fro the doctoral point of view with a useful life time of 24 months stored under study conditions, demonstrated according to award of registry certificate by regulator institution (State Center for Drugs' Control, CECMED). Finally, the drug was introduced at industrial level without technological problems

Validación de la técnica para la determinación de catequina en tabletas de Rhizophora mangle L por CLAR / Validation of the technique to assessment of tablets Catechin from Rhizophora mangle L by HPLC

Se realizó la validación del método de cromatografía líquida de alta resolución para la determinación cuantitativa de catequina como sustancia marcador en las tabletas obtenidas a partir del extracto seco de las cortezas de Rhizophora mangle L, empleadas en el tratamiento de úlceras gastroduodenales. Considerando que el método se clasifica como tal para la determinación cuantitativa del compuesto mayoritario o ingrediente activo en formulaciones o materia prima, se evaluaron los parámetros: especificidad, linealidad, exactitud, sensibilidad y precisión expresada en sus 2 formas: repetibilidad y precisión intermedia. Los resultados obtenidos demostraron que el método empleado es confiable, pues permitió la determinación del compuesto en presencia de otras sustancias, incluyendo excipientes y sustancias auxiliares, y detectó la presencia de productos de degradación. Además, el procesamiento estadístico de los resultados evidenció la linealidad, precisión, sensibilidad y exactitud del método.

Authors made the high-performance liquid chromatography method validation to the quantitative assessment of cathechin as a marker substance in tablets obtained from the bark of Rhizophora mangle L dry extract used in gastroduodenal ulcers treatment. Considering that this method as such is classified to quantitative assessment of the major compound or active ingredient in formulae or raw material, the following parameters were assessed : linearity, accuracy, sensitivity and precision expressed in its two ways: repetition and intermediate precision. Results obtained showed that this method is reliable allowing the compound assessment in presence of other substances, including excipients and auxilliary substances and to detect the presence of degradation products. Also, the statistical processing of results evidenced the linearity, precision, sensitivity and accuracy of this method.