Estabilidade do cloridrato de vancomicina empregado em soluções de selo antimicrobiano de cateteres intravenosos centrais / Stability of vancomycin hydrochloride employed in antimicrobial seal solutions of central intravenous catheters / Estabilidad del clorhidrato de vancomicina utilizado en soluciones de sellado antimicrobiano para catéteres intravenosos centrales

Resumo Objetivo: verificar a estabilidade do cloridrato de vancomicina em soluções de selo antimicrobiano sem e com associação de heparina sódica segundo a temperatura e tempo de associação. Método: estudo experimental delineado para análise de potencial hidrogeniônico e concentração por cromatografia líquida de alta eficiência de soluções de cloridrato de vancomicina (n=06) e cloridrato de vancomicina e heparina sódica (n=06). Submeteram-se as soluções estudadas à ausência de luz, 22°C e 37°C. Análises em triplicadas (n=192) ocorreram no momento inicial (T0), três (T3), oito (T8) e 24 horas (T24) após preparo. Os dados foram submetidos à análise de variância (p≤0,05). Resultados: a concentração do antimicrobiano a 22°C apresentou redução (T0-T8) e posterior elevação (T24); o potencial hidrogeniônico diminuiu significativamente ao longo do tempo. Em 37°C a concentração aumentou em até T3 e reduziu em T24, com redução de potencial hidrogeniônico até 24 horas. A concentração das soluções de cloridrato de vancomicina e heparina sódica apresentaram variação com redução a 22°C acompanhada de aumento de potencial hidrogeniônico. Observou-se formação de precipitado por inspeção visual da associação cloridrato de vancomicina e heparina sódica (T3). Conclusão: evidenciou-se estabilidade farmacológica do cloridrato de vancomicina (5 mg/mL) e incompatibilidade física com heparina sódica (100 UI/mL) após três horas de associação nas soluções de selo antimicrobiano estudadas.

Abstract Objective: to verify the stability of vancomycin hydrochloride in antimicrobial seal solutions with and without association of heparin sodium according to temperature and association time. Method: an experimental study designed for the analysis of hydrogenionic potential and concentration by means of high-efficiency liquid chromatography of vancomycin hydrochloride (n=06) and vancomycin hydrochloride and heparin sodium (n=06). The solutions studied were submitted to absence of light, as well as to 22°C and 37°C. Analyses in triplicate (n=192) were performed at the initial moment (T0) and three (T3), eight (T8) and 24 hours (T24) after preparation. The data were submitted to analysis of variance (p≤0.05). Results: concentration of the antimicrobial at 22°C presented a reduction (T0-T8) and a subsequent increase (T24); hydrogenionic potential decreased significantly over time. At 37°C, the concentration increased up to T3 and decreased at T24, with a reduction of hydrogenionic potential up to 24 hours. Concentration of the vancomycin hydrochloride and heparin sodium solutions varied with a reduction at 22°C, accompanied by increased hydrogenionic potential. Precipitate formation was observed by visual inspection of the vancomycin hydrochloride-heparin sodium association (T3). Conclusion: pharmacological stability of vancomycin hydrochloride (5 mg/mL) and physical incompatibility with heparin sodium (100 IU/mL) were evidenced after three hours of association in the antimicrobial seal solutions studied.

Resumen Objetivo: verificar la estabilidad del clorhidrato de vancomicina en soluciones de sellado antimicrobiano solo y combinado con heparina sódica según la temperatura y el tiempo de combinación. Método: estudio experimental diseñado para analizar el potencial de hidrógeno y la concentración por cromatografía líquida de alta resolución de soluciones de clorhidrato de vancomicina (n=06) y de clorhidrato de vancomicina y heparina sódica (n=06). Las soluciones estudiadas fueron sometidas a ausencia de luz, 22°C y 37°C. Se realizaron análisis por triplicado (n=192) en el momento inicial (T0), a las tres (T3), ocho (T8) y 24 horas (T24) después de la preparación. Los datos fueron sometidos a análisis de varianza (p≤0,05). Resultados: la concentración de antimicrobiano a 22°C mostró una reducción (T0-T8) y un posterior aumento (T24); el potencial de hidrógeno disminuyó significativamente con el tiempo. A 37°C, la concentración aumentó hasta T3 y disminuyó en T24, el potencial de hidrógeno disminuyó hasta las 24 horas. La concentración de las soluciones de clorhidrato de vancomicina y heparina sódica mostró variación con la reducción a 22°C acompañada de un aumento del potencial de hidrógeno. Mediante inspección visual se observó la formación de un precipitado al combinar clorhidrato de vancomicina y heparina sódica (T3). Conclusión: el clorhidrato de vancomicina (5 mg/ml) presentó evidencia de estabilidad farmacológica e incompatibilidad física con la heparina sódica (100 UI/ml) después de las tres horas de haberse realizado la combinación en las soluciones de sellado antimicrobiano estudiadas.

Captopril oral solution for pediatric use: formulation, stability study and palatability assessment in vivo

Abstract he aim of this work was to develop an oral solution of captopril at 5 mg/mL preservative-free. Two formulations were prepared, one containing sweetener (formulation 1) and the other without this excipient (formulation 2). The results found of validation parameters from analytical method performed by HPLC for captopril were, linearity 0.9998, the limit of detection 15.71 µg/mL, the limit of quantification 47.60 µg/mL, repeatability 1.05%, intermediate precision 2.42%, accuracy intraday 101,53%, accuracy inter-day 99.85%. Moreover, the results found for captopril disulfide were, linearity 0.9999, limit of detection 0.65 µg/mL, limit of quantification 1.96 µg/mL, repeatability 2.28%, intermediate precision 1.51%, accuracy intraday 101.36%, accuracy inter-day 100.29%. The appearance of formulations was clear and colorless, pH measures were 3.12 and 3.04, dosage of captopril and captopril disulfide were 99.45% and 99.82%, 0.24% and 0.12% for formulation 1 and formulation 2, respectively. The stability study demonstrated that the concentration of captopril and captopril disulfide in the formulations was > 90% and below 3%, respectively. The in vivo palatability study in animals and humans showed that Formulation 1 containing the sweetener had better acceptance. Thus, the sweetener was able to improve the unpleasant taste of the formulation

Co-amorphous technology to improve dissolution and physical stability of silybin / 中国中药杂志

The present study explored the effect of co-amorphous technology in improving the dissolution rate and stability of silybin based on the puerarin-silybin co-amorphous system prepared by the spray-drying method. Solid-state characterization was carried out by powder X-ray diffraction(PXRD), polarizing microscopy(PLM), Fourier transform infrared spectroscopy(FT-IR), differential scanning calorimetry(DSC), etc. Saturated powder dissolution, intrinsic dissolution rate, moisture absorption, and stability were further investigated. The results showed that puerarin and silybin formed a co-amorphous system at a single glass transition temperature which was higher than that of any crude drug. The intrinsic dissolution rate and supersaturated powder dissolution of silybin in the co-amorphous system were higher than those of the crude drug and amorphous system. The co-amorphous system kept stable for as long as three months under the condition of 40 ℃, 75% relative humidity, which was longer than that of the single amorphous silybin. Therefore, the co-amorphous technology could significantly improve the dissolution and stability of silybin.

Evaluation of physicochemical and microbiological stability of liquid preparation from tizanidine hydrochloride tablets - a Hospital concern

Tizanidine hydrochloride is a centrally acting skeletal muscle relaxant, used in the management of spasticity. This drug is commercially available only as tablets, which highlights the need to develop oral liquid formulations. In the hospital environment, this aspect is circumvented by the preparation of suspensions, to allow administration to children and adults with impaired swallowing, but there are no data regarding their stability. The purpose of this study was to evaluate the physicochemical andmicrobiological stability of liquid dosage forms prepared in the hospital environment from tizanidine hydrochloride tablets, applying high performance liquid chromatography (HPLC) and microbiological analysis. A simple and stability-indicating HPLC method was developed and validated for specificity, linearity, limits of detection and quantification, precision, accuracy and robustness. The liquid formulations were placed in amber PET and glass bottles, which were stored under three different conditions: at room temperature, under refrigeration and at 40 ºC. The liquid formulations were analyzed and demonstrated chemical stability for 56 days, allowing their use for long periods. However, the determination of microbiological stability showed that these formulations are prone to microbial contamination, which has dramatically reduced its stability to 7 days, in both bottles and at all evaluated temperatures

Desenvolvimento de formas farmacêuticas semissólidas contendo o extrato aquoso obtido das cascas do Anacardium occidentale L. e realização do estudo de estabilidade acelerado / Development of semissolid pharmaceutical forms containing aqueous extract from the cases of Anacardium occidentale L. and implementation of the accelerated stability study / Desarrollo de formas farmacéuticas semesólidas contiene el extracto aquoso obtenido de las cascas del Anacardium occidentale L. y realización del estudio de estabilidad acelerada

Introdução: A Anacardium occidentale (cajueiro), é uma árvore tropical frutífera nativa do Brasil. Suas cascas são ricas em taninos, com ação anti-inflamatória e cicatrizante. Objetivo: Desenvolver formulações semissólidas: gel de carbopol, creme e pomada de lanovaselina contendo o extrato aquoso das cascas de Anacardium occidentale nas concentrações de 2,5 %, 5 % e 7 %, e realizar estudos de estabilidade acelerada, avaliando as características organolépticas, pH, viscosidade e densidade relativa, nos tempos T(0) na data da produção, em temperatura ambiente, e T(30), T(60) e T(90) dias em estufa à 40ºC , afim de determinar a formulação mais estável. Resultados e conclusões: A formulação de creme apresentou melhor estabilidade em todas as concentrações do extrato e quanto a todos os parâmetros avaliados, no entanto, é necessário um estudo posterior para a padronização das formulações.(AU)

Introduction: The Anacardium occidentale (cashew tree) is a tropical fruit tree native to Brazil. Their peels are rich in tannins, with anti-inflammatory and healing action. Aim: To develop semi-solid formulations: carbopol gel, cream and ointment containing the aqueous extract of the barks of Anacardium occidentale at concentrations of 2.5%, 5% and 7%, and to perform accelerated stability studies, evaluating the organoleptic characteristics, pH, viscosity and relative density, at T (0) times at the production date, at room temperature, and T (30), T (60) and T (90) days at 40ºC in order to determine the most stable. Results and conclusions: The cream formulation presented better stability at all concentrations of the extract and for all the evaluated parameters, however, a further study is necessary for the standardization of the formulations.(AU)

Introducción: el Anacardium occidentale (anacardo) es un árbol frutal tropical originario de Brasil. Sus cáscaras son ricas en taninos, con acción antiinflamatoria y curativa. Objetivo: Desarrollar formulaciones semisólidas: gel de carbopol, crema y pomada que contengan el extracto acuoso de las cortezas de Anacardium occidentale en concentraciones de 2.5%, 5% y 7%, y realizar estudios de estabilidad acelerados, evaluando las características organolépticas, pH, viscosidad y densidad relativa, en T (0) veces a la fecha de producción, a temperatura ambiente, y T (30), T (60) y T (90) días a 40ºC para determinar el máximo estable Resultados y conclusiones: La formulación en crema presentó una mejor estabilidad en todas las concentraciones del extracto y para todos los parámetros evaluados, sin embargo, es necesario un estudio adicional para la estandarización de las formulaciones.(AU)

Desenvolvimento e caracterização de nanocápsulas poliméricas contendo carvacrol para inibição de Salmonella enteritidis / Development and characterization of polymeric nanocapsules containing carvacrol for inhibition from Salmonella enteritidis

Avaliou-se caracterização físico-química, ação bactericida e estabilidade de nanocápsulas poliméricas de Eudragit contendo carvacrol preparadas utilizando técnica de deposição interfacial do polímero pré-formado. As nanocápsulas apresentaram diâmetro médio de 146 nm, PDI de 0,181 e potencial zeta de + 23,44 mV e a concentração bactericida mínima necessária para inativar Salmonella Enteritidis foi de 0,331 mg/mL. A solução contendo nanocápsulas manteve suas características físico-químicas e atividade bactericida inalteradas durante os 45 dias do teste de estabilidade, demonstrando características promissoras para o desenvolvimento de um sanitizantes para uso em indústria produtora de ovos e frigorífico de aves.

Development of stability-indicating LC method assisted by Design of Experiment for fenticonazole cream analysis in presence of degradation product

Fenticonazole is an antifungal drug widely used in a cream formulation including as a generic medicine. Stability studies of fenticonazole in a cream formulation are very scarce. In this research, we intent to contribute to generic medicines quality control and provide reliable data seeking for insertion of fenticonazole monograph in official compendia. Therefore, in this work it was studied the behavior of fenticonazole under several conditions and developed a stability-indicating LC method to separate the degradation products and quantify the drug in presence of them, using the Design of Experiments (DoE) as tool to achieve robust and easy transferable method. Fenticonazole stability was evaluated under aqueous, alkaline (0.1 M NaOH), acidic (0.1 M HCL) and oxidative (3% v/v, H2O2) at ambient temperature and heating at 90°C, over 6 hours. The drug shows to be unstable under all stressed test conditions. It was completely degraded under acid medium with arising of degradation products. The robust and stability indicating LC method was validated. It is able to reveal the fenticonazole instability and to separate its degradation product with accuracy and precision (CV ˂ 2%) and without any placebo interferences.(AU)

Effect of HPMCAS/curcumin amorphous solid dispersion in enhancing dissolution and chemical stability of curcumin / 中国中药杂志

To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.

Forced degradation of gliquidone and development of validated stability-indicating HPLC and TLC methods

Forced degradation studies of gliquidone were conducted under different stress conditions. Three degradates were observed upon using HPLC and TLC and elucidated by LC-MS and IR. HPLC method was performed on C18 column using methanol-water (85:15 v/v) pH 3.5 as a mobile phase with isocratic mode at 1 mL.min-1 and detection at 225 nm. HPLC analysis was applied in range of 0.5-20 µg.mL-1 (r =1) with limit of detection (LOD) 0.177 µg.mL-1. TLC method was based on the separation of gliquidone from degradation products on silica gel TLC F254 plates using chloroform-cyclohexane-glacial acetic acid (6:3:1v/v) as a developing system with relative retardation 1.15±0.01. Densitometric measurements were achieved in range of 2 -20 µg /band at 254 nm (r = 0.9999) with LOD of 0.26 µg /band. Least squares regression analysis was applied to provide mathematical estimates of the degree of linearity. The analysis revealed a linear calibration for HPLC where a binomial relationship for TLC. Stability testing and methods validation have been evaluated according to International Conference on Harmonization guidelines. Moreover, the proposed methods were applied for the analysis of tablets and the results obtained were statistically compared with those of pharmacopeial method revealing no significant difference about accuracy and precision.

Desenvolvimento e validação de método analí­tico indicativo de estabilidade por CLAE-DAD-CAD para besilato de anlodipino e seus produtos de degradação / Development and validation of analytical method indicative of stability by HPLC-DAD-CAD for amlodipine besylate and its degradation products

O presente estudo foi realizado com o objetivo de se desenvolver e validar uma metodologia analítica indicativa de estabilidade para separação e quantificação de anlodipino e seus produtos de degradação no medicamento besilato de anlodipino 5 mg por comprimido. Para tanto, realizou-se um estudo de degradação forçada, como forma de identificar os principais produtos de degradação, que podem vir a formar num estudo de estabilidade, bem como estabelecer possíveis rotas de degradação. Foi utilizada a técnica instrumental de separação, cromatografia a líquido (CL), com dois tipos de detectores: arranjo de diodos (DAD) e corona CAD (Detector de aerossol carregado), coluna cromatográfica Zorbax SB-Phenyl 1,8µm 4,6 x 50 mm Agilent® e fase móvel constituída por tampão pH3,0, metanol e acetonitrila sob condições de gradiente (75% de tampão pH 3,0, 15% de metanol e 10% de acetonitrila; no tempo de 10 minutos tem-se 20% de tampão pH3,0, 60% de metanol e 20% de acetonitrila; no tempo de 13 minutos tem-se 75% de tampão pH3,0, 15% de metanol e 10% de acetonitrila; e no tempo de 15 minutos tem-se 75% de tampão pH3,0, 15% de metanol e 10% de acetonitrila); fluxo de 1,0mL/min até 10 minutos; de 10,1 a 13 minutos tem-se fluxo de 0,5 mL/min; e de 13,1 a 15 minutos volta ao fluxo de 1,0 mL/min; e detecção em 238 nm. O método apresentou-se linear, preciso, exato, robusto e seletivo, e proporcionou resultados confiáveis, sem interferência de degradantes e impurezas

This study was conducted in order to develop an analytical methodology indicative of stability for separation and quantification of the antihypertensive amlodipine and its degradation products in the drug amlodipine besylate 5 mg per tablet. For this development was performed a forced degradation study, in order to identify the main degradation products that may form in a stability study, as well as establish possible degradation routes. It was used the instrumental separation technique, liquid chromatography (LC) with two types of detectors: diode array (DAD) and corona CAD (Charged Aerosol Detector), chromatographic column Zorbax SB-Phenyl 4.6 x 50 mm 1,8µm Agilent® and mobile phase of buffer pH3,0, methanol and acetonitrile under gradient conditions (75% buffer pH3,0, 15% methanol and 10% acetonitrile; 10 minutes has 20% buffer pH3,0, 60% methanol and 20% acetonitrile; 13 minutes has become 75% of buffer pH3,0, 15% methanol and 10% acetonitrile; and 15 minutes has become 75% of buffer pH3,0, 15% methanol and 10% acetonitrile); flow 1.0 mL/ min up to 10 minutes; a flow 0,5 mL/min is obtained from 10,1 to 13 minutes; and from 13,1 minutes the flows returns to 1,0 mL/min; and detection in 238 nm. The method is linear, precise, accurate, robust and selective, and provided reliable results without interference from degradation products and impurities

Determination of compatibility and stability of haloperidol and morphine mixtures used in palliative care

Abstract With the aim of controlling various symptoms, possible to use mixtures of different drugs within infusion devices. This should take into account the compatibility of the mixture. Factors influence the compatibility and stability of the mixtures are: drug type, concentration, solvent, temperature and light. When evaluating the compatibility of the mixtures for infusion for subcutaneous via is important to consider infusion devices used and the conditions of light and temperature should simulate as far as possible the conditions in practice assistance. There are diverse studies that analyze the compatibility of drug mixtures, but there are still many possible combinations of drugs for which evidence is not available. The objective of this work is to study the compatibility and stability of several mixtures of haloperidol and morphine that can be used in solution for subcutaneous infusion.

Évaluation de la stabilité du cotrimoxazole 240 mg / 5 ml suspension commercialisé dans les circuits formel et informel de la ville de Douala

Introduction. Le marché parallèle de la vente des médicaments s'est développé au cours des dernières décennies dans les pays en voie d'émergence et il a été établi que la commercialisation de médicaments hors du circuit officiel est une source potentielle de risques pour la santé publique. Notre étude avait pour objectif d'étudier la stabilité du Cotrimoxazole 240 mg / 5 ml suspension stocké dans les circuits formel et informel. Méthodologie : De septembre 2015 à Mai 2016, une étude expérimentale a été conduite dans la ville de Douala. Un total de 81 échantillons de Cotrimoxazole 240 mg/5 mL suspension ont été prélevés dans neuf sites. Tous les échantillons ont subi un contrôle qualité sur la base des évaluations technico-règlementaire, organoleptique, physico-chimique et microbiologique. De plus, des analyses qualitative et quantitative des composés actifs du cotrimoxazole (sulfaméthoxazole et triméthoprime) ont été réalisées. Résultats. Le Ghana et l'Inde sont apparus comme les plus grands fournisseurs du Cotrimoxazole. Les numéros de lot, la notice, les dates de fabrication et de péremption, la présentation et la forme, la classe thérapeutique, les indications, et la posologie étaient présents sur tous les échantillons (100%). Par ailleurs, 41,99% et 55,55% des échantillons étaient de couleur ponceau et avaient un goût aromatisé à la fraise respectivement (p-value < 0,0001). Le pH moyen des suspensions de Cotrimoxazole dans le secteur informel s'est révélé significativement faible par rapport à celui des suspensions du secteur formel (p-value = 0,0054). Tous les échantillons étaient exempts de microorganismes pathogènes. L'analyse spectrophotométrique UV-Vis a montré que la teneur en substances actives était en moyenne significativement plus élevée dans le secteur formel (80,16% contre 73,16%; p-value = 0,001). Conclusion. Cette étude souligne le besoin urgent de lutter activement contre la vente illicite des médicaments ainsi que la nécessité de renforcer les systèmes de contrôle qualité des médicaments dans la ville de Douala

Improved stability and oral bioavailability of Ganneng dropping pills following transforming lignans of herpetospermum caudigerum into nanosuspensions / 中国天然药物

The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills (GNDP) by transforming lignans of Herpetospermum caudigerum (HL) composed of herpetrione (HPE) and herpetin (HPN) into nanosuspension (HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles (HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy (PCS), zeta potential measurement, and scanning electron microscopy (SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC, C and decrease in T when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.

Improved stability and oral bioavailability of Ganneng dropping pills following transforming lignans of herpetospermum caudigerum into nanosuspensions / 中国天然药物

The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills (GNDP) by transforming lignans of Herpetospermum caudigerum (HL) composed of herpetrione (HPE) and herpetin (HPN) into nanosuspension (HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles (HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy (PCS), zeta potential measurement, and scanning electron microscopy (SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC, C and decrease in T when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.

Estabilidad de la vacuna Candid#1 para prevenir la fiebre hemorrágica Argentina / Stability of Candid#1 vaccine to prevent Argentine Hemorrhagic Fever

Candid#1 es la primera vacuna a virus vivo atenuado producida y registrada en Argentina. Se produce en el INEVH desde 2003 para prevenir la fiebre hemorrágica argentina y se obtiene mediante cosecha de sobrenadantes de cultivos de células diploides infectadas con una cepa atenuada del virus Junín, formulación y posterior liofilización. Su estabilidad es crucial para asegurar su efectividad. El objetivo de este trabajo fue evaluar la estabilidad de Candid#1 exponiéndola a distintas condiciones de temperatura y tiempo. Tres lotes producidos en 2003 fueron sometidos al siguiente esquema de almacenamiento: (a) vacuna reconstituida conservada entre 2 °C y 8 °C durante 8 días, (b) vacuna liofilizada conservada entre 2 °C y 8 °C durante 6 meses, y (c) vacuna liofilizada conservada entre -18 °C y -20 °C durante 10 años. La potencia fue evaluada en monocapa de células Vero bajo agar. Los resultados fueron: (a) Candid#1 reconstituida fue estable 8 días entre 2 °C y 8 °C, (b) Candid#1 liofilizada fue estable 2 meses entre 2 °C y 8 °C y (c) Candid#1 liofilizada fue estable 9 años entre -18 °C y -20 °C manteniendo todos sus atributos. Estos resultados permitieron establecer las siguientes condiciones de almacenamiento: reconstituida 12 horas entre 2 °C y 8 °C, liofilizada 30 días entre 2 °C y 8 °C y 9 años entre -18 °C y -20 °C. A la luz de estos resultados, se generaron cambios favorables en las condiciones de transporte, almacenamiento y distribución de la vacuna. Se implementó la instalación de freezers domésticos en centros estratégicamente distribuidos, permitiendo preservar stocks de vacuna y distribuir las dosis necesarias a vacunatorios.

Candid#1 is the first live attenuated vaccine produced and registered in Argentina. Produced since 2003 at the INEVH to prevent Argentine hemorrhagic fever, it is obtained by harvesting supernatants of diploid cells infected with an attenuated strain of Junin virus and subsequent lyophilization. The stability of this vaccine is crucial to ensure its effectiveness. This study was aimed to evaluate the stability of Candid#1 by exposing it to different time and temperature conditions. Three vaccine batches produced in 2003 were analysed according to the following storage scheme: (a) reconstituted vaccine at 2 °C to 8°C for 8 days; (b) lyophilized vaccine at 2 °C to 8 °C for 6 months; (c) lyophilized vaccine at -18 °C to -20 °C for 10 years. The potency was assessed in Vero cell monolayers under agar. The results were: (a) reconstituted vaccine was stable between 2 °C and 8 °C for 8 days, (b) lyophilized vaccine was stable between 2 °C and 8 °C for 2 months, and (c) lyophilized vaccine was stable 9 years between -18 °C and -20 °C, keeping all its properties. These results allowed us to establish the following storage conditions and expiration times for Candid#1: (a) reconstituted: 12 hours between 2 °C and 8 °C, (b) lyophilized: 30 days between 2 °C and 8 °C and (c) lyophilized: 9 years between -18 °C and -20 °C. Based on our results, favorable changes were made in the conditions of transport, storage and distribution of the vaccine. Domestic freezers in strategically located centers were installed, allowing the preservation of vaccine stocks for distribution to secondary vaccination centers.

Preparation and characterization of alginate and gelatin microcapsules containing Lactobacillus rhamnosus

ABSTRACT This paper describes the preparation and characterization of alginate beads coated with gelatin and containing Lactobacillus rhamnosus. Capsules were obtained by extrusion method using CaCl2 as cross linker. An experimental design was performed using alginate and gelatin concentrations as the variables investigated, while the response variable was the concentration of viable cells. Beads were characterized in terms of size, morphology, scanning electron microscopy (SEM), moisture content, Fourier Transform Infrared Spectrometry (FTIR), thermal behavior and cell viability during storage. The results showed that the highest concentration of viable cells (4.2 x 109 CFU/g) was obtained for 1 % w/v of alginate and 0.1 % w/v of gelatin. Capsules were predominantly spherical with a rough surface, a narrow size distribution ranging from 1.53 to 1.90 mm and a moisture content of 97.70 ± 0.03 %. Furthermore, FTIR and thermogravimetric analysis indicated an interaction between alginate-gelatin. Cell concentration of alginate/gelatin microcapsules was 105 CFU/g after 4 months of storage at 8 oC.

Quality of bevacizumab (Avastin®) repacked in single-use glass vials for intravitreal administration / Avaliação da qualidade do bevacizumabe (Avastin®) fracionado em frascos de vidro de dose única para administração intravítrea

ABSTRACT Purpose: Avastin® (bevacizumab) is an anti-vascular endothelial growth factor (VEGF) monoclonal antibody given as an off-label drug by intravitreal administration for treatment of ocular diseases. The drug's clinical application and its cost-benefit profile has generated demand for its division into single-use vials to meet the low volume and low-cost doses necessary for intraocular administration. However, the safety of compounding the drug in single-use vials is still under discussion. In this study, the stability and efficacy of Avastin® repacked in individual single-use glass vials and glass ampoules by external compounding pharmacies were evaluated. Methods: Polyacrylamide gel electrophoresis (PAGE), size-exclusion chromatography (SEC), dynamic light scattering (DLS), and turbidimetry were selected to detect the formation of aggregates of various sizes. Changes in bevacizumab biological efficacy were investigated by using an enzyme-linked immunosorbent assay (ELISA). Results: Repacked and reference bevacizumab showed similar results when analyzed by PAGE. By SEC, a slight increase in high molecular weight aggregates and a reduction in bevacizumab monomers were observed in the products of the three compounding pharmacies relative to those in the reference bevacizumab. A comparison of repacked and reference SEC chromatograms showed that the mean monomer loss was ≤1% for all compounding pharmacies. Protein aggregates in the nanometer- and micrometer-size ranges were not detected by DLS and turbidimetry. In the efficacy assay, the biological function of repacked bevacizumab was preserved, with <3% loss of VEGF binding capacity relative to that of the reference. Conclusion: The results showed that bevacizumab remained stable after compounding in ampoules and single-use glass vials; no significant aggregation, fragmentation, or loss of biological activity was observed.

RESUMO Objetivos: Avastin® (bevacizumabe) é um anticorpo monoclonal inibidor do fator de crescimento endotelial de vasos (VEGF) utilizado "off-label" por meio de administração intravítrea para o tratamento de doenças oculares. A sua aplicação clínica associada ao custo-benefício do medicamento gerou uma demanda para seu fracionamento em frascos de dose única para utilização pela via intraocular. No entanto, a segurança do fracionamento do anticorpo em frascos de dose única ainda é alvo de discussão. Neste trabalho, a estabilidade e a eficácia do Avastin® fracionado em frascos ou ampolas de vidro de dose unitária por farmácias de manipulação do mercado foram avaliadas. Métodos: As técnicas de eletroforese em gel de poliacrilamida (PAGE), cromatografia por exclusão de tamanho (SEC), espalhamento dinâmico da luz (DLS) e turbidimetria foram empregadas para avaliar a formação de agregados de diferentes tamanhos. Alterações na atividade biológica do bevacizumabe foram estudadas utilizando ELISA. Resultados: Amostras referência e do bevacizumabe fracionado apresentaram resultados semelhantes quando analisado por gel de poliacrilamida. Por cromatografia por exclusão de tamanho, um pequeno aumento na quantidade de agregados de alta massa molar seguido de uma redução nos monômeros do bevacizumabe foram observados para as amostras das três farmácias de manipulação quando comparado ao referência. A comparação dos cromatogramas mostrou uma quantidade de redução do monômero inferior a 1% para todas as amostras fracionadas. Por espalhamento dinâmico da luz e turbidimetria, não foram detectados agregados de proteína na faixa de tamanho de micrômetro e nanômetro. No ensaio de eficácia, o bevacizumabe fracionado preservou sua função biológica pois apresentou menos de 3% de perda na capacidade de ligação ao VEGF quando comparado ao referência. Conclusão: Este estudo sugere que o bevacizumabe se mantem estável após fracionamento em ampolas e frascos de vidro de dose unitária pois não foram observadas agregação e/ou fragmentação de proteínas e perda de atividade biológica em quan tidades significativas.

validated stability indicating RP-HPLC method for estimation of Armodafinil in pharmaceutical dosage forms and characterization of its base hydrolytic product

The main objective of present study was to develop a RP-HPLC method for estimation of Armodafinil in pharmaceutical dosage forms and characterization of its base hydrolytic product. The method was developed for Armodafinil estimation and base hydrolytic products were characterized. The separation was carried out on C18 column by using mobile phase as mixture of water and methanol [45:55%v/v]. Eluents were detected at 220nm at 1ml/min. Stress studies were performed with milder conditions followed by stronger conditions so as to get sufficient degradation around 20%. A total of five degradation products were detected and separated from analyte. The linearity of the proposed method was investigated in the range of 20-120 micro g/ml for Armodafinil. The detection limit and quantification limit was found to be 0.01183 micro g/ml and 0.035 micro g/ml respectively. The precision % RSD was found to be less than 2% and the recovery was between 98-102%. Armodafinil was found to be more sensitive to the base hydrolysis and yielded its carboxylic acid as degradant. The developed method was stability indicating assay, suitable to quantify Armodafinil in presence of possible degradants. The drug was sensitive to acid, base and photolytic stress and resistant to thermal and oxidation

Validation and application of high performance liquid chromatographic method for the estimation of metoclopramide hydrochloride in plasma

The objective of this study was validation of a reverse phase HPLC method for the estimation of metoclopramide HCl in plasma already validated for determination of metoclopramide HCl in tablets dosage form. A reverse chromatographic method was used for estimation of metoclopramide HCl with the mobile phase of acetonitrile, 20mM potassium dihydrogen phosphate buffer solution [pH 3.0 adjusted with orthophosphoric acid] in the ratio of 40: 60. The column used was Waters C18 3.9x300mm micro Bondapak [RP]. The flow rate of the mobile phase was 2ml/ minute. The detector was set at the wavelength of 275nm. This method validated in plasma and was found to be linear, with correlation coefficient [R[2]], value of 0.9988, in the range of 48 ng/ml-0.25ng/ml. The method modified was accurate, precise, sensitive and showed good stability results. The % RSD of the retention time and peak area of metoclopramide HCl was 0.19% and 1.44% respectively. All the parameters such as specificity, linearity, range, accuracy, precision, system suitability, solution stability, detection and quantification limits were evaluated to validate this method and were found within the acceptance limits. The method can be effectively used for estimation of metoclopramide HCl in plasma

Stability indicating RP-HPLC method for simultaneous determination of gatifloxacin and dexamethasone in binary combination

Abstract In this study, conditions were optimized for development of a simple RP-HPLC method for simultaneous analysis of gatifloxacin and dexamethasone in different matrices like pharmaceuticals, human serum and urine. Good separation of gatifloxacin and dexamethasone from the induced degradation products was accomplished using C8 as stationary phase; 0.02 M phosphate buffer (pH 3.0) and methanol (42:58 v/v) as mobile phase. The concentration was measured with DAD at 270 nm. Linearity was observed in the range of 0.000040-0.000280 mol/L for gatifloxacin (r2≥0.999) and 0.000013-0.000091 mol/L for dexamethasone (r2≥0.999). Both the analyte peaks were completely separated from the peaks of induced degradation products as indicated by the peak purity index (≥0.9999 for both analytes). The optimized method is recommended to be used for concurrent analysis of gatifloxacin and dexamethasone in different matrices.