Estabilidad del plasma rico en plaquetas obtenido en sistema abierto / Stability of platelet-rich plasma obtained in an open system

Introducción: Para proteger la actividad biológica y evitar la degradación de un producto se deben mantener estrictas condiciones de obtención y almacenamiento. La información que avala el tiempo y las condiciones de almacenamiento debe partir de estudios de estabilidad realizados a largo plazo, en tiempo y condiciones de almacenamiento reales. Objetivo: Evaluar la estabilidad en vida de estante y condiciones de estrés del plasma rico en plaquetas obtenido en sistema abierto. Métodos: Se diseñó un estudio de estabilidad siguiendo las normas descritas por el Centro para el Control Estatal de los Medicamentos. Se evaluaron las principales propiedades fisicoquímicas y biológicas del plasma rico en plaquetas. Las pruebas para demostrar estabilidad del producto se realizaron con una duración de tres días y una frecuencia de ensayo en las horas 0, 4, 8, 12, 24, 48 y 72. Resultados: Los ensayos de pH mostraron que se mantiene estable con independencia del tiempo y la temperatura con un 95 % de confiabilidad. El 100 % de las muestras estudiadas no presentó variación en relación con las características organolépticas y el volumen. La esterilidad tampoco mostró variaciones. Las concentraciones del plasma rico en plaquetas según tiempo y temperaturas arrojaron una significación mayor de 0,05 con variación en función del tiempo y las temperaturas con una confiabilidad del 95 %. Conclusiones: Se demostró que el proceso de elaboración del plasma rico en plaquetas se lleva a cabo de forma controlada y segura. El plasma rico en plaquetas obtenido mantiene sus propiedades físicas, químicas y biológicas tras someterlo a diferentes tiempos y temperaturas de almacenamiento.

Introduction: To maintain biological activity and avoid degradation of a product, strict conditions of collection and storage must be maintained, the information that supports the time and storage conditions must be based on long-term stability studies carried out in real time and storage conditions. Objective: To evaluate the shelf life stability and stress conditions of the platelet rich plasm obtained in an open system. Methods: A stability study was designed following the standards described by the Center for State Control of Medicines, where the main physicochemical and biological properties of platelet rich plasm were evaluated, the tests to demonstrate product stability were carried out with a duration of three days. and a test frequency at 0, 4, 8, 12, 24, 48 and 72 hours. Results: The pH tests showed that it remains stable regardless of time and temperature with 95% reliability, 100% reliability. The samples studied did not present variation in relation to the organoleptic characteristics and volume, sterility in general did not show variations either, platelet rich plasm concentrations according to time and temperatures showed a significance greater than 0.05 with variation depending on time and temperatures with a reliability of 95%. Conclusions: The present work shows that the platelet rich plasm elaboration process is carried out in a controlled and safe way, the platelet rich plasm obtained maintains its physical, chemical and biological properties after subjecting it to different storage times and temperatures.

Accelerated stability test of sustained-release thienorphine loaded microspheres for injection / 药学学报

In order to meet the clinical needs of long-acting sustained-release thienorphine, injectable thienorphine loaded microspheres were developed, and the accelerated stability study was carried out to explore the suitable storage and transportation conditions of the microspheres. Using poly(lactic-co-glycolic acid) (PLGA) as carrier material, 3 batches of microspheres were prepared in pilot scale with emulsion solvent evaporation method. By investigating the in vitro release of thienorphine loaded microspheres at 37, 45, 52, and 60 ℃, and applying the Arrhenius equation, the linear relationship between the release rate constant (lgk) and the temperature (1/T) was established to obtain the equation: lgk = -8.073/T + 24.35 (R2 = 0.985 3), which showed that the release of microspheres at high temperature can be used to predict the release in vitro at 37 ℃, and 52.0 ± 0.5 ℃ was selected as the accelerated release condition in vitro. The quality research methods were established to investigate the changes of critical quality attributes such as microsphere morphology, drug loading, particle size and distribution, polymer molecular weight, and the related substances under accelerated conditions. The difference factor f1 and similarity factor f2 were used to assess the similarity of release behavior under accelerated conditions. The results showed that under the accelerated experimental conditions of 25 ± 2 ℃ and relative humidity (RH) 60% ± 5%, the critical quality attributes of injectable thienorphine loaded microspheres had no significant change in 6 months, suggesting that the long-term storage condition could be 5 ± 3 ℃.

Shelf life evaluation of Laghu Sutashekhara Rasa – A preliminary assessment

Background: Laghu Sutashekhara Rasa (LSR) is a herbo mineral formulation containing Shuddha Gairika(Fe2O3) and Shunthi (Zingiber officinale Roxb.) with the levigation of Nagawalli Swarasa (fresh juice ofPiper betel Linn.) prepared as per the reference of Rasatarangini Parishistha. This is an importantformulation in Ayurveda therapeutics, but its shelf life is not evaluated till date. The Govt. of India Gazettespecifies the shelf life of various Ayurvedic medicines. However, there is a need to revalidate the shelf lifeof individual formulations by following parameters prevalent in respective scenario.Objectives: To evaluate shelf life of Laghu Sutashekhara Rasa.Materials and methods: Laghu Sutashekhara Rasa was prepared in the Pharmacy, Gujarat Ayurved University, Jamnagar following classical guidelines. The samples were subjected to accelerated stabilitystudy maintaining temperature and humidity 40 ± 2 _x005F_x005F_x0001_C and 75 ± 5% respectively. Relevant analyticalparameters were analyzed at an interval of 0, 1, 3 and 6 months to check the degradation levels in theformulation.Result: Product was free from microbial contamination and heavy metals were within the prescribedlimits. There were insignificant changes in physico-chemical profiles at different intervals of analysis.On extrapolation of the observations, the shelf life of Rasayoga was found to be 2 years and 8 months.Conclusion: The shelf life of Laghu Sutashekhara Rasa was found to be less than the given standards inofficial gazettes of Govt. of India. This decreased shelf life may be because of the predominantly(approximately 70%) herbal component present in the formulation.

Properties and dissolution of curcumin-PVP co-grinding powder / 中草药

Objective: To investigate the application characteristics of excipient copovidone in co-grinding process and the feasibility of co-grinding products for improving the dissolution of curcumin, using curcumin as a model drug in vitro. Methods: The prepared products were obtained by curcumin and various proportions (0%, 1%, 3%) of copovidone in co-grinding process, which were characterized by laser particle size analyzer, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray powder diffraction (XRPD). The in vitro dissolution of milled products was evaluated in two media, and their accelerated stability was investigated. Results: In comparison with pure curcumin, the particle size of milled products decreased with the lower crystallinity by XRPD analysis, but the hygroscopicity and DSC thermograms showed no significant difference. Moreover, compared with pure curcumin, the products exhibited significant improvement of in vitro dissolution. Also, there was no significant difference in the dissolution behavior of products placed under the accelerated conditions (40 ℃, RH 75%) for three months, indicating their good stability. Conclusion: As a new excipient, copovidone could effectively enhance the dissolution of curcumin via co- grinding process. This study provided a feasible strategy for improving the solubility and even oral bioavailability of poorly soluble drugs.

Screening of Ketoprofen-Poloxamer and Ketoprofen-Eudragit solid dispersions for improved physicochemical characteristics and dissolution profile

The aim of the present study was to enhance the dissolution rate of an NSAID drug Ketoprofen by formulating it into solid dispersions with water soluble carrier Poloxamer 188 and Eudragit S 100. The solid dispersions of Ketoprofen with Poloxamer 188 were prepared at 1:1, 1:1.5 and 1:2 (Ketoprofen: Poloxamer 188) ratio by Solvent evaporation methods. The same concentration ratio was used for the preparation of solid dispersion with Eudragit S 100 by melting/fusion technique. Further, solid dispersions were investigated by solubility, ATR-FTIR, XRD, DSC, surface morphology, in-vitro dissolution and accelerated stability study. Results demonstrated that both Poloxamer 188 and Eudragit S 100 improve solubility of drugs by 8­10 folds. The result of ATR-FTIR study showed the slight shifting/broadening of principle peaks. In vitro dissolution studies showed that in the solid dispersion system containing Ketoprofen: Poloxamer 188 batch P2 (1:1.5) gives faster dissolution rate of Ketoprofen than the physical mixtures. The solid dispersion with Eudragit S 100, batch E1 (1:1) gives faster dissolution rate of Ketoprofen than the physical mixtures. In phase solubility study with Poloxamer 188 showed concentration dependent solubilization of drug but Eudragit S 100 produced opposite result. The effect of pH on solubility of Eudragit S 100 was carried out which showed solubility at pH 7.4. The dissolution profile of solid dispersion with Eudragit S 100 at pH 7.4 gives excellent result. The Accelerated stability of solid dispersions & its physical mixtures were studied at 400±2 °C/75 ± 5% RH for a period of 1 month. In these studies, Solid Dispersion batches produced an unstable formulation. The Ketoprofen solid dispersions with Poloxamer 188 and Eudragit S 100 could be introduced as a suitable form with improved solubility

Stability of multiple components in Er-Zhi-Wan (water honey pills) by UPLC-Q/TOF-MS / 中草药

Objective: According to the ICH guideline, the long-term stability and accelerated stability testing for Er-Zhi-Wan (water honey pills) has been carried out on the basis of the qualitative and quantitative analysis on multiple components in Er-Zhi-Wan by using UPLC-Q-TOF/MS method. In addition, the influence factors of the preparation (packing material and sealing process) were investigated by UPLC method. Methods: The analysis was performed on an Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with the mixture of acetonitrile-water-formic acid as mobile phase, the flow rate was 0.2 mL/min and MS scanning mode was positive and negative. According to the ICH guideline, the 18 months long-term stability [(25 ± 2) ℃, relative humidity (RH) of (60 ± 5)%], accelerated stability testing [(40 ± 2) ℃, RH of (75 ± 5)%], and influence factors of preparation (packing material and sealing process) for Er-Zhi-Wan (water honey pills) have been carried out by the UPLC method. Results: A total of 20 chemical compounds (salidroside, wedelolactone, 10-hydroxyoleoside dimethyl ester, oleoside-11 methyl ester, loganic acid, echinacoside, nuezhengslaside, oleuropein acid, verbascoside/isoverbascoside, nuezhenoside, specnuezhenide, ligustroflavone, isomer of specnuezhenide, safghanoside F, isonuezhenide, nuezhenidic acid, oleuropein, nuezhenoside-G13, oleonuezhenide, and 3-O-cis-p-coumaroyltormentic acid) were identified in the qualitative study. The content of these compounds was measured by the established quantitative and semi-quantitative research methods. In long-term stability testing, the 20 compounds were all remained stable. However, in the accelerated testing, the content of 11 chemical compounds (10-hydroxyoleoside dimethyl eser, echinacoside, nuezhengslaside, oleuropein acid, verbascoside, nuezhenide, specnuezhenide, ligustroflavone, nuezhenidic acid, nuezhenoside-G13, and oleonuezhenide) decreased obviously. Taking soda-lime glass as the packaging material, the stability of Er-Zhi-Wan (water honey pills) was improved than the commercial package under the same sealing conditions. The airtightness of the packaging materials played a significant part on the pill's stability under different sealing conditions. Conclusion: The study offers the scientific and technical support for the quality control and the clinical safety of the preparation in Chinese materia medica.

Estabilidad de la crema reformulada de nitrato de miconazol al 2 % / Stability of reformulated 2 % miconazol nitrate cream

INTRODUCCIÓN: la Empresa Productora Roberto Escudero Díaz, llevó a cabo la reformulación de la crema de nitrato de miconazol al 2 por ciento, por incumplimiento de algunas especificaciones de calidad y contaminaciones microbiológicas de varios lotes industriales, por lo que hubo que realizar cambios mayores a la composición de la formulación registrada. OBJETIVO: determinar la estabilidad de la nueva formulación de nitrato de miconazol crema al 2 por ciento, para determinar su período de validez. MÉTODOS: se realizaron los estudios según las regulaciones vigentes. Se emplearon tres lotes elaborados a escala piloto, envasados en tubos comprimibles de aluminio por 25 g. Se emplearon como métodos analíticos una técnica por cromatografía líquida de alta resolución y una por cromatografía en capa delgada previamente validadas para estos propósitos. Se consideraron dos temperaturas de almacenamiento: 30 ± 2 ºC (vida de estante) y 40 ± 2 ºC (estabilidad acelerada). Se determinaron los parámetros: propiedades organolépticas, pH, área de extensibilidad, valoración, contenido de sustancias relacionadas y/o productos de degradación, y además se evaluó la calidad de la formulación desde el punto de vista microbiológico. RESULTADOS: desde el punto de vista químico, los lotes evaluados mostraron contenidos superiores al 98 por ciento de analito y niveles muy bajos de sustancias relacionadas, independientemente del lote y la temperatura de almacenamiento. No se detectaron manchas adicionales por cromatografía en capa delgada atribuibles a posibles productos de degradación. La extensibilidad mostró un decrecimiento normal debido a la estructuración progresiva del sistema, y el pH también disminuyó discretamente pero dentro de los límites propuestos. Además se comprobó la elevada estabilidad microbiológica del medicamento a los 12 meses. CONCLUSIONES: la crema es estable química, física y microbiológicamente a temperatura ambiente durante 12 meses, por lo que se propone este tiempo como período de validez provisional(AU)

INTRODUCTION: Roberto Escudero Diaz drug producing company is carrying out the reformulation of 2 percent miconazole nitrate cream due to non-compliance with some quality specifications and the microbiological contamination of several industrial batches, so it was required to make major changes in the registered formulation composition. OBJECTIVE: to determine the stability of the new 2 percent miconazol nitrate cream formulation to verify its validity period. METHODS: the studies followed the regulations in force. Three pilot-scaled batches, packed in 25 g aluminum tubes, were used. The analytical methods were high resolution liquid chromatography technique and thin layer chromatography, being both methods previously validated for these purposes. The selected storage temperatures were 30 ± 2 °C (shelf life) and 40 ± 2 ºC (accelerated stability). The estimated parameters included organoleptic properties, pH, extensibility area, titration, content of related substances and/or degradation products in addition to evaluating the quality of formulation from the microbiological viewpoint. RESULTS: from the chemical viewpoint, the evaluated batches showed contents over 98 percent of analyte and very low levels of related substances, regardless of batch and the storage temperature. The thin layer chromatography did not detect any additional stain attributed to possible degradation products. The extensibility showed normal decrease resulting from progressive structuring of the system and the pH also lowered within the set limits. The microbiological stability of the drug was proved to be high after 12 months. CONCLUSIONS: the cream was chemically, physically and microbiologically stable at room temperature for 12 months, so this is the term suggested as the temporary validity period(AU

Stability evaluation of propolis topical bases for veterinary use

This study aimed to evaluate and select different dermatological bases incorporated with propolis for veterinary use as well as to analyze the chemical compounds of the propolis hydroalcoholic extract by LC-MS/MS. Thus, formulations were submitted to accelerated stability tests under different temperatures and to mechanical stress, and evaluated for the appearance, color, odor, pH, viscosity, spreadability, and the mean size of the dispersed globules from the internal phase during a period of three months. The creamy gel formulation showed satisfactory results for all the evaluated items with an excellent capability to incorporate the hydroalcoholic extract of propolis associated to the maintenance of its physicochemical properties. The propolis used in this study had been shown to possess antibacterial and antifungal in vitro activity against the main microorganisms responsible for such diseases. Therefore, the propolis creamy gel described here could be a promising formulation for use in the veterinary medicine.

Control de la calidad y estudio de estabilidad del paracetamol gotas orales 100 mg/ml / Quality control and stability study of 100 mg/ml paracetamol oral drops

Introducción: las gotas orales de Paracetamol, están indicadas a la población infantil hasta los 5 años para el alivio de la fiebre, dolor de cabeza, dolores dentales y proporciona alivio sintomático del resfriado común. Objetivo: validar dos métodos analíticos, para el control de la calidad y el estudio de estabilidad y estudiar la estabilidad de las gotas orales de producción nacional. Métodos: para cuantificar el principio activo para el estudio de estabilidad, la separación se realizó a través de una columna cromatográfica Lichrosorb RP - 18 (5µm) (250 x 4 mm), con detección ultravioleta a 243 nm, empleando una fase móvil compuesta por Agua destilada: Metanol (3:1). Mientras que el método para el control de la calidad se utilizó un Espectrofotómetro SPECTRONIC GENESYS 2.Para el estudio de estabilidad, se emplearon los métodos de vida de estante (a temperatura inferior a 30 º C) y de estabilidad acelerada (40 ± 2ºC) mediante cromatografía líquida de alta eficiencia. Resultados: los resultados obtenidos de los parámetros evaluados en las validaciones se encontraron dentro de los límites establecidos. Los resultados del estudio de estabilidad realizado, demuestran que el producto terminado cumplió con las especificaciones de calidad durante el estudio. Conclusiones: los métodos analíticos por espectrofotometría UV y cromatografía líquida de alta resolución, son válidos para el control de la calidad y estudio de estabilidad de las gotas orales de Paracetamol 100 mg/mL, ya que resultaron lineales, precisos, exactos y específicos. Se demostró la estabilidad física, química y microbiológica del producto por espacio de 12 meses a temperatura inferior a 30 ºC, envasados en frascos de vidrio ámbar por 15 mL, boca 18 mm, calidad hidrolítica III. Además se evidenció que el producto es estable durante 30 días después de abierto el frasco

Introduction: paracetamol is an effective analgesic and antipyretic drug of the non-steroidal anti-inflammatory drug group. Paracetamol oral drops are indicated for use in infant population aged up to 5 years to relieve fever, headache, toothache and symptomatic relief of common cold. Objective: to validate two analytical methods for the quality control and the stability study and to study the stability of 100 mg/ml Paracetamol oral drops made in Cuba. Methods: for quantification of the active principle in the final product in order to study stability, a chromatographic column equipment called Lichrosorb RP-18 was used for separation (5µm) (250 x 4 mm), with ultraviolet ray detection at 243 nm and a mobile phase made up of distilled water: methanol (3:1) and the quantification of this principle against a reference sample by using the external standard method. For the quality control, the spectrophotometry used the spectrophotometer SPECTRONIC GENESYS 2, the ideal wavelength was 245 nm since it matches the maximum absorption rate and there is no interference with the excipients. As to the stability study of the drops, the on- shelf life method (temperature below 30 C) was used, and for the accelerated stability analysis (40 ± 2ºC) through high performance liquid chromatography. Results: the results of the evaluated parameters in the validation of the methods for the quality control and the stability study were within the set limits. The results of the stability study, both accelerated and on- shelf life and reservoir use, showed that the final product met the quality specifications during the study. Conclusions: the analytical methods based on UV spectrophotometry and high performance liquid chromatography are valid for the quality control and the stability study of 100 mg/ml Paracetamol...

Design, Formulation and Evaluation of Piroxicam Capsules Prepared by Solid Dispersion Technique.

Objective: To improve the dissolution of poorly soluble Piroxicam (PRXM) by solid dispersion technique using water soluble carriers with or without the addition of sodium lauryl sulphate (SLS) as surfactant. Methods and Materials: Solid dispersions of Piroxicam were prepared using different polymers such as polyethylene glycol (PEG 4000 and PEG 6000) polyvinylpyrrolidone (PVP K30 and PVP K90) without or with addition of 2% of (SLS). Solid dispersions were formulated in drug polymer ratios 1:1, 1:2, and 1:4, each ratio without or with 2% SLS using solvent evaporation method. The prepared formulae were assayed for drug content, production yield and stability properties. Dissolution profiles were done in phosphate buffer pH 7.4 and the in vitro release was evaluated according to the % released after 20, 30, 45 and 60 minutes. An accelerated stability study was done over 3 months at 40o and 60ºC and with relative humidity (RH) 75%. Results and Discussion: All of the formulated solid dispersions displayed better dissolution profiles as compared to the pure drug. Formulae containing 2% SLS displayed better in vitro release results compared to formulae prepared without SLS. The degradation of PRXM was slow, indicating the chemical stability of PRXM in all prepared formulae. Conclusion: A formula containing PRXM to PEG 4000 in the ratio 1:1 with 2% SLS was ranked first and gave the best results among prepared formulae.

Estabilidad acelerada de un gel de Rhizophora mangle L. (mangle rojo) para heridas y quemaduras / Accelerated stability of a Rhizophora mangle L. (red mangrove) gel for wounds and burns

El objetivo del presente trabajo fue evaluar la estabilidad acelerada de un gel de Rhizophora mangle L. (mangle rojo) en dos condiciones de almacenamiento. Los 3 lotes pilotos producidos (GM01, GM02 y GM03) se almacenaron a dos temperaturas: 40 ± 2 °C durante 3 meses y 25 ± 2 °C durante 6 meses. Se realizó una evaluación de indicadores de estabilidad físico-química y microbiológica a tiempo 0, 1, 2 y 3 meses y a tiempo 0, 1, 2, 3 y 6 meses para cada una de las dos condiciones ensayadas respectivamente. Todos los lotes almacenados en ambas temperaturas mostraron estables las características organolépticas y la extensibilidad, el pH estuvo entre 6 y 7 y la reología confirmó un fluido no newtoniano del tipo Herschel Bulkley en los tiempos evaluados. La concentración mínima inhibitoria permaneció entre 8 y 10 mg/mL y la concentración de taninos entre 13 a 30 mg/g; todos los lotes se mantuvieron dentro del límite microbiano. El gel demostró tener buena estabilidad en condiciones aceleradas de temperatura, aspecto que es necesario confirmar en un próximo estudio de estabilidad en anaquel.

The objective of the present paper was to evaluate the accelerated stability of a Rhizophora mangle L. (red mangrove) gel under 2 storage conditions. The three pilot batches (GM01, GM02 and GM03) were stored at two temperature settings: 40 ± 2 °C for three months and 25 ± 2 °C for 6 months. One physical-chemical and microbiological evaluation was performed in two periods of time: at the months 0, 1, 2 and 3 for the first and at the months 0, 1, 2, 3 y 6 for the second tested storage condition. All the batches stored at both temperatures showed stable organoleptic characteristics and extensibility, the pH ranged from 6 to 7 and rheology confirmed a non-Newtonian fluid of Herschel Bulkley-type in the evaluated periods of time. The minimum inhibitory concentration remained 8 to 10 mg/mL whereas the tannin concentration ranged 13 to 30 mg/g. All the batches were within the allowable microbial limits. The red mangrove gel showed good stability under accelerated temperatures, but this is an aspect that requires to be confirmed in a future on-shelf stability study.

Estudio de estabilidad de tabletas de risperidona 3 mg / Study of stability of Risperidone (3 mg) tablets

Se desarrolló el estudio de estabilidad de las tabletas de risperidona 3 mg y se determinó su fecha de vencimiento. Este estudio se realizó por los métodos de vida de estante y de estabilidad acelerada mediante cromatografía líquida de alta eficiencia, validados en el Centro de Investigación y Desarrollo de Medicamentos. El estudio de vida de estante se desarrolló por un periodo de 24 meses a temperatura ambiente; mientras que el estudio de estabilidad acelerada se efectuó sometiendo el producto a la influencia de la luz, la humedad y la temperatura; se realizó el análisis durante 3 meses, para los 2 primeros y durante 6 meses para el estudio de la temperatura. La formulación de risperidona tabletas 3 mg cumplió con las especificaciones de calidad descritas en la Farmacopea. Los resultados del estudio de estabilidad por vida de estante después de transcurridos los 24 meses indican que el producto mantiene los parametros que determinan su calidad durante ese tiempo, y en los estudios acelerados no se observó degradación del producto. Se estableció 2 años como fecha de vencimiento en las condiciones señaladas.

Stability study was conducted of 3 mg Risperidone tablets determining its caducity date and using the shelf life methods and of accelerated stability by high-performance liquid chromatography validated in Drug Development and Research Center. The shelf life study was developed during 24 months at room temperature; whereas the accelerated stability study was performed subjecting the product to light, humidity and temperature influence. The 3 mg Risperidone tablets formula fulfilled the quality specifications described in Pharmacopeia. Results from shelf life study after 24 months show that the product maintains the parameters determining its quality during that time and in accelerated studies product degradation was noted. Under conditions signaled 2 years was established as the expiry date.

Estudio de estabilidad de tabletas de propiltiouracilo 50 mg / Study of the 50 mg Propylthiouracil tablets stability

Se desarrolló el estudio de estabilidad de las tabletas de propiltiouracilo 50 mg y se determinó su fecha de vencimiento. Este estudio se realizó por los métodos de vida de estante y de estabilidad acelerada mediante cromatografía líquida de alta eficiencia, validados en el Centro de Investigación y Desarrollo de Medicamentos. El estudio de vida de estante se desarrolló por un periodo de 24 meses a temperatura ambiente; mientras que el estudio de estabilidad acelerada se efectuó sometiendo el producto a la influencia de la luz, la humedad y la temperatura; se realizó el anàlisis durante 3 meses, para los 2 primeros y durante 6 meses para el estudio de la temperatura. La formulación de propiltiouracilo tabletas 50 mg cumplió con las especificaciones de calidad descritas en la farmacopea. Los resultados del estudio de estabilidad por vida de estante después de transcurridos los 24 meses indicaron que el producto mantenía los paràmetros que determinan su calidad durante ese tiempo, y en los estudios acelerados no se observó degradación significativa del producto. Se estableció 2 años como fecha de vencimiento en las condiciones señaladas.

Autors developed a stability study of 50 mg Propylthiouracil tablets and determination of its expiry date. This study was conducted by fixed life methods and of accelerated stability by high-performance liquid chromatography, validated in Drugs Research and Development Center. Fixed life study was conducted during 24 months at room temperature; whereas the accelerated stability study was conducted exposing the product to light influence, humidity and temperature; during 3 months a analysis was performed for the two first ones and over 6 months in the case of temperature study. Propylthiouracil formula (50 mg tablets) fulfilled the quality specifications described in Pharmacopeia. Results of stability study by fixed life after 24 monhts showed that thr product maintain the parameter determining its quality during this period, and in the accelerted studies there was not a significant degradation of product. Two years was the expity date established in above mentioned conditions.

Estudio de estabilidad acelerada del ingrediente activo D-004 en diferentes envases / Accelerated stability study of D-004 active ingredient in different containers

INTRODUCCIÓN: D-004 es un nuevo ingrediente activo en fase de investigación y desarrollo, obtenido de los frutos de Roystonea regia (Kunth) O.F. Cook. OBJETIVO: precisar la estabilidad de D-004 en condiciones aceleradas en frascos de vidrio ámbar, de tereftalato de polietileno y de polietileno de alta densidad. MÉTODOS: muestras de 3 lotes se almacenaron a (40 ± 2) ºC y (75 ± 5) porciento de humedad relativa durante 12 meses. Se determinaron las características organolépticas, la densidad relativa, el índice de refracción (USP 27) y el contenido de ácidos grasos mediante cromatografía de gases. RESULTADOS: los parámetros medidos se mantuvieron dentro de las especificaciones de calidad establecidas, con excepción del contenido de ácidos grasos, que en los frascos de tereftalato y polietileno disminuyó significativamente a los 3, 6 y 4,5 meses, respectivamente. CONCLUSIONES: el vidrio ámbar protege al D-004 de la degradación más que los envases plásticos estudiados.

INTRODUCTION: D-004 is a new active ingredient under research and development stage, which is obtained from Roystonea regia (Kunth) O. F. Cook fruits. OBJECTIVE: to precise over the D-004 stability under accelerated conditions in amber glass, polyethylene terephtalate and high density polyethylene containers. METHODS: samples from three batches were stored at (40 ± 2) ºC and (75 ± 5) percent relative humidity for 12 months. Organoleptic characteristics, relative density, refractive index (USP 27) and fatty acids content by gas chromatography, were determined. RESULTS: measured parameters were within the set quality specifications , except for fatty acids content that significantly decreased in polyethylene terephtalate and high density polyethylene containers after 3, 4 and a half and 6 months, respectively. CONCLUSIONS: the amber glass protects more D-004 from degradation than the analyzed plastic containers.

Emulsões O/A contendo Cetoconazol 2,0%: avaliação da estabilidade acelerada e estudos de liberação in vitro / O/W Emulsion Containing 2.0% Ketoconazole: Accelerated Stability Test and in vitro Release

Os objetivos do estudo foram desenvolver e avaliar a estabilidade físico-química de emulsões O/A contendo cetoconazol a 2,0% e determinar seu perfil de liberação in vitro. As formulações foram preparadas com bases auto-emulsionáveis com diferentes características químicas. A estabilidade do sistema foi avaliada de acordo com o Guia para Realização de Testes de Estabilidade em Produtos Farmacêuticos, utilizando diferentes temperaturas (4ºC, 37ºC e 45ºC) por um período de tempo de três meses. Os parâmetros avaliados durante o ensaio foram: as características organolépticas,o pH, o comportamento reológico e a concentração do ativo. A emulsão considerada estável foi submetida ao ensaio de liberação in vitro utilizando célula de difusão de Franz. A quantificação do cetoconazol na formulação e na solução receptora foi realizada por método espectrofotométrico no ultravioleta a 244 nm. Dentre as formulações testadas, somente aquela preparada com álcool cetoestearílico e estearato de polietilenoglicol (PEG20) manteve suas características físico-químicas estáveis durante o teste. O estudo de liberação in vitro demonstrou que o fármaco foi liberado do sistema gradualmente no decorrer do tempo, apresentando uma cinética pseudo zero ordem.

The goal of this work was to develop and assess the physicochemical stability of O/W emulsions containing 2.0% ketoconazole and to determine their in vitro release profile. These formulations were prepared with self-emulsifying bases that differed in their chemical characteristics. The stability of the system was assessed, as recommended in the Guide to Drug Product Stability Tests, over 3 months at 3 different temperatures (4ºC, 37ºC and 45ºC). The characteristics assessed during the test were the organoleptic properties, pH, rheological behavior and drug concentration. The most stable emulsion was subjected to an in vitro release test in a Franz diffusion cell system. The ketoconazole in both the formulation and receptor phase was determined by UV spectrophotometry at 244 nm. The O/W emulsion prepared with cetearyl alcohol and polyethylene glycol (PEG20) stearate was the only one that maintained its physicochemical characteristics throughout the test. The in vitro release test demonstrated that the drug was released gradually, exhibiting pseudo zero-order kinetics.

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.

Estabilidade e estudo de penetração cutânea in vitro da rutina veiculada em uma emulsão cosmética através de um modelo de biomembrana alternativo / Stability and in vitro penetration study of rutin incorporated in a cosmetic emulsion through an alternative model biomembrane

A rutina é empregada como antioxidante e na prevenção da fragilidade capilar. Estudos de penetração in vitro através da pele humana seria a situação ideal, entretanto, há dificuldades de sua obtenção e manutenção de sua viabilidade. Entre os demais modelos de membrana, a muda de pele de cobra se apresenta como estrato córneo puro, fornecendo barreira similar ao humano e é obtida sem a morte do animal. Os objetivos desta pesquisa foram desenvolver e avaliar a estabilidade de uma emulsão cosmética contendo rutina e, como promotor de penetração cutânea, o propilenoglicol; e avaliar a penetração e a retenção cutânea in vitro da referida substância ativa da formulação, empregando um modelo de biomembrana alternativo. A emulsão foi desenvolvida com rutina e propilenoglicol, ambos a 5,0 por cento p/p. Quantificou-se a rutina das emulsões por espectrofotometria a 361,0 nm, método previamente validado. A penetração e retenção cutânea in vitro foram realizadas em células de difusão vertical com muda de pele de cobra de Crotalus durissus, como modelo de biomembrana alternativo, e água destilada e álcool etílico absoluto 99,5 por cento (1:1), como fluido receptor. O experimento foi conduzido em um período de seis horas, a 37,0 ± 0,5 ºC e agitação constante de 300 rpm. Empregou-se o método espectrofotométrico validado a 410,0 nm para a quantificação da rutina após penetração e retenção cutânea. A emulsão não promoveu a penetração cutânea da rutina através da muda de pele de C. durissus, retendo 0,931 ± 0,0391 mg de rutina/mg de muda de pele de cobra. Nas condições de armazenamento a 25,0 ± 2,0 ºC; 5,0 ± 0,5 ºC e 45,0 ± 0,5 ºC, a emulsão apresentou-se quimicamente estável durante 30 dias. De acordo com os resultados, a emulsão não favoreceu a penetração cutânea da rutina, mas apenas sua retenção no estrato córneo de C. durissus, condição considerada estável no período de 30 dias.

Rutin is employed as antioxidant and to prevent the capillary fragility and, when incorporated in cosmetic emulsions, it must target the action site. In vitro cutaneous penetration studies through human skin is the ideal situation, however, there are difficulties to obtain and to maintain this tissue viability. Among the membrane models, shed snake skin presents itself as pure stratum corneum, providing barrier function similar to human and it is obtained without the animal sacrifice. The objectives of this research were the development and stability evaluation of a cosmetic emulsion containing rutin and propylene glycol (penetration enhancer) and the evaluation of rutin in vitro cutaneous penetration and retention from the emulsion, employing an alternative model biomembrane. Emulsion was developed with rutin and propylene glycol, both at 5.0 percent w/w. Active substance presented on the formulation was quantified by a validated spectrophotometric method at 361.0 nm. Rutin cutaneous penetration and retention was performed in vertical diffusion cells with shed snake skin of Crotalus durissus, as alternative model biomembrane, and distilled water and ethanol 99.5 percent (1:1), as receptor fluid. The experiment was conducted for six hours, at 37.0 ± 0.5 ºC with constant stirring of 300 rpm. Spectrophotometry at 410.0 nm, previously validated, determined the active substance after cutaneous penetration/retention. Emulsion did not promote rutin cutaneous penetration through C. durissus skin, retaining 0.931 ± 0.0391 mg rutin/mg shed snake skin. The referred formulation was chemically stable for 30 days after stored at 25.0 ± 2.0 ºC, 5.0 ± 0.5 ºC and 45.0 ± 0.5 ºC. In conclusion, it has not been verified the active cutaneous penetration through the model biomembrane, but only its retention on the Crotalus durissus stratum corneum, condition considered stable for 30 days.

Accelerated chemical stability data of O/W fluid emulsions containing the extract of Trichilia catigua Adr. Juss (and) Ptychopetalum olacoides Bentham

Development of topical dosage forms requires physical, physicochemical and chemical assays that provide, as soon as possible, the formulation with the best stability profiles. This study evaluated the stability of O/W fluid emulsions, by total flavonoids determination, expressed in rutin, containing the standardized extract of Trichilia catigua Adr. Juss (and) Ptychopetalum olacoides Bentham. Samples were evaluated for 90 days stored at 24.0 ± 2.0 ºC, 5.0 ± 0.5 ºC and 40.0 ± 0.5 ºC, following a protocol for the assessment of accelerated chemical stability assay, also known as Normal Stability Test. A sensitive UV-spectrophotometric method at 361.0 nm was previously validated for the determination of the active substance. By Normal Stability Test, the O/W fluid emulsions presented acceptable chemical stability, for at least 90 days, when the samples were stored at 24.0 ± 2.0 ºC and 5.0 ± 0.5 ºC. The storage condition at 40.0 ± 0.5 ºC has accelerated the degradation process of the total flavonoids, consequently, those O/W emulsions containing this kind of natural active substance or a similar preparation must not be stored at elevated temperatures.

O desenvolvimento de formas farmacêuticas tópicas necessita ensaios físicos, físico-químicos e químicos que selecionem rapidamente a formulação de melhor desempenho de estabilidade. Este estudo avaliou a estabilidade de emulsões O/A fluidas, por meio da determinação de flavonóides totais, expressos em rutina, contendo o extrato padronizado de Trichilia catigua Adr. Juss (e) Ptychopetalum olacoides Bentham. As amostras foram armazenadas a 24,0 ± 2,0 ºC; 5,0 ± 0,5 ºC e 40,0 ± 0,5 ºC durante 90 dias e foram avaliadas segundo o protocolo para a determinação da estabilidade acelerada, conhecida como Teste de Estabilidade Normal. A quantificação da substância ativa foi determinada por espectrofotometria na região do ultravioleta a 361,0 nm, previamente validado. Após os ensaios de estabilidade, as emulsões O/A fluidas apresentaram estabilidade adequada, pelo menos, no período de 90 dias, quando armazenadas a 24,0 ± 2,0 ºC e 5,0 ± 0,5 ºC. A condição de armazenamento a 40,0 ± 0,5 ºC acelerou a cinética de degradação dos flavonóides totais, expressos em rutina, portanto, preparações possuindo esta categoria de substância ativa natural ou formulações similares não devem ser armazenadas em temperaturas elevadas.

Apply the accelerated stability test to predict the self-life of national standard serum tetanus antitoxin

Accelerated stability test has been applied for predicting self-life of national standard serum tetanus anti-toxin (SAT). Samples of the tetanus antitoxin were kept at - 20°C, 4°C, 22°C, 37°C and 45°C for 6 months and their potency was estimated by using the toxin neutralization method on mice. There was relationship between the potency change and the self- life of serum tetanus antitoxin by using Arrhenius equation. The results demonstrated that the self-life of the national standard serum tetanus antitoxin was 9 years and 6 months when stored at -20°C.