A preformulation strategy for the selection of controlled-release components to simulate a subcutaneous implant / Una estrategia de preformulación para la selección de componentes de liberación controlada para simular un implante subcutáneo

Many chronic diseases require repetitive injections as maintenance treatment. It is therefore important to investigate a possible alternative. A simulated subcutaneous implant prototype was fabricated as a polymer matrix covered by cylinder-shape tubing having a porous membrane. Sucrose, bovine serum albumin, and gelatin were selected as matrix excipients. Eight APIs with different physiochemical properties were used to investigate the releasing mechanism. Drug release was tested through an in vitrodissolution apparatus. Drug release of eight APIs followed zero-order kinetics with a minimum 12-hour duration. Release rates also showed linear correlations with the APIs' solubilities under physiological pH. For releasing mechanism studies, different combinations of matrix and membrane were investigated in detail. A 144-hour continuous zero-order release of caffeine was achieved as the best controlled simulated prototype. The results showed that drug release of our simulated prototype was primarily achieved by drug diffusion rather than dissolution.

Muchas enfermedades crónicas requieren inyecciones repetitivas como tratamiento de mantenimiento. Por lo tanto, es importante investigar una posible alternativa. Se fabricó un prototipo de implante subcutáneo simulado a partir de una matriz de polímero cubierta por un tubo en forma de cilindro que tiene una membrana porosa. La sacarosa, la albúmina de suero bovino y la gelatina se seleccionaron como excipientes matriciales. Se utilizaron ocho APIs con diferentes propiedades fisicoquímicas para investigar el mecanismo de liberación. La liberación del fármaco se probó a través de un aparato de disolución in vitro. La liberación del fármaco de las ocho APIs siguió una cinética de orden cero con una duración mínima de 12 horas. Las tasas de liberación también mostraron correlaciones lineales con las solubilidades de las APIs a pH fisiológico. Para los estudios de mecanismos de liberación, se investigaron en detalle diferentes combinaciones de matriz y membrana. El prototipo simulado con mejor control logró una liberación continua de cafeína de orden cero durante 144 horas. Los resultados mostraron que la liberación del fármaco del prototipo simulado ocurrió principalmente mediante la difusión del fármaco en lugar de la disolución.

Preparation and Properties of Rapamycin Sustained-release Film / 中山大学学报(医学科学版)

@#【Objective】To prepare rapamycin（RAPA）sustained-release film and to evaluate its dissolution.【Methods】RAPA sustained- release film was created by using polymer polyactioglyconic acid （PLGA），copolymer of polyactic acid（PLA）and polyglycolic acid（PGA）. Drug content of the sustained-release film was determined using specificity test，recovery，relative standard deviation（RSD）and stability test. Then，the dissolution of the sustained- release film was analyzed.【Results】The concentration of RAPA had a linear relationship with peak area，which ranged between 0.408 μg/mL and 40.8 μg/mL through the standard curve. The specificity test of the drug content determination indicated the excipient of the film and the solution with 0.3% sodium dodecyl sulfate（SDS）did not affect in determining the RAPA content. The recovery and RSD were excellent through drug content determination in blank films，which had three different levels of RAPA concentrations. The mean RAPA content of the sustained-release films was（112.6±10.1）μg（RSD 8.99%）through the drug content determination of the films，and the stability of RAPA with 0.3% SDS was good within 15 days. In addition，dissolution test of the sustained- release film indicated that the amount of drug release reached a high level and sustained up to 15 days.【Conclusion】 The RAPA sustained-release film with certain behavioral characteristic parameters had a stable drug content and favorable sustained-release property，and it may have certain application potential in anti-proliferation after glaucoma filtering surgery.

Similarity Evaluation of the Dissolution Curves between Generic and Original Metoprolol Tartrate Tablets / 中国药房

OBJECTIVE:To establish the method for dissolution determination of Metoprolol tartrate tablets,and to evaluate the similarity of dissolution curves of generics and original drugs. METHODS:The paddle method was adopted with rotational the speed of 50 r/min,using pH 1.2 hydrochloric acid solution,pH 4.5 acetate buffer solution and pH 6.8 phosphate buffer solution as dissolution media. Fiber-optical drug dissolution real-time measurement instrument was used to determine the dissolution curves of generic and original Metoprolol tartrate tablets with optical distance of 10 mm. Similarity factor (f2) method was used to evaluate its similarity. RESULTS:In 3 dissolution mediums,the f2 of generic and original Metoprolon tartrate tablets were 80.5,66.8, 69.4,respectively,which indicated that the dissolution curves showed similarity. CONCLUSIONS:Established real-time dissolution process analysis method is suitabe for the dissolution determination of Metoprolol tartrate tablets. Generic and eriginal show the sim-ilarity in dissolation behavier,so they have good consistency in quality.

Evaluation of similarity of mean drug dissolution curves by the experimental model of reformatory Weibull / 中国药学杂志

OBJECTIVE: To evaluate the similarity of the mean drug dissolution or release curves by the experimental model of reformatory Weibull. METHODS: Three drugs were taken as the model drugs. With the fiber-optic in site dissolution testing equipment(FODT), the percentages of accumulated dissolution/release changing with time of the control and test preparations of every drug were respectively monitored. The mean percentages were calculated and the dissolution/release curves were drawn. The data were fitted by the reformatory Weibull model. The fitted parameters c, Ti, b, a, and the 95% confidence intervals of every parameters were extracted. The similarity of the mean drug dissolution curves between the control and test preparations was evaluated by the fitted parameters and observation of the dissolution curves. RESULTS: For the sustained-release preparations, there was no significant difference in the parameters c, Ti, b, and a of the test and control samples, and the mean drug release curves were similar. As for the non-modified preparations, whether the dosage forms of the test and control preparations were the same or not, there existed differences in the parameters fitted by the method of reformatory Weibull model. CONCLUSION: The modified method of reformatory Weibull model can be applied in the evaluation of similarity of drug dissolution behavior with satisfactory goodness-of-fit and quantitative result.

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