Physicochemical and microbiological stability study of two new preservative-free methylprednisolone eye drops. / Estudio de estabilidad fisicoquímica y microbiológica de 2 nuevos colirios de metilprednisolona sin conservantes.

OBJECTIVE: To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 mg/ml and 10 mg/ml eye drops for use in ocular pathologies such as Sjögren's syndrome and dry eye syndrome. METHOD: The two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5 ±3 °C), at room temperature (25 ± 2 °C), and at 40 °C (±2 °C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30 days in open containers and up to 90 days in closed ones. RESULTS: The eye drops stored at 5 °C were the most stable; in the 1 mg/ml eye drops, degradation of the drug fell below 90% from day 21, and in the 10 mg/ml eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5 °C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10 mg/ml, presented a white precipitate from day 14 and 28 respectively. Non-refrigerated 1 mg/ml eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90 days in the closed containers, although microbial contamination was detected from day 21 in the open containers. CONCLUSIONS: 1 mg/ml MTPSS eye drops show physicochemical and microbiological stability for 21 days under refrigeration, compared to 42 days for 10 mg/ml eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7 days after opening.

Estabilidad del colirio de insulina para el tratamiento de úlceras corneales refractarias / Stability of insulin eye drops in the treatment of refractory corneal ulcers

Objetivo: Determinar y comparar la estabilidad físico-química y microbiológica de dos colirios de insulina 25 UI/ml elaborados con suerofisiológico o balanced salt solution bajo diferentes condiciones de conservación durante 120 días.Método: Los colirios se elaboraron por triplicado con insulina Actrapid®100 Ul/ml y balanced salt solution o suero fisiológico como vehículo, yfueron conservados a temperatura ambiente (25 °C), en nevera (2-8 °C)o congelador (–20 °C) durante 120 días. Se determinó la concentraciónde insulina mediante cromatografía liquida de ultra alta resolución, laosmolalidad y el pH a días 0, 3, 7, 15, 30, 60, 90 y 120. Asimismo, seextrajeron muestras para estudios microbiológicos en los días 0, 15, 30,60, 90 y 120.Resultados: La formulación elaborada con suero fisiológico mantuvola concentración de insulina por encima del 90% con respecto a la inicialtras 120 días de estudio en todas las condiciones de temperatura. En elcaso del colirio elaborado con balanced salt solution, la concentraciónse mantuvo estable en ambiente y congelador tras 120 días, aunque ennevera descendió por debajo del 90% a día 90 de estudio. Los valoresde osmolalidad y pH se mantuvieron constantes en ambas formulacionesy condiciones de conservación. No se observó crecimiento microbiológico en ninguna de las muestras retiradas.Conclusiones: El colirio de insulina 25 UI/ml elaborado con suerofisiológico es estable 120 días, conservado tanto a temperatura ambientecomo en nevera o congelador, protegido de la luz. Con balanced saltsolution permanece estable 120 días a temperatura ambiente y congelador, reduciéndose el periodo de validez a 90 días en el caso de laconservación en nevera. (AU)

Objective: To determine and compare the physicochemical and microbiological stability of two 25 IU/mL insulin eye drop formulations madewith normal saline and a balanced salt solution, respectively, stored for120 days under various conditions.Method: Eye drops were compounded in triplicate with 100 IU/mLActrapid® insulin and either normal saline or a balanced salt solution asvehicles, and they were stored alternatively at room temperature (25 °C),in a refrigerator (2-8 °C) or in a freezer (–20 °C) for 120 days. Insulinconcentrations were determined by ultra-high resolution liquid chromatography, and osmolality and pH values were measured at days 0, 3, 7,15, 30, 60, 90 and 120. Likewise, samples were extracted for microbiological studies on days 0, 30, 60, 90 and 120.Results: The formulation made with normal saline maintained insulinconcentrations above 90% of the baseline level after 120 days acrossall temperature conditions. In the case of the balanced salt solution-basedeye drops, insulin concentration when stored at room temperature or inthe freezer remained stable after 120 days, although insulin concentrationwhen stored in the refrigerator fell below 90% on day 90 of the study.Osmolality and pH values remained constant in both formulations andacross all storage conditions. No microbiological growth was observedin any of the samples. Conclusions: 25 IU/mL insulin eye drops made with normal salineremain stable for 120 days whether they are stored at room temperature,in a refrigerator or in a freezer, provided that they are protected fromlight. When made with a balanced salt solution, they remain stable for120 days at room temperature and in a freezer, their shelf life being reduced to 90 days in the case of storage in a refrigerator. (AU)

Presión intraocular preoperatoria en el control del cierre angular primario tratado con extracción del cristalino / Preoperative intraocular pressure for the control of primary angle closure treated with clear lens extraction

Introducción: la extracción del cristalino transparente en pacientes con cierre angular primario se plantea si existe presión intraocular mayor o igual que 30 mm Hg o daño por glaucoma. En ojos con elevación moderada de la presión intraocular se desconocen los resultados. Objetivo: evaluar la influencia de la presión intraocular preoperatoria en el control del cierre angular primario tratado con extracción del cristalino transparente. Material y Métodos: se realizó un estudio pre-experimental, entre enero de 2013 y enero de 2020, incluyó 78 ojos de 78 pacientes con cierre angular primario tratados con extracción del cristalino transparente; divididos en dos grupos según presión intraocular preoperatoria. Para el análisis estadístico se empleó chi cuadrado de independencia, probabilidad exacta de Fisher, prueba t para muestras independientes y análisis de varianza de medidas repetidas; con significación estadística del 95 por ciento. Resultados: hubo diferencias significativas entre ambos grupos para longitud axial (p=0,003), grosor del cristalino (p<0,001) y espesor corneal central (p=0,016). La presión intraocular y número de colirios, variaron de forma muy significativa (p<0,001) entre el pre y posoperatorio, y entre ambos grupos en los diferentes momentos analizados. En el grupo A el 94,4 por ciento de los ojos mostró control absoluto posoperatorio invariable en el tiempo, en el grupo B la mayoría de los ojos tuvo control relativo con diferencias muy significativas (p<0,001) entre ambos. Conclusiones: la presión intraocular preoperatoria influye en el control del cierre angular primario tratado con extracción del cristalino transparente; valores previos menores que 30 mm Hg, propician mejor control posoperatorio(AU)

Introduction: Clear lens extraction is considered in patients older than 50 years with primary angle closure and intraocular pressure greater than or equal to 30 mm Hg or damage due to glaucoma. The results are unknown in eyes with a moderate elevation of intraocular pressure. Objective: To evaluate the influence of preoperative intraocular pressure in the control of the primary angle closure treated with clear lens extraction. Material and Methods: A pre-experimental study was conducted between January 2013 and January 2020. It included a total of 78 eyes of 78 patients with primary angle closure treated with clear lens extraction. They were divided into two groups according to preoperative intraocular pressure. For statistical analysis, Chi-square test, Fisher's exact probability test, and t test were used for independent samples and analysis of variance with repeated measurements; with 95 percent statistical significance. Results: There were significant differences in axial length (p=0,003), lens thickness (p<0,001) and central corneal thickness (p=0,016) between both groups. Intraocular pressure and the number of eye drops varied very significantly (p<0,001) between the pre-and postoperative periods and between both groups at the different moments analyzed. In group A, 94,4 percent of the eyes showed absolute postoperative control, which remained unchanged over time. In group B, most eyes had relative control. There were very significant differences (p<0,001) between both groups. Conclusions: Preoperative intraocular pressure influences the control of primary angle closure treated with clear lens extraction; previous values less than 30 mm Hg favor better postoperative control(AU)