Efecto de la fuerza de compresión sobre los atributos críticos de calidad en tabletas de liberación inmediata de furosemida / Effect of compression force on critical quality attributes of immediate release tablets of furosemide

RESUMEN La furosemida es un fármaco poco soluble en agua (0,01825 mg/mL). Debido a su baja solubilidad y baja permeabilidad, se ubica en la clase IV del Sistema de Clasificación Biofarmacéutica (BCS, por sus siglas en inglés). Se absorbe rápida pero incompletamente en el tracto gastrointestinal (GI). Actualmente, este fármaco se comercializa en tabletas, las que para su obtención deben ser sometidas a un proceso de compresión. La fuerza aplicada en dicha compresión puede influenciar algunas de las características de calidad del producto; por ello, la presente investigación estudia el efecto de la fuerza de compresión sobre los atributos críticos de calidad en el proceso de fabricación (dureza, friabilidad y desintegración) y en el producto terminado (uniformidad de dosificación y disolución) de comprimidos de furosemida. El efecto sobre la disolución se determinó por los factores de diferencia (f 1) y de similitud (f 2) de los perfiles de disolución y los parámetros de eficiencia de la disolución (ED) y tiempo medio de disolución (TMD), los cuales se calcularon con el software académico kinetDS®. Los resultados obtenidos permitieron definir el rango de la fuerza de compresión para el cual se obtuvo una ED superior al 85% y un TMD inferior a 7,5 min.

SUMMARY Furosemide is poorly water soluble drug (0.01825 mg/mL). Due to its low solubility and low permeability, it is labeled in class IV of the Biopharmaceutical Classification System (BCS). It is rapidly but incompletely absorbed from the gastrointestinal (GI) tract. Currently, this drug is marketed as tablets, which should be subjected to a compression process. The force applied in this compression can influence some of the quality characteristics of the product. Therefore, this investigation was carried out to determine the effect of compression force on the critical quality attributes of the product in process (hardness, friability and disintegration) and of the finished product (uniformity of dosage and dissolution). The effect on the dissolution was determined by the difference factor (f 1) and similarity factor f 2 ) of the dissolution profiles, the dissolution efficiency (ED) and mean dissolution time (TMD) parameters, which were calculated by kinetDS® academic software. The results obtained allowed to define the range of compression force for which the ED was higher than 85% and the TMD lower than 7.5 min.

Formulation and Design of Multiunit Particulate System (MUPS) Tablet of Pantoprazole by QbD: Effect of Compression Variables on the Finished Product.

The aim of the study was to optimize compression process variables of Pantoprazole oro-dispersible (Multiunit particulate system) MUPS tablet. Enteric coated Pantoprazole pellets were compressed to oro-dispersible tablet for geriatric and pediatric patients for easy administration. The risk related to compression process variables was identify, assessed and mitigated using Failure Mode and Effect Analysis (FMEA). A full factorial design was applied to develop design space and determine control strategy for compression process, which were developed, have promising chemical and physical results. The compression process variables studied were pre-compression force (X1), main compression force (X2) and turret speed (X3), versus affecting hardness (Y1), disintegration time (Y2), friability (Y3), weight variation (Y4), content uniformity (Y5), drug release in 0.1N HCl (Y6) and assay (Y7) as responses/Critical quality attributes (CQAs). Response surface graphs depicted that X2 had more impact on CQAs than X1. Design space plot revealed that tablet CQAs were within limit when X3 maximum 44 rpm and X2 in the range of 10 to 12.5 kN. Scale up performed on commercial scale compression machine of same make that of lab scale showed reproducible physical and chemical parameters. It could be concluded that a quality Pantoprazole oro-dispersible MUPS tablet was successfully designed using QbD approach to compression process variables.

Avaliação dos diferentes métodos de medida de força de compressão em três equipamentos mamográficos diferentes / Evaluation of diverse methods for measuring compression force in three different mammographic systems

OBJETIVO: Verificar a concordância dos resultados apresentados por diferentes métodos de medida e as variações apresentadas na aplicação deles em diferentes equipamentos mamográficos. MATERIAIS E MÉTODOS: Foram realizadas 10 medidas de força de compressão para cada método proposto em cada equipamento avaliado (Mammomat 3000-Siemens, Mammo Diagnostic UC-Philips e Alpha ST-GE), sendo avaliadas as diferenças entre esses equipamentos mamográficos para aplicação dos mesmos métodos de medida e as diferenças entre os métodos aplicados. RESULTADOS: Diferenças significativas foram observadas entre os resultados para os diferentes métodos propostos, sendo o valor medido com auxílio de "balança tipo de banheiro", o que subestimou o valor da força de compressão. Cada sistema de compressão mostrou diferentes respostas para os métodos propostos. CONCLUSÃO: Diferenças foram verificadas para os sistemas de compressão e métodos utilizados. Dessa forma, a escolha do modo de realização do teste de compressão torna-se importante para aceitação de equipamentos mamográficos, e a competência para a definição do método mais adequado e realista é do responsável técnico. Sugere-se que a medida de força de compressão seja realizada com auxílio de dinamômetro de extensão e não de compressão se não se conhece o funcionamento do sistema de compressão do mamógrafo.

OBJECTIVE: To evaluate the intermethod agreement in the measurement of compression force as well as variations in the testing of different mammography systems. MATERIALS AND METHODS: Ten compression force measurements were performed for each proposed method on each mammography apparatus (Mammomat 3000-Siemens, Mammo Diagnostic UC-Philips and Alpha ST-GE), with an evaluation of the differences among the mammographic equipments as far as the application of such measurement methods is concerned, as well as the differences among the applied methods. RESULTS: Significant differences were observed among the results for the different systems and methods, and the values measured with the aid of a bathroom-scale-type dynamometer resulted in compression force underestimation. Each compression system presented different responses for the proposed methods. CONCLUSION: Differences were observed among compression systems and among proposed methods. Thus the choice of the way the compression test is performed is critical for the acceptance of the mammography equipment, the technical lead being the most competent to define the most appropriate and realistic testing method. It is suggested that the compression force measurement should be performed with an extension dynamometer, rather than with a compression dynamometer, in cases where the mammography compression system functioning is not known.

The reaction of bone regenerate to the various force ratio and periods on distraction osteogenesis with combined distraction force and compression force

Experipental study of role of compression forces on distraction osteogenesis on the rat mandible

Distraction osteogenesis is a biologic process of new bone formation between the surfaces of bone segments that are gradually separated by incremental traction. Distraction osteogenesis is clinically applied as a new treatment modality of mandibular hypoplasia or bony defect area in maxillofacial area by many studies of distraction devices and method. But disadvantage of distraction osteogenesis shows unfavorably long consolidation period and relapse tendency. Therefore. this experiment was designed to investigate the effectiveness of combined application of distraction and compression force for improving of bone quality and shortening of treatment period during distraction osteogenesis. Twenty-one Sprague-Dawley rats with 300-350gm were used. These were divided into two group as distraction group and combination group was applied with compression force in the consolidation period. The rat were sacrificed for gross finding, radiographic and histologic findings. at 2, 4 weeks after distraction. The result were follow : 1. On radiographic finding, all experimental groups appeared more radiopacity than control groups both at 2, 4 weeks after distraction. 2. On histologic finding, trabeculae of bone and mature lamellar bone were showed increasingly in experimental group. Ossification occured rapidly. From this study, we may suggest that compression force application in consolidation period during distraction osteogenesis can be useful method improve bone quality and to shorten the treatment period. But more experimental and clinical studis are necessitated on effects of compression force application during distraction osteogenesis.