ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Objective To prepare optimization of palonosetron hydrochloride oral disintegrating tablets by orthogonal test. Methods Palonosetron hydrochloride oral disintegrating tablets were prepared with direct compression process.The content of pal-onosetron hydrochloride was determined by HPLC.The formulation was optimized with disintegration time as evaluation indices. Results The optimal formulation(60 mg/tablet)was as follows:L-HPC 12%,mannitol∶SMCC= 2∶1,magnesium stearate 2%, stevia glycosides 3%.The oral disintegrating tablets showed dine appearance and tested better;the disintegration time was 12 sec-onds;the tablets featured a hardness of 3 kg;4 min dissolution rate was 99%.Conclusion The preparation method is simple and reasonable,and the tablets can disintegrate rapidly.
ABSTRACT
Objective To investigate mechanical performances of two different drug eluting stents (DES) during compression process, so as to provide a scientific guideline for design of DES. Methods Using Solidworks, two kinds of stent models, namely the common DES without slots in outside surface (Stent I) and the targeted DES with slots in outside surface (Stent II) were established, respectively. The important mechanical properties of the two stents during compression process, such as rebound ratio of radial contraction, rebound ratio of axial contraction, the inhomogeneity of compression and the distribution of residual stress, were analyzed by ABAQUS. Results With the same outer radius, the difference values of rebound ratio of radial contraction, rebound ratio of axial contraction and inhomogeneity of compressing for the two stents were 0.07%-0.12%, 0.016%-0.033% and 0.013 %-0.048%, respectively; there was a bigger low-stress area on the support of Stent II. Conclusions Compared with the traditional DES, the targeted DES could maintain the same mechanical performances while reducing drug-loading capacity, which shows a good prospect in clinical application of the treatment for cardiovascular stenosis diseases.