학술논문
Aplicació de la simulació de compressió a l’estudi del comportament i optimització de comprimits elaborats per compressió directa utilitzant el sistema expert SeDeM
Document Type
Dissertation/Thesis
Author
Source
TDX (Tesis Doctorals en Xarxa)
Subject
Language
Catalan; Valencian
Abstract
Tablets are the most common solid oral dosage forms. Direct Compression (DC) is a good methodology due to its low manufacturing times and a reduced number of steps. However, this methodology requires powders which display adequate properties in order to be compressible. The need of a swift design of pharmaceutical formulations which fulfill the compression standards and the scale-up led to create expert systems and press simulators. In this thesis, the expert system SeDeM is optimized: a new methodology to determine the Cohesion Index is stablished and two new mechanical parameters are introduced (Melting point and Ejection Force). Then, the results obtained from the SeDeM diagram are compared against the results obtained from the Styl’ONE press simulator in simulated industrial conditions. The results indicates that the new methodology is more accurate and it has been demonstrated in the development of a formula, and the comparison of different Microcrystalline Celluloses from different manufacturers. The inclusion of the two new mechanical parameters has increased the SeDeM’s reliability index. Then, three formulas developed by DC and two developed by wet granulation were compressed by means of Styl’One press simulator. Five different rotatory press’ compression profiles were simulated (Korsch XL 400, Fette 2090, Fette 3100, Kilian RX 47 I Kilian S 250) under different compression conditions. The results show the accuracy of SeDeM system and seems to indicate a correlation between Carr’s Index and Inter particle porosity Index, low radius values and capping phenomenon during the compression process. These issues where solved by applying a pre-compression force. Moreover, the DC formulas display results similar or higher than the wet granulation formulas. In conclusion, the SeDeM expert system has been optimized, correcting the Cohesion Index deviations and increasing the reliability index by adding two mechanical parameters. The Styl’One press simulator has enabled to highlight the SeDeM system’s accuracy and robustness on choosing the most optimal formulation as well as the most optimal compression conditions in order to maximize the process’ efficiency and the scale-up.