Comparing failure tests on pharmaceutical tablets: Interpretation using experimental results and a numerical approach with cohesive zone models

The mechanical strength is an important quality attribute of pharmaceutical tablets. It can be determined using different failure tests like the Brazilian test or the three-point bending test. Nevertheless, literature shows that different failure tests often give conflicting values of tensile strengths (TS), which are generally calculated using the maximum stress criterion as a failure criterion. This work started from the hypothesis that these discrepancies are in fact due to the application of this criterion which is not suited to study pharmaceutical tablets, first due to heterogeneity of the stress distributions during the tests and second due to the quasi-brittle nature of pharmaceutical tablets. As an alternative, a numerical fracture criterion which is known to be well-suited for quasi-brittle solids (cohesive zone model, CZM) was used and calibrated using experiments. Using this approach, the breaking forces obtained numerically were shown to be in fair agreement with the experimental ones. Above all, the numerical results made it possible to catch the trends when comparing the different failure tests one to another. Especially, the model made it possible to retrieve the factor 2 between the TS obtained by three-point bending and by diametral compression found in the literature

Fate of Tableted Freeze-Dried siRNA Lipoplexes in Gastrointestinal Environment

The incorporation of siRNA into nanocarriers is mandatory to facilitate its intracellular delivery, as siRNA itself cannot enter cells. However, the incorporation of these nanocarriers into oral, solid dosage forms and their fate in the gastrointestinal environment is yet to be explored. In the present work, the fate of, (i) naked siRNA, (ii) freshly prepared siRNA lipoplexes, and (iii) tableted siRNA lipoplexes, in simulated gastric and intestinal fluids was studied. The siRNA, either released from or protected within the lipoplexes, was quantified by gel electrophoresis and siRNA efficacy was assessed in cell transfection. The freshly prepared lipoplexes kept their siRNA load and transfection efficiency totally preserved during 1 h of incubation in simulated gastric fluid at 37 °C. However, in simulated intestinal fluid, despite no release of siRNA from lipoplexes after 6 h of incubation, gene silencing efficacy was dramatically decreased even after 1 h of exposure. The lipoplexes obtained from tablets efficiently protected siRNA in simulated gastric fluid, thus preserving the gene silencing efficacy, whereas their incubation in simulated intestinal fluid resulted in a marked siRNA release and decreased gene silencing efficacy. These results provided a detailed explanation for understanding the fate of siRNA in gastrointestinal conditions, when simply loaded in lipoplexes or formulated in the form of tablets

Du contrôle qualité à l'amélioration continue (exemple du processus de gestion des déviations)

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Relation client/fournisseur (de l'agrément des fournisseurs à leurs qualification en vue de leur sous-traiter les controles à réception)

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Dispositifs Qualité d'un service de pharmacovigilance

La pharmacovigilance est une discipline évolutive qui a connu d importantes modifications comme récemment la transposition des directives européennes en droit national applicable depuis le 2 juillet 2012. De ce fait, il est nécessaire de déployer des dispositifs qualités pour assurer les obligations de pharmacovigilance d un service de façon permanente et continue afin de renforcer la performance du processus par une approche d amélioration continue de la qualité du système de pharmacovigilance. Ce document illustre les différents dispositifs qualités d un service de pharmacovigilance au sein d une entreprise pharmaceutique. Ces dispositifs en lignes avec la nouvelle réglementation renforcent la gestion qualité du système de pharmacovigilance. Ils permettent de pérenniser l esprit d amélioration continue dans la surveillance de la sécurité d un médicament. Enfin, ce document présente des exemples d outils de surveillance qui permettent d évaluer les processus mis en place afin de garantir leur bon fonctionnement conformément aux exigences réglementaires.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Mise au point d'une méthode de dosage de la N-acétylcystéine (validation analytique et application clinique)

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Etude des lois de mélange en compression et caractérisation par microscopie infrarouge

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Validation de la méthode d analyse du carbone organique total et des méthodes de prélèvement dans le cadre de la validation des procédés de nettoyage

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

La rénovation des installations de traitement d'eau purifiée au sein d'unités de production pharmaceutique

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Implémentation d un outil de gestion électronique des documents sur un site de distribution

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF