Quantification of Amlodipine Maleate Content in Amorphous Solid Dispersions Produced by Fluidized Bed Granulation Using Process Analytical Technology Tools.

Active pharmaceutical ingredient (API) content is a critical quality attribute (CQA) of amorphous solid dispersions (ASDs) prepared by spraying a solution of APIs and polymers onto the excipients in fluid bed granulator. This study presents four methods for quantifying API content during ASD preparation. Raman and three near-infrared (NIR) process analysers were utilized to develop methods for API quantification.

Identification of Amino Acid Residues Critical for the Interaction of Fibrin with N-Cadherin.

We recently identified N-cadherin as a novel receptor for fibrin and localized complementary binding sites within the fibrin βN-domains and the third and fifth extracellular domains (EC3 and EC5) of N-cadherin. We also hypothesized that the His16 and Arg17 residues of the βN-domains and the (Asp/Glu)-X-(Asp/Glu) motifs present in the EC3 and EC5 domains may play roles in the interaction between fibrin and N-cadherin. The primary objectives of this study were to test these hypotheses and to further clarify the structural basis for this interaction.

Identification of Neural (N)-Cadherin as a Novel Endothelial Cell Receptor for Fibrin and Localization of the Complementary Binding Sites.

Based on the high structural homology between vascular endothelial (VE)-cadherin and neural (N)-cadherin, we hypothesized that fibrin, which is known to interact with VE-cadherin and promote angiogenesis through this interaction, may also interact with N-cadherin. To test this hypothesis, we prepared fibrin and its plasmin-produced and recombinant fragments covering practically all parts of the fibrin molecule. We also prepared the soluble extracellular portion of N-cadherin (sN-cadherin), which includes all five extracellular N-cadherin domains, and studied its interaction with fibrinogen, fibrin, and the aforementioned fibrin fragments using two independent methods, ELISA and SPR.

Current View on the Molecular Mechanisms Underlying Fibrin(ogen)-Dependent Inflammation.

Numerous studies have revealed the involvement of fibrinogen in the inflammatory response. To explain the molecular mechanisms underlying fibrinogen-dependent inflammation, two bridging mechanisms have been proposed in which fibrin(ogen) bridges leukocytes to endothelial cells. The first mechanism suggests that bridging occurs via the interaction of fibrinogen with the leukocyte receptor Mac-1 and the endothelial receptor ICAM-1 (intercellular adhesion molecule-1), which promotes leukocyte transmigration and enhances inflammation.

Dual functions of the fibrin βN-domains in the VLDL receptor-dependent pathway of transendothelial migration of leukocytes.

Our previous studies revealed that fibrin interacts with the VLDL receptor (VLDLR) through a pair of its βN-domains and this interaction promotes transendothelial migration of leukocytes and, thereby, inflammation. In agreement, the NDSK-II fragment representing the central part of the fibrin molecule and containing these domains stimulates leukocyte transmigration. However, the recombinant (β15-66) fragment corresponding to a pair of the βN-domains inhibits NDSK-II-stimulated leukocyte transmigration.