Anti-Factor VIII monoclonal antibody, clone BNWIV-9036

Cefuroxime Axetil (CA) is a poorly soluble, broad spectrum antibiotic which undergoes enzymatic degradation in gastrointestinal tract. The objective of the present study was to develop lipid-based gastro-retentive floating drug delivery systems containing CA using hot-melt extrusion (HME) to improve absorption. Selected formulations of CA and lipids were extruded using a twin screw hot-melt extruder. Milled extrudates were characterized for dissolution, floating strength, and micromeritic properties. Solid-state characterization was performed using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and hot-stage microscopy. In vitro characterization demonstrated that the formulations exhibited a sustained drug release profile for 12 h. All formulations showed desired floating and flow properties. Solid-state characterization revealed no phase separation and no chemical interactions between the drug and excipients. Based on in vitro study results, an optimized formulation (F8) was further evaluated for in vivo performance. Oral bioavailability (C(ma)(x )and AUC(0)(-)(24h)) of F8 was significantly higher than that of pure CA. This study describes the use of lipid-based gastro-retentive floating drug delivery systems to achieve desired sustained release profile for more complete dissolution which could potentially reduce enzymatic degradation. This study also highlights the effectiveness of HME technology to improve dissolution and bioavailability.

Over the past few decades, important knowledge on why inhibitors develop and better information about significant risk factors have become available. A series of both genetic and nongenetic factors are recognized and clinical score systems were proposed to quantify the risk for each patient. In addition, modulation of the immunological response was acknowledged to play a pivotal role in the occurrence of inhibitors. However, with the exception of mutation testing in severe hemophilia B patients, no single risk factor or clinical score is currently utilized in clinical practice. Omics technologies are large-scale hypothesis-generating approaches, which provide the tools to study issues contributing to a complex and multifactorial phenomenon, such as inhibitor development. Newer cutting edge technologies may enable a more accurate estimation of the personal risk profile and provide a reliable tool to accurately measure the risk periodically, thereby enabling strategies to foresee and prevent inhibitor formation.