Science- and Risk-Based Stability Strategies to Support Product Lifecycle Changes.

ICH Q12 asserts that science- and risk-based approaches are applicable to stability studies supporting Chemistry, Manufacturing and Controls (CMC) post-approval changes (PAC) to enable more timely implementation; however, no guidance or specific examples are provided to demonstrate how prior knowledge of the product can inform the risk assessment for the proposed change(s). Ten diverse case studies are presented in this manuscript to demonstrate how science- and risk-based stability strategies were used to support drug substance and product CMC PAC and lifecycle management activities. The accumulated stability knowledge held by original manufacturers of marketed products is substantial, and different elements of this knowledge base were used to assess the risks and impact of the proposed changes for confident change management.

Impact of Physicochemical Properties of Cellulosic Polymers on Supersaturation Maintenance in Aqueous Drug Solutions.

The precipitation inhibitory effect of cellulosic polymers in relation to their physicochemical properties was studied. Using a poorly water-soluble model drug, griseofulvin, the precipitation inhibitory effect of a series of hydroxypropyl methylcellulose (HPMC) and methylcellulose polymers was studied using solvent-shift method. The extent of supersaturation maintenance of each polymer was then quantified by the parameter, supersaturation factor (SF).

Factor VII activating protease (FSAP) influences vascular remodeling in the mouse hind limb ischemia model.

Background: Investigations in factor VII activating protease (FSAP) mice suggest a role for FSAP in stroke, thrombosis and neointima formation. Here, we analyzed the role of FSAP in vascular remodeling processes related to arteriogenesis and angiogenesis in the mouse hind limb ischemia model.

Methods And Results: Femoral artery ligation was performed in mice and exogenous FSAP was injected locally to examine its effect on arteriogenesis in the adductor and angiogenesis in the gastrocnemius muscle over 21 days.

High drug load, stable, manufacturable and bioavailable fenofibrate formulations in mesoporous silica: a comparison of spray drying versus solvent impregnation methods.

Encapsulation of drugs in mesoporous silica using co-spray drying process has been recently explored as potential industrial method. However, the impact of spray drying on manufacturability, physiochemical stability and bioavailability in relation to conventional drug load processes are yet to be fully investigated. Using a 2(3) factorial design, this study aims to investigate the effect of drug-loading process (co-spray drying and solvent impregnation), mesoporous silica pore size (SBA-15, 6.