Developing a Biorelevant Dissolution Method for an Extrudable Core System (ECS) Osmotic Tablet.

The objective of this work is to develop a biorelevant dissolution method to support the clinical study for In Vitro In Vivo Correlation (IVIVC) of the first commercially approved single-layer extrudable core system (ECS) osmotic tablet - the 11 mg tofacitinib modified-release tablet. The dissolution conditions were selected through analysis of experimental work including several designed experiments (DoE). The Apparatus 2 (paddles) was selected over the Apparatus 1 (baskets) to minimize the dissolution test variability.

Development and validation of a Level A in-vitro in-vivo correlation for tofacitinib modified-release tablets using extrudable core system osmotic delivery technology.

Purpose: To determine if a validated Level A in-vitro in-vivo correlation (IVIVC) could be achieved with the extrudable core system (ECS) osmotic tablet platform. Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis.

Methods: Fast-, medium-, and slow-release modified-release formulations of 11 mg tofacitinib ECS tablets, and one formulation of 22 mg tofacitinib ECS tablet, were manufactured.

Use of Activated Carbon in Packaging to Attenuate Formaldehyde-Induced and Formic Acid-Induced Degradation and Reduce Gelatin Cross-Linking in Solid Dosage Forms.

Formaldehyde and formic acid are reactive impurities found in commonly used excipients and can be responsible for limiting drug product shelf-life. Described here is the use of activated carbon in drug product packaging to attenuate formaldehyde-induced and formic acid-induced drug degradation in tablets and cross-linking in hard gelatin capsules. Several pharmaceutical products with known or potential vulnerabilities to formaldehyde-induced or formic acid-induced degradation or gelatin cross-linking were subjected to accelerated stability challenges in the presence and absence of activated carbon.

A mechanism for the formation of bis-glutathione conjugates of propargyl alcohol.

Our earlier research clearly revealed glutathione (GSH) conjugation as a major pathway for the metabolism of propargyl alcohol (2-propyn-1-ol) in rats and in mice. The identification of the metabolite 3,3-bis[(2-acetylamino-2-carboxyethyl)thio]-1-propanol (I) and its congeners represented the first example of multi-glutathione addition to a triple bond, and invoked further research to determine the mechanism for bis-conjugation. To determine whether GSH conjugated directly with propargyl alcohol or after oxidation of the latter to 2-propynal, urinary metabolites from rats administered deuterium-labeled propargyl alcohol were characterized.