Joseph Ballard Bogardus

Chemical and Physical Stability of Chimeric L6, a Mouse−Human Monoclonal Antibody

Chimeric L6 is a mouse–human monoclonal antibody specific for tumor cell-associated antigens. The factors affecting the physical and chemical stability of chimeric L6 were assessed at elevated temperatures (30–60°C) and by multiple freezing and thawing. Three routes of degradation were observed: chemical degradation to smaller molecular weight species, irreversible aggregation, and formation of a reversible dimer. The specific pathway depended on the stress condition applied and the pH, with maximal overall stability to both thermal stress and multiple freezing/thawing observed at about pH 5.5. Other factors including antibody concentration, buffer concentration, NaCl concentration, and agitation had minimal influence on the stability. Commonly used sugars, polyhydric alcohols, and amino acids effectively prevented freeze/thaw-induced aggregation.

Pharmaceutical relationships of three solid state forms of stavudine

Three solid state forms of stavudine designated forms I, II and III have been identified and characterized. Forms I and II are anhydrous polymorphs whereas form III is hydrated and is pseudopolymorphic with forms I and II. Physico-chemical and thermodynamic properties of the three solid state forms have been characterized. Solid-state stability and potential for interconversion of the forms to aid in the selection of preferred form for development and commercialization has been studied. Conditions of recrystallization governing the formation of thermodynamically most stable polymorphic form I devoid of other forms was identified.

Stabilization of Chimeric BR96-Doxorubicin Immunoconjugate

Chimeric BR96-doxorubicin conjugate (BR96-DOX) is an immunoconjugate designed to specifically target and kill certain tumor cells. The linker between the chimeric BR96 antibody and DOX is an acid-labile hydrazone group which was designed to undergo lysosomal hydrolysis to release DOX in vivo. Stability studies indicated that acid-catalyzed hydrazone hydrolysis was the major degradation route in vitro. Even under optimal conditions of pH and temperature, the stability of BR96-DOX in solution was not acceptable for long-term storage. Lyophilization of BR96-DOX in the presence of added sugars, such as lactose or sucrose, and subsequent storage of the lyophile under refrigeration significantly improved the stability. Therefore lyophilization appears to be a viable approach for achieving long-term stabilization of BR96-DOX.