Light instability

Merrifield DR, Carter PL, Clapham D, Sanderson FD. Addressing the problem of light instability during formulation development. In Tonnesen HH. Photostability of Drugs and Drug Formulation. London Taylor and Francis, 1996 141-154. 

Hydroxocobalamin (vitamin another antidote, is a potential alternative to sodium nitrite treatment. It works by binding with cyanide to form nontoxic cyano-cobalamin (vitamin Bj ). Although effective and relatively safe in experimental models, the concentration available in the United States requires large infusion volumes and has a short shelf life due to light instability, and reports of anaphylactoid reactions have limited its use (8,13,21). Further studies using higher concentrations available in European formulations may eventually lead to its use as an outpatient alterative to sodium nitrite treatment in the United States (7,32). Other alternatives currently used or undergoing clinical trials in Europe include cobalt salts, limited by their toxicity, aldehydes, and aminophenol derivatives. These alternative treatments are not currently available in the United States (7). 

Chapter 13 Addressing the Problem of Light Instability during Formulation... 

THE PROBLEM OF LIGHT INSTABILITY DURING FORMULATION DEVELOPMENT 287... 

An intravenous infusion presentation offers considerable challenge to the formulation group because the problems associated with light instability will most closely resemble those of the drug substance. The drug is likely to be presented as a dilute... 

O.lN HCl solution in pyrex glass to sunlight caused a 40% drop of absorbance in 2 hours.A study of the pH dependency of the light instability showed a similar decline in absorbancy from pH 0.3 to 9, whereas above pH 11 the degradation was retarded.Again, it was found that solvents such as methanol, ethanol, dimethylformam-ide, ethylene glycol, and ether prevent or retard degradation. 

As an example, HDI is a highly crystalline diisocyanate, which forms spherulitic structures under moderate annealing conditions (room temperature, on the order of minutes) [41, 42], Unlike HS based for example on the chain extender 1,4-butanediol and diisocyanate MDI, the couple between 1,4 butanediol and the diisocyanate HDI imparts flexibility to the hard domain, which promotes the rate and extent of microphase segregation and may moderate the PUs plastic deformation behaviour. The use of an aliphatic diisocyanate, such as HDI, also circumvents issues related to thermal degradation and light instability usually associated with the aromatic hard domain [28, 41, 42], In addition, the high degree of crystaUinity in HDI lowers its susceptibility to hydrolytic attack. 

---