Drug stability testing to support clinical feasibility investigations for intrathecal baclofen-clonidine admixture

Abstract

For a spinal cord injury patient, control of spasticity and bladder hyperreflexia can be obtained with the use of an intrathecal baclofen-clonidine admixture. The purpose of this study was to evaluate stability and compatibility of baclofen-clonidine admixtures in an implantable infusion system that could be used to treat patients. Implantable infusion systems and glass vials were filled with three different concentrations of admixture and maintained at 37°C for 16 weeks. Samples were collected every two weeks. Drug concentrations were determined using a validated high-performance liquid chromatography method. No modification of the physical appearance of the admixture was observed during the 16-week follow-up and the pH value variations were less than 0.5 units from those of initial samples. Until Week 14, both clonidine and baclofen concentrations were above 90% of the initial values. At Week 16, the drug concentrations had declined by more than 10% only in the implantable pump reservoir, but remained greater than 90% of the original concentration in all other vials. This study showed a good stability for both compounds until at least Week 14 and supports clinical feasibility investigations for intrathecal baclofen-clonidine admixture using implantable pump with refills every 12 or 14 weeks. This study also supports the idea that long-term studies of drug stability may be more accurate if performed in the pump rather than in glass vials.