Dissolution-Controlled Salt of Pramipexole for Parenteral Administration: In Vitro Assessment and Mathematical Modeling

Abstract

Parenteral suspensions of poorly water-soluble salts for intramuscular administration retain therapeutic drug concentration over a long duration. In vitro drug dissolution testing is a prerequisite to assess batch-to-batch variability as well as to assure appropriate drug release during formulation development. The purpose of the present work was to compare the drug release kinetics of two salts of pramipexole in powdered and suspension forms. The two salts employed for the dissolution study were commercially available soluble salt-pramipexole dihydrochloride monohydrate (PRP HCl) and in-house synthesized poorly water-soluble salt, pramipexole pamoic acid salt (PRP PAM). Modified USP apparatus 2 (paddle) using dialysis sac and open loop USP apparatus 4 (flow-through cell) were used for the in vitro dissolution studies. The drug release was estimated using high-performance liquid chromatography. The release kinetics were statistically analyzed using various mathematical models. Results obtained from in vitro dissolution testing showed an immediate-release profile for PRP HCl and a sustained-release profile for PRP PAM, indicating its long-acting potential. The developed method could discriminate between different particle sizes of the PRP PAM salt. The results indicated that the release profile of the PRP PAM salt using modified USP apparatus 2 with dialysis sac more closely mimicked the desired in vivo conditions of intramuscular administration as compared to open loop USP apparatus 4. The developed dissolution method can be used as a quality control tool for PRP PAM injectable suspension.