Novel dalfampridine-selective green potentiometric membrane sensors for in-line dissolution profiling of its extended release tablets

Abstract

Dissolution profiling of solid oral dosage forms is currently a mandatory analytical practice in pharmaceutical industry worldwide. Classically, this test is performed employing time-consuming, destructive and high waste generating conventional off-line separation-based techniques. Accordingly, this work is motivated with the ultimate objective of exploiting the unique capabilities of in-line potentiometric ion selective electrodes (ISEs) as greener alternative for monitoring the drug dissolution pattern. Novel Dalfampridine (FAM) potentiometric polyvinyl chloride (PVC) membrane sensors were fabricated with different cation exchangers, ionophores and plasticizers, and systematically optimized via comparing the sensors performance. Fabricated sensor based on potassium tetrakis (4-chlorophenyl) borate as cation exchanger plasticized with 2- nitrophenyl octyl ether and calix[6]arene as ionophore in a PVC matrix proved to possess high sensitivity with limit of detection of 1.78 × 10−5 mol L−1, a Nernstian slope of 57.40 mV/decade and fast response time within a concentration range of 2.0 × 10−5–1.0 × 10−2 mol L−1. Sensor performance was assessed as per IUPAC recommendation and applied successfully for determination of FAM in its pure form and Fampyra® tablets without the need for any sample pretreatments. Additionally, real time in-line monitoring of the dissolution profile of Fampyra® tablets using U.S Food and Drug Administration dissolution parameters was attained. Finally, the environmental impact of the proposed method was compared to a classical off-line HPLC dissolution strategy using newly developed tool for assessing method greenness; green analytical procedure index (GAPI).