Pharmaceutical development and technology

A novel pH-dependant and double crosslinked polymethacrylate-based polysphere matrix for enteric delivery of isoniazid.

PMID 22591035


This study aimed at developing double crosslinked isoniazid (INH)-loaded polymethyl-methacrylate-ethylcellulose (PMMA-EC) polyspheres for rate-controlled enteric drug delivery. A PMMA solution was manipulated with the addition of EC to produce polyspheres by drop-wise extrusion into a primary crosslinking solution of AlCl3 (25% w/v), before adding a second crosslinking solution of either 30% w/v BaCl2 (polysphere Batch A) or 30% w/v MgCl2 (polysphere Batch B). The polyspheres were then subjected to FTIR spectroscopic analysis, in vitro drug release studies, drug entrapment efficiency (DEE) determination as well as surface area and porositometric investigations. Molecular Mechanics (MM) simulations elucidated the interaction between the cations and the PMMA-EC combination. FTIR spectra revealed an affinity of PMMA for Ba(2+), Mg(2+) and Al(3+). SEM showed smooth robust polyspheres ranging between 4-6 mm. Porositometric analysis established that polysphere Batch A had larger pores (315.314 Åabs) than Batch B (234.603 Åabs). Drug release profiles from polysphere Batch A displayed burst release with 50% INH released within 2 h (N = 3) that was attributable to the larger ionic radius of the second crosslinker Ba(2+) compared Mg(2+) which was employed for polysphere Batch B. The latter produced polyspheres with superior control in INH release (<25% within 2 h) (N = 3) and a higher DEE with minimal pore formation. The experimental findings were well corroborated by the MM simulations.