Influence of Enteric‐Coated Lactose on the Release Profile of 4‐Aminopyridine from HPMC Matrix Tablets

Abstract

A weakly basic experimental drug, 4‐aminopyridine, was taken as a model to study the influence of enteric‐coated lactose (EL) on the release profile from hydroxypropyl methylcellulose matrices. Powder mixtures were wet‐granulated with water. The dried granulation was compressed with a hydraulic press at 85 MPa. Dissolution studies were made using HCl 0.1 N and then phosphate buffer pH 7.4. Dissolution curves were described by M_t/M_inf = k*tⁿ. A trend toward increasing exponent (n) and decreasing release constant (k) values is observed with increasing EL concentrations up to 9%; this is attributed to an increasing obstruction of the diffusion path by isolated EL particles that are insoluble in HCl and are surrounded by a water‐filled space. After a critical EL concentration, the water‐filled spaces surrounding EL particles percolate, producing the opposite effect, increasing the release constant and decreasing the exponent (n) values as the EL proportion increases from 10% to 50%. EL particles (2% to 9%) decrease the drug and water transport in matrices dissolving in HCl. Thereafter, at pH 7.4, the pores formed by dissolution of EL particles produce the opposite. Both processes contribute to flattening the release profile. Release profiles with decreasing release constant values show a logarithmic trend toward increasing values of the exponent (n), changing from diffusion toward relaxation–erosion‐controlled processes.

Keywords:

• 4‐aminopyridine
• Release mechanism
• HPMC
• Sustained release
• Enteric‐coated lactose
• pH effect