Development of a Novel Drug Release System, Time-Controlled Explosion System(TES). II. Design of Multiparticulate TES and in Vitro Drug Release Properties.

Abstract

For the design of multiparticulate Time-Controlled Explosion System (TES), the thickness of the swelling agent layer was optimized by determining the amount of drug released. Low-substituted hydroxypropylcellulose (L-HPC) was used as a swelling agent. At 120 μm thickness, tiapride hydrochloride was released before the membrane destruction, while at 180 μm thickness the drug release was completed within 30 min after the destruction. Similar results were obtained for TES containing metoclopramide hydrochloride. These results suggest that the L-HPC layer must be at least 180 μm thick. To evaluate the effect of solubility of the drug on release behavior, sodium diclofenac and nilvadipine were used as typical model drugs with an acidic functional group and poor solubility, respectively. The release studied were performed for these drugs in TES with 180 μm L-HPC layer. It is demonstrated that TES can provide a constant drug release profile, regardless of the solubility of a drug and dissolution conditions. In the case that L-HPC layer was fixed at a thickness of 180 μm, the release of diclofenac was not influenced by drug content.