A new pressure-controlled colon delivery capsule for chronotherapeutic treatment of nocturnal asthma

作者：Barakat Nahla S; Al Suwayeh Saleh A; Taha Ehab I; Yassin Alaa Eldeen Bakry^*

来源：Journal of Drug Targeting, 2011, 19(5): 365-372.

DOI：10.3109/1061186X.2010.504264

• Colon delivery
• nocturnal asthma
• theophylline
• Eudragit coating
• colon luminal pressure

The purpose of this study was to prepare a pressure-controlled colon delivery capsule (PCDC) containing theophylline (TPH) dispersion in a lipid matrix as a chronotherapeutic drug delivery system for the treatment of nocturnal asthma. The system was made by film coating using Eudragit S100- based formula over the sealed-hard gelatin capsules containing the drug-lipid dispersion. The lipid formula was composed mainly of Gelucire 33/01 (G33) with different ratios of surfactants (1-10%). The efficiency of the prepared system was evaluated in vitro for its ability to withstand both the gastric and intestinal medium. In addition, the drug plasma concentrations were monitored after single administration to Beagle dogs and compared to that obtained after administration of a reference marketed, generic, sustained-release TPH tablets, Avolen (R) SR. It was found that the optimum lipid formula was GL2 containing 90% G33 and 10% Labrasol. The film-coated capsules showed complete resistance to both the acidic environment (pH 1.2) for 2 hours and phosphate buffer pH 6.8 for 3 hours at 37 degrees C. In vivo evaluation of the TPH-based PCDCs showed longer lag time compared TO the marketed formula followed by sudden increase in TPH blood levels, which recommends the high potential of this system as a chronotherapeutic drug delivery for nocturnal asthma. The prepared PCDCs exhibited a significantly higher C(max) and T(max) and a nonsignificantly different AUC compared with Avolen (R) SR. Higher TPH blood levels from 1 to 8 hours postadministration was detected in the case of the prepared PCDCs.

• 出版日期2011-6