Colon-specific drug delivery for mebeverine hydrochloride.
Mebeverine Hydrochloride (MB-HCl), an effective spasmolytic drug, was formulated as CODES. A colon-specific drug delivery technology CODES was designed to avoid the inherent problems associated with pH- or time-dependent systems. To achieve more protection and control of drug release, MB-HCl was prepared as microspheres and compressed as core tablets of CODES (modified CODES). The core tablets contained the drug either in free form [Formula 1 (F(1))], or as microspheres with 2 different polymer:drug:lactulose ratios (1:1:0.5 [Formula 2 (F(2))] and 2:1:0.5 [Formula 3 (F(3))]. The release profiles of the coated CODES systems were compared with uncoated compressed tablets. The uncoated tablet showed a drug release of 94% after 1 h in simulated gastric condition (pH = 1.2). The release characteristics of the coated systems revealed that the enteric coating (Eudragit L(100)) prevented any drug release in simulated gastric or duodenal conditions in the first 3 h (pH 1.2-6.1), after which drug was slightly liberated in simulated intestinal fluid (pH 7.4) {Phase 1 (P1)}. After 4 h the pH was adjusted to 7 and beta-glucose-oxidase was added, which is an enzyme produced by enterobacteria present in the colon. The acid-soluble coat (Eudragit)E(100)) dissolved and the drug release suddenly increased to reach 95, 72 and 60.4% for F(1)-F(3), respectively. IR spectrum study showed a covalent bond between the drug and the polymer in the formulae F(2) and F(3) resulting in the sustained drug release from the microspheres with a significant difference (p>0.05) to F(1). The findings were confirmed by in vivo investigation using X-ray images for Guinea pigs ingested tablets containing barium sulphate (F(4)), where the tablet began to disintegrate after 10 h of tablet intake. The results of the study indicated that MB-HCl CODES colon-specific drug delivery can act as a successful trigger for drug targeting in the colon. Furthermore, a sustained release of the drug can be achieved from modified CODES containing the drug in the form of microspheres.
Department of Pharmaceutics, Faculty of Pharmacy, King Saud University, Riyadh KSA, Saudi Arabia. omarsamia@hotmail.com
Samia
S
Omar
Basmah
B
Aldosari
Hanan
H
Refai
Omaimah Al
OA
Gohary
D000818:Animals; D003106:Colon / Q000378:metabolism*; D016503:Drug Delivery Systems; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D008863:Microspheres; D010627:Phenethylamines / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013607:Tablets
D010627:Phenethylamines; D013607:Tablets; C005096:mebeverine