Studies On Compound Acetaminophen Two-layer Sustained Release Tablets

Tramadol hydrochloride was widely used to the therapy of acute and chronic pain as its low side effects. Recently clinical research proved that the combination of tramadol hydrochloride and acetaminophen could provide analgesia equal to or greater than the sum of the components with a resultant reduction in the required dose of each agent and lead to reduced incidents of side effects as well. The two drugs produced analgesic activities through different mechanisms with tramadol having opiate-like properties and acetaminophen having prostaglandin inhibition properties. To reduce the side effects and maintain relatively constant plasma concentration, two-layer sustained release tablets of twice daily administration was designed and prepared by using hydroxypropyl methyl cellulose (HPMC) and octadecyl alcohol (OA) as basic matrix material.According to the literature, Ultraviolet (UV) spectrophotomatry method was developed for determination of physicochemical properties, content and drug release; High-performance liquid chromatography (HPLC) method with UV detection was applied to the plasma concentration of tramadol and acetaminophen in dogs. The extraction recovery of tramadol HC1 and acetaminophen was 97.95% and 97.01%, respectively.In the preformulation researches, the physicochemical properties of tramadol HC1 and acetaminophen were investigated, which benefit pharmaceutical design. Based on the researches of preformulation, single-factor tests were carried out to study the influences of formulation and manufacture process on the release of tramadol HC1 and acetaminophen, and two-layer tablets were prepared with HPMC and OA as the releasecontrolling material. Uniform design method as well as the fraction method were applied for the formulation optimization. The way of acetaminophen released from two-layer tablets could be described as non-Fickian diffusion, which was mainly by matrix erosion. And the release of tramadol followed Higuchi equation.Stability studies of preparation demonstrated that light, temperature, humidity and air had little effect on compound two-layer sustained release tablets.The studies of pharmacokinetics of compound two-layer sustained release tablets in dogs verified that the desired purpose of sustained release was achieved, which proved this formulation was successful. The plasma concentration maintained for about 24h. Its relative bioavailability was between 80.0% and 120.0%, The result of statistic analysis showed that tramadol HC1 and acetaminophen was bioequivalent with reference preparation. The release of tramadol HC1 and acetaminophen in vitro is correlative with the absorption fraction in vivo.