Studies On Compound Paracetamol/Tramadol Hydrochloride Sustained-Release Capsules

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 paracetamol 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. To reduce the side effects and maintain relatively constant plasma concentration, the compound sustained-release capsules of twice daily administration were designed and prepared.According to the literature, Ultraviolet (UV) spectrophotometry method was developed for determination of content and drug release, respectively; High-performance liquid chromatography (HPLC) method with UV detection was applied to the plasma concentration of tramadol hydrochloride and paracetamol in dogs.Paracetamol pellets, whose content was about 80%, were prepared by means of power layering by the centrifugal coating and granulation equipment. Eudragit NE30D was used as coating materials and coating process was performed by the same equipment. The effects of process variables and formulation variables on coating pellets preparation were investigated. The results showed the coated pellets had a marked sustained-release property. The description of release profiles suggested that among the different kinetics, the first-order became the most appropriate model to describe release kinetics.Tramadol hydrochloride matrix sustained-release tablets were designed and prepared by using Compritol888 and ethyl cellulose(EC) as sustained-release material. The effects of process variables and formulation variables on matrix tablets preparation were investigated, as well as effects of interaction between two component in compound sustained-release capsules.Using self-made compound prompt-release tablets as the reference, the pharmacokinetics in dogs of compound sustained-release capsules were studied. The result of comparison between the compound sustained-release capsules and prompt-release tablets indicated that T_max and T_1/2 of paracetamol and tramadol hydrochloride was longer, whereas C_max was lower in former. Furthermore, the results showed that the compound sustained-release capsules had satisfactory sustained-release effects and there were good correlation between absorption percent in vivo and accumulative release in vitro.