Development Of Compound Nefopam And Naproxen Sodium Sustained-release Capsules

Nefopam hydrochloride (Nefopam hydrochloride, Nef) is a new non-narcotic analgesics, doesn't have the properties of anti-inflammatory drugs, it also not a opioid receptor agonist. It's chemical structure belonging to the cyclization methyl of diphenhydramine, for the treatment of moderate and severe pain,also mild fever and skelaxin effect.Intramuscular injection 20mg this product may have the same effect of 12mg morphine. It has less inhibitory effect on respiration and don't has inhibitory effect on the circulatory system, non-tolerance and dependence. Commonly used clinically in the treatment of postoperative acute pain, acute pain medicine, chronic pain syndrome, cancer pain and so on. Naproxen sodium (Naproxen sodium, Npx-S) is a sodium of naproxen which is the aryl propionic acids of anti-inflammatory drugs.It has the fast absorption and more analgesic effect than naproxen.applied to a variety of mild to moderate pain. Such as toothache and other postoperative pain, dysmenorrhea, headache, also apply to rheumatoid arthritis, osteoarthritis,etc. Combination of two drugs can have synergetic effecties and enhance the analgesic effect and a powerful dual-link of antipyretic effect, non-addictive and less adverse reactions. In order to achieve the purpose of long-lasting and efficient analgesia, reduce side effects and low toxicity.Our experiment developed the compound sustained-release capsul of Nefopam and naproxen sodium (Referred to as compound FP), it is composed by the Nef sustained-release pellets and Npx-S enteric-coated sustained-release pellets.We choose HPLC to established a method that can analysis the two drugs once in vitro and in vivo. The results indicated that the method is simple and feasible, have a accurate and reliable data.At first,we use the extrusion-spheronization technology to prepared two drug-containing pellets.Than we use the fluidized bed coating technology to prepared the Nef sustained-release pellets and Npx-S enteric-coated sustained-release pellets.Nef sustained-release pellets which from the inside out containing drug-containing pellets and sustained-release layer two parts; Npx-S enteric-coated sustained-release pellets is composed of drug-containing pellets.sustained-release layer and enteric layer three parts. Fitting the release of two pellets model behavior, the Nef sustained-release pellets is in line with first-order kinetic equation and Npx-S enteric-coated sustained-release pellets is in line with the zero-order kinetic equation.Carrying out the pharmacokinetics study of FP on rats, we use the software to calculated pharmacokinetic parameters. The results showed that the compound preparation in rats consistent with the absorption of a single-chamber model.Through single-factor study, we use in vitro release test and orthogonal experimental to selected the best preparation method of extrusion-spheronization and fluidized bed coating technology.And compared to their general agents, two pellets have sustained-release effct and improved bioavailability.The study of relevance in vitro and in vivo, the regression equation of Nef sustained-release pellets and Npx-S enteric-coated sustained-release pellets with good correlation.