Study On Compound Sustained Release Tablets And Nasal Spray Of Oxycodone Hydrochloride

Oxycodone Hydrochloride is a pure opioid receptor agonist that had been used in clinical for almost 90 years and it is also a central nervous opioid analgesics that is semisynthesised by an alkaloid extracted from thebaine. Oxycodone Hydrochloride is similar to morphine in the structure, but has many features superior to morphine in pharmacology.As high bioavailability ,small side effects and other features,Oxycodone Hydrochloride had been widely used in the treatment of moderate to severe pain. In recent years, the international medical workers had paid attention to Oxycodone Hydrochloride in the treatment of cancer pain and developed many new formulations.Oxycodone Hydrochloride and Rotundine compound was developed independently by our country. Rotundine is an alkaloid extracted from China stepholidine. Rotundine is a dopamine (DA) receptor antagonist and its analgesic effect is as well as tramadol, but not addictive. As an analgesic drug, Rotundine is valid for all acute and chronic pain with hypnotic and stability and have no side effects such as nausea and vomit. Research had confirmed that Oxycodone Hydrochloride and Rotundine compounded by a certain percentage were able to improve analgesic effect on the synergies, while reducing adverse reactions such as addiction.First, the compound sustained-release table was screened and optimizated in this paper. Before the study, a reliable UV method was established to determination and content uniformity of Rotundine and Oxycodone Hydrochloride respectably. Then, a reliable HPLC method was established to determination the content of compound sustained-release tablets. Prescription study on the rapid release layer of Rotundine sustained-release tablets. Rotundine optimization followed by Oxycodone Hydrochloride preparation of sustained-release tablets, and the selected formulation and process was verified. Research shows that the compound sustained-release tablets prescription method is reasonable ,simple, reproducible and stable.In this paper, a nasal spray prescription is also screened and optimizated .First pH stability solution of the Oxycodone Hydrochloride was test and determined. Then, an method by using a sheep nasal in vitro is established to evaluate the transmucosa absorption of Oxycodone Hydrochloride with various absorption enhancers, and an effective absorption enhancer was found with the index of accumulative permeation. Further, the effects of different concentrations of this enhancer on the transmucosa absorption extent and the ciliotoxicity were investigated to determine the optimum amount of absorption enhancer. A HPLC method is also established to determination of Oxycodone Hydrochloride. The results showed : the enhancer found in the optimization of formulation could improve the accumulative permeation of Oxycodone Hydrochloride for 1.8 times by the sheep nasal absorption test.The method established is accurate, sensitive and the degradation products do not interfere with the main drug and excipient determination.