Studies On Preparation Of The Ketoprofen-Ploybutylcyanoacrylate-Nanoparticles And It's Pharmacokinetics

Ketoprofen (KP) is one of the non-steroidal anti-inflammatory drug (NSAID), antipyrexia and analgesia drugs, which used to be used to cure the arthritis deformans, spondylitis and to relieve pain clinically. KP can be absorbed very quickly after oral administration. The peak concentration of the KP in plasma can reach in about 0.5²h after oral adiminstration. But the KP in plasma can be eliminated very quickly. And the T_1/2 of the KP in plasma is about 2³h. So that the oral administration of the KP will be performed several times (about 3⁴ ) a day to heal diseases. But the KP has the charictaristics of stimulation to the gastrointestinal tract, so the mucosa of the gastrointestinal tract will be damaged if the KP is be oral administrated frequently.PACA has many useful characteristics such as little toxic side effect, biocompatibility and biodegradation. The PACA-NP, which is used to be the drug carries has the organ targeting, and the drugs loaded the PACA-NP can be sustained realeased controlled.In this paper, KP- PACA-NP was prepared with a two-step method and the preparation conditions were optimized. The destination of the study is to achieve the intravenous infectable KP praeparatum. Not only the KP can be sustained realeased controlled from the KP- PACA-NP, but also the mucosa damages of the gastrointestinal tract by the KP can be avoided.The experiments are described as follows. The PBCA—NP had been prepared with the emulsion polymerization method refer to several references. The preparation conditions were optimized with the orthogonal-design experiments of L₉ (3⁴) according to the grain size of the PBCA—NP. The pH2³,1.0% of the Pluronic F68 and 1.0¹.5% of the Dextran were the optimum conditions. In this condition, the average grain size of the PBCA —NP was about 50nm. Then the KP—PBCA—NP was preparated with the adsorptive process. And the preparation conditions of the KP—PBCA—NP were optimized with the uniform design of U₁₀ (10⁸) according to the entrapment efficiency and the quantity ofdrug-load. When the pH, PBCA and KP were about 1, 0.5% and 0.8mg ? ml"1 respectively the entrapment efficiency about 95.64% and the quantity of drug-load about 15.32% were achieved. The releasing experiment of the KP—PBCA—NP in vitro was performed. The release regularity of the KP—PBCA—NP is corresponded with the equation of Logistic.The equation is Y=------83/7080------- and ^ correlation coefficient is 0.9972.1 + 12.2521*-0-4137*The rabbit injected with yeast was injected with the KP—PBCA—NP immediately. Then the blood of the rabbit was extracted from the ear marginal veins and rectal temperature of the rabbits was determinated simultaneously. The Percent inhibition (E) vs time (T) profiles of KP —PBCA —NP and the plasma concentration of the KP vs time(T) profiles following iv the KP—PBCA—NP were drawed. And the Pharmacokinetics parameters of KP—PBCA—NP were calculated. From the profiles, it can be concluded that the KP was sustained released from the KP —PBCA —NP. A correspondent high concentration of the KP in the blood could be hold, so the rising of the body temperature of the rabbit could be inhibited efficiently for a long time.If the method that the KP—PBCA—NP had been preparated firstly and then the KP— PBCA—NP was infected to the rabbit had been employed, not only the damages of the mucosa of the gastrointestinal tract because of the oral administration praeparatum of KP would be avoided but the KP would be sustained released. It provides a very good idea about the praeparatum of KP for us, and it has a good potential of clinical application.