| Objective: Nonsteroidal antiinflammatory drugs (NSAIDS) are frequently used in clinic,and most of them are chirality drugs.Because of many NSAIDS adverse reactions ,they should be used from small dosage and be avoided from using large dosage and for long term as far as possible.Ketoprofen is one of NSAIDS with 2-phenolethylformic acid,which have a chirality center and are generally used with racemic bodies in clinic.But only dextral bodies have action of antiinflammation, antirtheumatism and analgesia. Right-handed rotation ketoprofen (S-KP) went first on the market in Spain in 1996, which is used with trometamol salt. The characteristics of S-KP is little dissolvable in water, slow in absorption and heave toxicity in gastrointestinal tract, which influence its clinical prospect.The clathrate from S-KP andβ-Cyclodextrin (β-CD) can be dissolved more easily in water, absorb faster and more completely. S-KP-β-CD microspheres is eliminated lowest and the half life of it is longer ,and to reduce dosing times and gastrointestinal stimulation, the development of sustained-released microspheres of S-KP-β-CD augment its administration pathways in clinic.Methods: The clathrate from S-KP and β-CD was prepared. S-KP-β-CD was analyzed by microscope, IR and NMR. The pharmacokinetics of S-KP-β-CD microspheres was researched in rabbits in vivo. Furthermore the preparation techniques and dissolubility of S-KP-β-CD microspheres were filtered by uniformity design with the matrix of gelatin and acacia. Results: 1.The inclusion (S-KP:β-CD=1:3) prepared by sedimentation method was examined by 3 methods to find that S-KP was almost dispersed in molecules.2.The inclusion microspheres bioavailability were improved. The pharmacokinetics data of inclusion microspheres, Cmax, Tmax, AUC0-24 were 4.060μg · ml-1,2.250h , 29.883μg·h·ml-1 respectively, while these of original drugs were 4.210 μg · ml-1, 1.030h, 13.164μg·h·ml-1. And relative bioavailability of S-KP-β-CD microspheres was 2.2699.3.The data of best preparation techniques of S-KP-β-CD sustained-released microspheres filtered by uniformity design was 4.0% in gelatin concentration, 0.24-0.60% in emulsificator usage,1.0h in solidifying time, 28.69% in mean microsphere drug content, 47% in mean loading drug, 94.98% in mean trap efficiency, 51.16μm in meansize, over 95% in mean size distribution (12.8-96.0μm) .4.The microspheres average m was 1.12 and 0.84 in artificial gastric and intestinal liquid respectively, and that of original drugs was 1.46 and 0.59 in artificial gastric liquid was 113.93min and 18.54min, while that of original drugs was 38.86min and 3.56min in artificial gastric and intestinal liquid respectively. Moreover the average T50 of microspheres was 84.68min and 111.69min, while original drugs T50 was 30.17min and 1.87min in corresponding mediums respectively. The dissolubility parameters of microspheres in vitro were significantly different from that of original drugs in different mediums and the dissolubility parameters of microspheres in artificial gastric and intestinal liquid were significantly different from those in the same mediums by analysis of variance.Conclusions:The S-KP-β-CD clathrate microsphere bioavailability was improved and sustained-released significantly in vivo and in vitro...
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