| Part One Nimesulide, a new chiral nonsteroidal antiinflamma-tory drug and a COX-2 selective inhibitor, is used as curing the rheumatoid arthritis, osteoarthritis, respiratory inflammation, surgery-pain and fever. Tablets, granule preparations and dispersal preparations of nimesulide have been prepared in China. But when these drugs are taken orally its bio-half -life is short, and stomach and intestine reaction appear easily, which restrict its wide use in a degree. Sustained-release hollow suppositories whose apex-concentration is small and whose ill-reaction is short aren't reported. To determine the prescription of nimesulide suppositories and hollow suppositories, this article made use of orthogonal design. This kind of preparation that is hollow suppository reduces stomach and intestine reaction and delay bio-half -life. Objective: To complete the prescription of Nimesulide hollow suppositories and its preparation and quality control. Method: The composition of substance was selected by orthogonal design and the composition of hollow part was determined according to its dissolution in vitro. Hollow suppositories and suppositories were prepared and their content was determined by UV. In order to observe its dissolution in vitro, dissolution-percentage of hollow suppositories and suppositories was determined.Result: Orthogonal design was used by which dissolution percentage was target. The result of orthogonal design shows: Pa<0.05, Pb<0.05, Pc<0.05. There is no distinct difference that three standard of the proportion of two material Volume affects dissolution velocity, but that three standard of NIM content of Propylene affect dissolution velocity and that three standard of NIM content of Massa Estarinum A affect dissolution velocity must be taken into account, and there is statistical significance about their effect. Hollow part of hollow suppositories are one material which is Propylene and involves 50mg nimesulide and the other material which is Massa EstarinumA also involves 50mg nimesulide, but their volume is different. Material of suppositories is PEG400: PEG4000 : Glycerin=6:8:6. The outer-material of hollow suppositories is the same as material of suppositories. UV was employed for their content and the content of suppositories and hollow suppositories is 100.58±2.62mg and 100.89±1.45mg. The percentage of two preparation-released in vitro was measured and the result of analysis was carried out. Dissolution-percentage of suppositories were 17.5±1.7%, 37.7±3.1%,67.2±5.8%,81.9±8.4%,85.4±7.9%, 87.9±9.7%, 91.3±8.4%, 94.4±11.2% for 0.5, 1, 1.5, 2, 3, 4, 7, 10min and dissolution-percentage of hollow suppositories were 3.9±1.3%, 11.3±1.7%, 36.8 ±3.4%, 42.5±5.1%, 44.7±5.4%, 47.1±5.9%, 52.5±5.5%, 56.6±5.3%, 62.2±7.5%, 68.1±6.6%, 76.3±7.7%, 84.2±7.5%, 92.2±8.0% for 0.5, 1, 1.5, 2, 3, 4, 7, 10, 15, 20, 30, 45, 50min. Result of above-mentioned experiment showed suppositories dissolve rapidly and hollow suppositories dissolve rapidly at first and later dissolve slowly. Conclusion: The prescriptions of the hollow suppositories were reasonable.Part two How effective component of drugs absorb, matabolize and drain is important significance. In order to use drug in reason, this article developed pharmacokinetics hollow suppositories and suppositories in intro. Objective: To establish a method for the determination of nimesulide in plasma and to investigate the pharmacokinetics characteristics of nimesulide in rabbits after using tablets and suppositories and hollow suppositories. Method: To determine the content of nimesulide in plasma by HPLC. Parameters of pharmacokinetics of each rabbit were individually calculated with a 3p87 program. Result: A HPLC method using p-hydroxybiphenyl as the internal standard was developed for the determination of nimesulide in rabbit plasma. Chromatography of nimesulide was performed on a Hypersil ODS2 column (20cm×4.6nm ID 5um) using methanol-Water-acetic acid (60: 40: 1) as th... |
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