本文選題：布洛芬 + 固體分散體　； 參考：《沈陽藥科大學(xué)學(xué)報(bào)》2017年05期

【摘要】：目的采用分子對(duì)接技術(shù)預(yù)測(cè)聚合物誘導(dǎo)的布洛芬固體分散體超飽和分子機(jī)制,并采用試驗(yàn)進(jìn)行驗(yàn)證,為選擇合理的輔料將布洛芬制成固體分散體提供依據(jù)。方法以PVP-K30、Soluplus、PVP-VA、HPMC-E5和HPMC-AS共5種常見制備固體分散體的載體為研究對(duì)象,首先,采用分子對(duì)接技術(shù)將布洛芬分別與5種載體進(jìn)行分子對(duì)接,預(yù)測(cè)藥物與載體分子間的相互作用;其次,將預(yù)測(cè)得到且與藥物結(jié)合比較穩(wěn)定的載體用來制備固體分散體,并采用差示掃描量熱分析法和紅外光譜法對(duì)固體分散體進(jìn)行表征,進(jìn)一步采用溶出度試驗(yàn)對(duì)方法的可行性進(jìn)行驗(yàn)證,從而闡明固體分散體穩(wěn)定性的機(jī)制。結(jié)果采用分子對(duì)接方法得到了5種輔料和藥物的結(jié)合能值,其中布洛芬分別與PVP-K30和Soluplus結(jié)合的能量較低,其結(jié)合能ΔG值分別為(-28.38±0.67)k J·mol-1和(-10.93±0.25)k J·mol-1,得出PVP-K30與布洛芬的結(jié)合能強(qiáng)于Soluplus。除此之外,溶出度驗(yàn)證試驗(yàn)結(jié)果顯示:不僅在p H值為1.2的溶出介質(zhì)中,以PVP-K30為載體的布洛芬固體分散體較Soluplus易溶出,而且在p H值為7.4的溶出介質(zhì)中,兩種布洛芬固體分散體在30 min時(shí)累積溶出量均達(dá)到85%,隨著試驗(yàn)時(shí)間的推移,Soluplus組累積釋放度降低,而PVP-K30組累積釋放度幾乎無變化,表明PVP-K30與布洛芬結(jié)合的穩(wěn)定性較Soluplus好,此驗(yàn)證結(jié)果與分子對(duì)接預(yù)測(cè)結(jié)果一致。結(jié)論通過分子模擬技術(shù)可以對(duì)固體分散體穩(wěn)定性分子機(jī)制進(jìn)行預(yù)測(cè),并篩選出PVP-K30作為制備布洛芬固體分散體的最佳輔料,為難溶性藥物選擇合適的輔料制成固體分散體提供了參考依據(jù)。
[Abstract]:Objective to predict the suprasaturation molecular mechanism of polymer induced ibuprofen solid dispersion by molecular docking technique, and to verify it by experiments, and to provide the basis for selecting reasonable excipients to prepare ibuprofen into solid dispersion. Methods five kinds of solid dispersion carriers, PVP-K30Soluplusus PVP-VAAHPMC-E5 and HPMC-AS, were used to prepare solid dispersions. Firstly, ibuprofen was docked with five carriers by molecular docking technique to predict the interaction between drug and carrier molecules. The solid dispersion was prepared by using the predicted carrier, which was stable in combination with the drug, and characterized by differential scanning calorimetry (DSC) and infrared spectroscopy (IR). The feasibility of the method was verified by dissolution test to clarify the mechanism of solid dispersion stability. Results the binding energies of five kinds of excipients and drugs were obtained by molecular docking method. The binding energies of ibuprofen to PVP-K30 and Soluplus were lower, and their binding energy 螖 G values were -28.38 鹵0.67kJ mol-1 and 10.93 鹵0.25kJ mol -1, respectively. The binding energy of ibuprofen and ibuprofen was higher than that of Soluplus. In addition, the results of dissolution verification test showed that ibuprofen solid dispersion with PVP-K30 as carrier was easier to dissolve than Soluplus, not only in dissolution medium with pH value of 1.2, but also in solvent with pH value 7.4. The cumulative dissolution of two ibuprofen solid dispersions at 30 min reached 850.The cumulative release rate of Soluplus group decreased with the passage of experimental time, but the cumulative release rate of PVP-K30 group was almost no change, indicating that the stability of the combination of PVP-K30 and ibuprofen was better than that of Soluplus. The results are in agreement with the predicted results of molecular docking. Conclusion the molecular mechanism of the stability of solid dispersion can be predicted by molecular simulation, and PVP-K30 is selected as the best adjunct for the preparation of ibuprofen solid dispersion. It provides a reference for the preparation of solid dispersions by choosing suitable excipients for dissolving drugs.
【作者單位】： 沈陽藥科大學(xué)藥學(xué)院;沈陽藥科大學(xué)制藥工程學(xué)院;
【分類號(hào)】：R943

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本文編號(hào)：1949315