目的 制備添加了沉淀抑制劑的頭孢托侖匹酯超飽和自乳化釋藥系統(tǒng)（CEFP-S-SEDDSs）及其顆粒劑，并評(píng)價(jià)其質(zhì)量。方法 通過(guò)溶解度實(shí)驗(yàn)和偽三元相圖確定頭孢托侖匹酯自乳化釋藥系統(tǒng)（CEFP-SEDDSs）的處方組成及比例，并以羥丙基甲基纖維素（HPMC-E5）作為沉淀抑制劑，制備得到CEFP-S-SEDDSs；采用硅酸鋁鎂作為載體固化CEFP-SSEDDSs，并與其他輔料混合制備成CEFP-S-SEDDSs顆粒劑；評(píng)價(jià)CEFP-S-SEDDSs顆粒劑的理化性質(zhì)——熱力學(xué)穩(wěn)定性、自乳化效果、稀釋穩(wěn)定性、微觀形態(tài)；比較CEFP-S-SEDDSs顆粒劑和市售頭孢托侖匹酯顆粒劑的體外溶出度。結(jié)果 CEFPSEDDSs的處方組成：?jiǎn)蝸営退岣视王ィ∕aisine CC）為油相，15-羥基硬脂酸聚乙二醇酯（Solutol HS15）為乳化劑，二乙二醇單乙基醚（Transcutol HP）為助乳化劑，配比為6∶2∶2。CEFP-S-SEDDSs及其顆粒劑經(jīng)pH 1.2鹽酸溶液稀釋后均形成的微乳呈球狀，分散性良好，其形成的微乳粒徑分別為（104.6±3.7）、（139.5±3.8）nm，分散性指數(shù)（PDI）分別為（0.174±0.009）和（0.208±0.012），Zeta電位分別為（-13.6±0.6）mV和（-13.4±0.3）mV。CEFP-S-SEDDSs顆粒劑在pH 1.2鹽酸介質(zhì)溶液中溶出速度與市售頭孢托侖匹酯顆粒劑相當(dāng)；但當(dāng)介質(zhì)溶液pH值升高至6.8后，市售CEFP顆粒劑中的藥物濃度急劇下降，大量藥物以沉淀形式析出，CEFP-S-SEDDSs顆粒劑僅有少部分以沉淀形式析出。結(jié)論 CEFP-SSEDDSs顆粒劑能夠有效抑制因pH值變化而導(dǎo)致CEFP析出沉淀，有望促進(jìn)藥物充分吸收，提高藥物生物利用度

Objective To prepare cefditoren pivoxil supersaturated self-emulsifying drug delivery systems (CEFP-S-SEDDSs) and its granules, and to evaluate their properties. Methods The composition and proportion of CEFP-SEDDSs were determined by solubility test and pseudo-ternary phase diagram, and HPMC-E5 was used as a precipitation inhibitor to prepare CEFP-S-SEDDSs. The CEFP-S-SEDDSs granules were prepared by using aluminum magnesium silicate as a carrier and mixing with other excipients. The physicochemical properties (thermodynamic stability, self-emulsification effect, dilution stability, microstructure) of CEFP-SSEDDSs granules were evaluated. The in vitro dissolution of ceftoren pivoxil granules and CEFP-S-SEDDSs granules were compared. Results The formulation of CEFP-SEDDSs was composed of Maisine CC as the oil phase, Solutol HS15 as the emulsifiers, and Transcutol HP as the co-emulsifiers, with the ratio of 6:2:2. The microemulsions formed by CEFP-S-SEDDSs and its granules diluted with pH 1.2 hydrochloric acid solution were spherical and well dispersed. The particle size of the microemulsions formed by CEFP-S-SEDDSs and its granules were (104.6±3.7) nm and (139.5±3.8) nm, the PDI were (0.174±0.009) and (0.208±0.012), the Zeta potential were ( - 13.6±0.6) mV and ( - 13.4±0.3) mV, respectively. The dissolution rate of CEFP-SSEDDSs granules in pH1.2 hydrochloric acid medium solution was equivalent to that of cefditoren pivoxil granules, however, when the pH value of the medium solution increases to 6.8, the drug concentration in commercially available CEFP granules sharply decreases, and a large number of drugs precipitate in the form of precipitation, and only a small portion of CEFP-S-SEDDSs granules precipitate in the form of precipitation. Conclusion CEFP-S-SEDDSs granules can effectively inhibit the precipitation of CEFP caused by pH changes, which is expected to promote full drug absorption and improve drug bioavailability.

R944.2

咸陽(yáng)職業(yè)技術(shù)學(xué)院科研項(xiàng)目（2023SKB01）