目的 制備眼用妥布霉素羧甲基殼聚糖微球，并評(píng)價(jià)其體外釋藥性能。方法 采用乳化-交聯(lián)固化法制備妥布霉素羧甲基殼聚糖微球，并以微球的收率、粒徑分布和包封率作為評(píng)價(jià)指標(biāo)，使用Box-Behnken實(shí)驗(yàn)設(shè)計(jì)優(yōu)化得到妥布霉素羧甲基殼聚糖微球的最優(yōu)處方。通過馬爾文激光粒度儀測(cè)定了微球的粒徑分布，掃描電鏡觀察其微觀結(jié)構(gòu)，考察微球在人工淚液中的釋藥性能。結(jié)果 優(yōu)化得到微球的處方組成：羧甲基殼聚糖質(zhì)量濃度為3.5%，甲醛質(zhì)量濃度為1.5%，Span-80質(zhì)量濃度為0.8%；妥布霉素羧甲基殼聚糖微球的平均粒徑為（12.3±0.4）μm，呈圓整球狀分布，無聚集；體外釋藥前期較快，后期較為緩慢，藥物釋放符合Higuchi釋藥模型。結(jié)論 通過使用Box-Behnken實(shí)驗(yàn)設(shè)計(jì)優(yōu)化制備得到妥布霉素羧甲基殼聚糖微球，制備工藝簡(jiǎn)易，重現(xiàn)性良好，具有較好的緩釋性能，可進(jìn)一步進(jìn)行實(shí)驗(yàn)研究。

Objective To prepare tobramycin-loaded carboxymethyl chitosan microspheres (Tob-loaded CMCMs) for ophthalmology and evaluate their in vitro release properties. Methods The Tob-loaded CMCMs were prepared by emulsification-crosslinking curing method. The yield, particle size distribution and encapsulation efficiency of microspheres were used as evaluation indexes. The BoxBehnken experimental design was used to obtain the optimal formulation of the Tob-loaded CMCMs. The particle size distribution of the Tob-loaded CMCMs was measured by Malvern laser particle size analyzer. The microstructure was observed by scanning electron microscopy. The in vitro release properties of the microspheres were investigated in artificial tears. Results The optimal formulation of the Tob-loaded CMCMs was optimized as followed:The carboxymethyl chitosan concentration was 3.5%, the formaldehyde concentration was 1.5%, the Span-80 surfactant concentration was 0.8%. The average particle size of Tob-loaded CMCMs was (12.3±0.4) μm, which had a regular spherical distribution and no aggregation. In vitro release was faster in the early stage and slower in the later stage, which was consistent with the Higuchi model. Conclusion The formulation of Tob-loaded CMCMs was optimized by Box-Behnken experimental design. The preparation process was simple, and the reproducibility was good. The Tob-loaded CMCMs could delay drug release, which laid the experimental foundation for animal experiments.

R945