【摘要】：微球劑型是目前制劑研究的重點(diǎn)方向之一。微球可以降低藥物的降解速率,提高藥物的穩(wěn)定性。單一交聯(lián)劑制備的微球具有良好的緩釋性,但其不能實(shí)現(xiàn)有效的控釋。本文采用京尼平與香草醛復(fù)配交聯(lián)制備5-氟尿嘧啶載藥微球,通過(guò)調(diào)節(jié)交聯(lián)劑的比例控制微球的釋放速度。本課題首先通過(guò)對(duì)單一交聯(lián)劑制備微球的條件進(jìn)行篩選。在該條件的基礎(chǔ)上,確定了復(fù)配交聯(lián)劑制備微球的最佳條件,最后加入5-氟尿嘧啶制備載藥微球,利用HPLC測(cè)定載藥微球的最高載藥量為2.97%,包封率為20.27%。通過(guò)SEM圖譜表征,制備的微球分散性良好,粒徑分布均勻,粒徑范圍為10-20μm左右;FT-IR圖譜結(jié)果顯示,京尼平和香草醛均與殼聚糖交聯(lián);溶脹性能結(jié)果顯示,不同復(fù)配比例交聯(lián)劑制備的微球溶脹率不同,證明不同復(fù)配比例交聯(lián)劑制備的微球具有不同的釋放速率;XRD圖譜結(jié)果顯示,微球成功交聯(lián);DSC-TGA圖譜證實(shí)了5-氟尿嘧啶在微球內(nèi)部,并提高了5-氟尿嘧啶的穩(wěn)定性。參考已有的國(guó)家標(biāo)準(zhǔn),研究了5-氟尿嘧啶載藥微球的釋放性能,在pH=3.6緩沖溶液中,微球在24 h內(nèi)最高累積釋放率為97.2%,在pH=7.4緩沖溶液中,微球在24h內(nèi)最高累積釋放率為94.2%。因此,通過(guò)控制交聯(lián)劑復(fù)配比例可以達(dá)到控制釋放速率的效果。在高溫、高光和高濕條件下對(duì)微球的穩(wěn)定性進(jìn)行了研究,證明5-氟尿嘧啶微球的穩(wěn)定性良好。
[Abstract]:Microsphere dosage form is one of the key directions of the present preparation. The microspheres can reduce the degradation rate of the medicine and improve the stability of the medicine. The microspheres prepared by the single cross-linking agent have good slow-release property, but can not realize effective controlled release. In this paper,5-fluorouramide drug-loaded microspheres were prepared by cross-linking of Beijing-Niping and vanillin, and the release rate of the microspheres was controlled by adjusting the cross-linking agent. In this paper, the conditions of the preparation of microspheres by a single cross-linking agent are selected. On the basis of this condition, the optimal conditions for preparing the microspheres by the compound cross-linking agent were determined, and the drug-loaded microspheres were prepared by adding 5-fluorouramide. The highest drug-carrying amount of the drug-loaded microspheres was 2.97% and the encapsulation rate was 20.27% by HPLC. The prepared microspheres have good dispersivity and uniform particle size distribution, and the particle size range is about 10-20 & mu; m; and the FT-IR spectrum results show that both the Jingyi and the vanillin are cross-linked with the chitosan; and the swelling performance results show that the swelling rate of the microspheres prepared by the cross-linking agent of different compounding proportions is different, The results show that the microspheres have different release rates. The results of the XRD pattern show that the microspheres were successfully cross-linked, and the DSC-TGA pattern confirmed that the 5-fluorouramide was inside the microspheres, and the stability of the 5-fluorouramide was improved. With reference to the existing national standard, the release performance of 5-fluorouramide drug-loaded microspheres was studied. The maximum cumulative release rate of the microballoon was 97.2% in the buffer solution of pH = 3.6, and the maximum cumulative release rate was 94.2% in the buffer solution of pH = 7.4. Therefore, the effect of controlling the release rate can be achieved by controlling the compounding ratio of the cross-linking agent. The stability of the microspheres was studied under the conditions of high temperature, high light and high humidity.
【學(xué)位授予單位】：河北科技大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：TQ460.1;O636.1

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