Varshosaz J, Tabbakhian M, Zahrooni M
Department of Pharmaceutics, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.
J Microencapsul. 2007 May;24(3):253-62. doi: 10.1080/02652040601162723.
Cinnarizine (CN) is a pipperazine derivative with anti-histaminic activity and high affinity to H(1) receptors. The objective of this study was to produce floating microspheres (FM) of CN by diffusion solvent evaporation technique to increase drug solubility and hence its bioavailability. The effect of process variables such as: Eudragit type, stirring rate and time of stirring after addition of oily phase to the aqueous phase were evaluated on the yield, particle size, loading, release and floating behaviors of microspheres using a factorial design. Release of CN from microspheres was studied in pHs: 1.2 and 7.2 using paddle technique. The samples of dissolution test were analysed spectrophotometrically at 256.1 nm and 256.5 nm respectively. particle size of microspheres was studied using microscopic method and their floating behavior was studied in HCl (0.1 N, pH 1.2) medium with Tween 20 (0.5% w/v). Eight formulations were produced by changing 3 variables each at 2 levels: Eudragit S100 (Ps) or a combination of two Eudragits S100:RLPO (1:3) (P(SR)), stirring rate of 200 (R(2)) or 300 rpm (R(3)) and stirring time after addition of oily phase to the aqueous phase 0 (T(0)) or 1 hr (T(1)). The average size of microspheres was 300 microm. The highest yield efficiency (94%) was seen in P(SR)R(3)T(0) formulation and the greatest loading percentage was 8.5% in P(SR)R(2)T(1) formulation. The microspheres containing just Eudragit S100, didn't show suitable releasing profile during 8 hours in pH 1.2 but those containing combination of Eudragit S100:RL released approximately whole amount of CN during 10 hours (8 hours in pH 1.2 and 2 hours in pH 7.2). The highest floating percentage up to 6 hours was 77.5% in P(S)R(2)T(1) formulation. The type of Eudragit used seems to play an important role in producing sustained release floating microspheres. P(SR)R(3)T(0) formulation containing both types of Eudragit S100:RL (1.3) that releases 99.1% of the drug after 10 hours and 65% floating after 6 hr seems suitable for oral sustained delivery of CN.
桂利嗪（CN）是一种具有抗组胺活性且对H(1)受体具有高亲和力的哌嗪衍生物。本研究的目的是通过扩散溶剂蒸发技术制备桂利嗪的漂浮微球（FM），以提高药物溶解度，从而提高其生物利用度。使用析因设计评估工艺变量如：Eudragit类型、搅拌速率以及油相加入水相后的搅拌时间对微球的产率、粒径、载药量、释放度和漂浮行为的影响。使用桨法在pH值为1.2和7.2的条件下研究桂利嗪从微球中的释放情况。溶出度测试样品分别在256.1nm和256.5nm处用分光光度法进行分析。使用显微镜法研究微球的粒径，并在含有吐温20（0.5%w/v）的HCl（0.1N，pH1.2）介质中研究其漂浮行为。通过在两个水平上分别改变3个变量制备了8种制剂：Eudragit S100（Ps）或两种Eudragit S100:RLPO（1:3）的组合（P(SR)）、搅拌速率为200（R(2)）或300rpm（R(3)）以及油相加入水相后的搅拌时间为0（T(0)）或1小时（T(1)）。微球的平均粒径为300微米。在P(SR)R(3)T(0)制剂中观察到最高产率效率（94%），在P(SR)R(2)T(1)制剂中最大载药百分比为8.5%。仅含有Eudragit S100的微球在pH1.2条件下8小时内未显示出合适的释放曲线，但含有Eudragit S100:RL组合的微球在10小时内（在pH1.2条件下8小时，在pH7.2条件下2小时）释放了几乎全部的桂利嗪。在P(S)R(2)T(1)制剂中，高达6小时的最高漂浮百分比为77.5%。所用Eudragit的类型似乎在制备缓释漂浮微球中起重要作用。含有两种Eudragit S100:RL（1.3）类型且在10小时后释放99.1%药物并在6小时后漂浮65%的P(SR)R(3)T(0)制剂似乎适合桂利嗪的口服缓释给药。
