盐酸阿夫唑嗪口崩片的制备及质量研究
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摘要
随着人民生活质量及健康水平的提高,人群的老龄化已成为趋势。良性前列腺增生症在老年人中发病率较高,已成为现代社会的一大棘手问题。对此症治疗方法的研究在不断发展和完善。法国圣德拉堡公司研制的α1-肾上腺素能受体阻滞剂阿夫唑嗪(Alfuzosin,商品名：桑塔),通过高选择性地阻断膀胱颈、前列腺包膜及其腺体、尿道等部位的肾上腺素能受体,使尿道张力降低,从而改善排尿状况。
口腔速崩片(Orally disintegrating tablets,简称ODT)是一种新型口服剂型。这种剂型不需用水或只需用少量水,无需咀嚼,片剂置于舌面,能迅速分散或溶解在唾液中,药物可通过口腔或食道内的黏膜吸收,生物利用度比普通制剂高,由首过代谢引起的副作用也可以减轻。口腔速崩片可在唾液中在几秒之内快速溶解,或在口腔内快速崩解。此种新颖剂型对儿童、老年、卧床不起和严重伤残病人最适宜。
本研究对阿夫唑嗪进行剂型优化,筛选合适工艺,制备成功了更适合老年人使用的口腔崩解片,并对其处方和工艺进行了探讨,得到优选处方中各成分的含量为：PVPP,10mg,甘露醇,50mg,MCC,30mg,硬脂酸镁,0.6%,微粉硅胶,1.2%,阿斯巴甜,0.5%,甜橙香精,0.5%。
同时,对阿夫唑嗪口腔崩解片进行体外溶出度特性分析,口感、崩解时间、溶出度、稳定性进行了考察,结果表明各指标均符合用药要求。更进一步确证了其优越性及适用性。
With the development of people's quality of life and health level, population aging has become a trend. The rate of Benign Prostatic Hyperplasia (BPH) is increasing, which becomes a very difficult question of current society. Research of finding new methods to cure this disease is going on, and a new al adrenoreceptor blocker manufactured by France LABORATOIRES SYNTHELABO, alfuzosin can lower urethral tension and improve urine flow by blocking the al adrenoreceptor in bladder neck, capsula prostatica, prostate and urethra.
Orally disintegrating tablets (ODT) is a new dosage for oral administration. When taking ODT, you need little or no water and chewing is unnecessary. Just place it on your tongue and it will disperse and dissolve in saliva. Then the drug is absorbed in mouth and esophagus, which results in higher bioavailability and reduced first pass effect. ODT can rapidly dissolve in saliva within seconds or disintegrate in mouth quickly, which is appropriate for children, old people and patients in bed.
This study optimized the formula of alfuzosin tablets, chose appropriate process after screening, prepared alfuzosin orally disintegrating tablets and discussed the formula and process. The optimal formula includes PVPP 10mg, mannitol 50mg, MCC 30mg,0.6percent of magnesium stearate,1.2 percent of silicon dioxide,0.5 percent of aspartame and 0.5 percent of sweet orange essence.
Dissolution in vitro of alfuzosin orally disintegrating tablets was analyzed. Investigation of taste, friability, disintegration time and dissolution demonstrated its pharmaceutical usage and it will be used widely.
口腔速崩片(Orally disintegrating tablets,简称ODT)是一种新型口服剂型。这种剂型不需用水或只需用少量水,无需咀嚼,片剂置于舌面,能迅速分散或溶解在唾液中,药物可通过口腔或食道内的黏膜吸收,生物利用度比普通制剂高,由首过代谢引起的副作用也可以减轻。口腔速崩片可在唾液中在几秒之内快速溶解,或在口腔内快速崩解。此种新颖剂型对儿童、老年、卧床不起和严重伤残病人最适宜。
本研究对阿夫唑嗪进行剂型优化,筛选合适工艺,制备成功了更适合老年人使用的口腔崩解片,并对其处方和工艺进行了探讨,得到优选处方中各成分的含量为：PVPP,10mg,甘露醇,50mg,MCC,30mg,硬脂酸镁,0.6%,微粉硅胶,1.2%,阿斯巴甜,0.5%,甜橙香精,0.5%。
同时,对阿夫唑嗪口腔崩解片进行体外溶出度特性分析,口感、崩解时间、溶出度、稳定性进行了考察,结果表明各指标均符合用药要求。更进一步确证了其优越性及适用性。
With the development of people's quality of life and health level, population aging has become a trend. The rate of Benign Prostatic Hyperplasia (BPH) is increasing, which becomes a very difficult question of current society. Research of finding new methods to cure this disease is going on, and a new al adrenoreceptor blocker manufactured by France LABORATOIRES SYNTHELABO, alfuzosin can lower urethral tension and improve urine flow by blocking the al adrenoreceptor in bladder neck, capsula prostatica, prostate and urethra.
Orally disintegrating tablets (ODT) is a new dosage for oral administration. When taking ODT, you need little or no water and chewing is unnecessary. Just place it on your tongue and it will disperse and dissolve in saliva. Then the drug is absorbed in mouth and esophagus, which results in higher bioavailability and reduced first pass effect. ODT can rapidly dissolve in saliva within seconds or disintegrate in mouth quickly, which is appropriate for children, old people and patients in bed.
This study optimized the formula of alfuzosin tablets, chose appropriate process after screening, prepared alfuzosin orally disintegrating tablets and discussed the formula and process. The optimal formula includes PVPP 10mg, mannitol 50mg, MCC 30mg,0.6percent of magnesium stearate,1.2 percent of silicon dioxide,0.5 percent of aspartame and 0.5 percent of sweet orange essence.
Dissolution in vitro of alfuzosin orally disintegrating tablets was analyzed. Investigation of taste, friability, disintegration time and dissolution demonstrated its pharmaceutical usage and it will be used widely.
引文
[1]刘忠国.阿夫唑嗪治疗前列腺增生症疗效观察[J].滨州医学院学报,1999；22(5)：459。
[2]刘敏,庄人通.阿夫唑嗪治疗良性前列腺增生症疗效观察[J].上海医药,1997,3：18-19。
[3]徐雯宇,严炎中,唐志华.治疗良性前列腺增生用药成本-效果分析[J].西北药学杂志,2004,19(1)：36-37。
[4]何忠芳,陈岚,王亚娟,等.口腔速崩片的研究进展及应用前景[J].兰州医学院学报,2003,29(1)：89-9。
[5]刘均洪,刘海洲,张媛媛,等.阿普唑仑口崩片的制备及质量检查[J].青岛科技大学学报(自然科学版),2008,29(2)：123-126。
[6]黄胜炎.分散片的进展[J].中医药学杂志,1992；27(4)：26
[7]雷同康.分散片的处方和工艺[J].中国医药工业杂志,1999,30(2)：87-90
[8]贾燕,许伟明.法莫替丁分散片的研制[J].中国医药工业杂志,1999,30(6)：251
[9]雷同康.硅胶型助流剂[J].药学通报,1986,21(9)：541
[10]戚海亮,张汝华.药物—预胶化淀粉研磨混合物体外溶出及提过溶出机理的研究[J].中国医药工业杂志,1991,22(11)：493。
[11]肖学成,卢源峰,谢云.布洛芬分散片的处方设计[J].中国医药工业杂志,1999,30(1)：21。
[12]BP.1980:755,779,849,859
[13]BP.1988:895；902；925
[14]BP.1980:734；736；753
[15]EP.1987:273005
[16]王卓,韩丽梅,张晓青,等.利用均匀论计筛选阿司匹林分散片处方[J].沈阳药科大学学报,1996；13(4)：235
[17]罗云,马红斌.扑热息痛分散片制备及质量控制[J].现代应用药学,1996；3：34。
[18]黄胜炎.口服固体速释制剂及其制备技术,中国医药工业杂志,2000,31(2)：84。
[19]奚念珠.药剂学,第二版。北京：人民卫生出版社。1989,82。
[20]专利US6080427[P][21] US 4886669; 1989。
[22]Eur Pat Appl 1989:365480 (CA1990; 113:178283j)。
[23]Eur Pat Appl 1994:599767 (CA1994; 121:65593g)。
[24]Brit 1981:2067900 (ca1982; 96:91643h)。
[25]Gabr Ke, El-Shaboury MH, Hashem FM. Alexandria J Pharn Sci, 1992; 6(1) (CA1992;117:55847c)。
[26]Eur Pat Appl 1998:281200(CA1989; 110:141578w)。
[27]方晓玲,杨敏,穆尼拉,等.几种新型辅料在速释片剂中的作用[J].中国医药工业杂志,2000,31(6)：257-259
[28]高春生,崔光华,等.速释固体制剂研究进展[J].国外医学—药学分册,1998,10：293-297。
[29]上海医药工艺研究所制剂实验室。药用辅料应用技术。北京：中国科技出版社,1991。
[2]刘敏,庄人通.阿夫唑嗪治疗良性前列腺增生症疗效观察[J].上海医药,1997,3：18-19。
[3]徐雯宇,严炎中,唐志华.治疗良性前列腺增生用药成本-效果分析[J].西北药学杂志,2004,19(1)：36-37。
[4]何忠芳,陈岚,王亚娟,等.口腔速崩片的研究进展及应用前景[J].兰州医学院学报,2003,29(1)：89-9。
[5]刘均洪,刘海洲,张媛媛,等.阿普唑仑口崩片的制备及质量检查[J].青岛科技大学学报(自然科学版),2008,29(2)：123-126。
[6]黄胜炎.分散片的进展[J].中医药学杂志,1992；27(4)：26
[7]雷同康.分散片的处方和工艺[J].中国医药工业杂志,1999,30(2)：87-90
[8]贾燕,许伟明.法莫替丁分散片的研制[J].中国医药工业杂志,1999,30(6)：251
[9]雷同康.硅胶型助流剂[J].药学通报,1986,21(9)：541
[10]戚海亮,张汝华.药物—预胶化淀粉研磨混合物体外溶出及提过溶出机理的研究[J].中国医药工业杂志,1991,22(11)：493。
[11]肖学成,卢源峰,谢云.布洛芬分散片的处方设计[J].中国医药工业杂志,1999,30(1)：21。
[12]BP.1980:755,779,849,859
[13]BP.1988:895；902；925
[14]BP.1980:734；736；753
[15]EP.1987:273005
[16]王卓,韩丽梅,张晓青,等.利用均匀论计筛选阿司匹林分散片处方[J].沈阳药科大学学报,1996；13(4)：235
[17]罗云,马红斌.扑热息痛分散片制备及质量控制[J].现代应用药学,1996；3：34。
[18]黄胜炎.口服固体速释制剂及其制备技术,中国医药工业杂志,2000,31(2)：84。
[19]奚念珠.药剂学,第二版。北京：人民卫生出版社。1989,82。
[20]专利US6080427[P][21] US 4886669; 1989。
[22]Eur Pat Appl 1989:365480 (CA1990; 113:178283j)。
[23]Eur Pat Appl 1994:599767 (CA1994; 121:65593g)。
[24]Brit 1981:2067900 (ca1982; 96:91643h)。
[25]Gabr Ke, El-Shaboury MH, Hashem FM. Alexandria J Pharn Sci, 1992; 6(1) (CA1992;117:55847c)。
[26]Eur Pat Appl 1998:281200(CA1989; 110:141578w)。
[27]方晓玲,杨敏,穆尼拉,等.几种新型辅料在速释片剂中的作用[J].中国医药工业杂志,2000,31(6)：257-259
[28]高春生,崔光华,等.速释固体制剂研究进展[J].国外医学—药学分册,1998,10：293-297。
[29]上海医药工艺研究所制剂实验室。药用辅料应用技术。北京：中国科技出版社,1991。
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