CN107957381A - 一种螺内酯片剂溶出度的测定方法 - Google Patents
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Abstract
本发明涉及一种药物固体制剂体外溶出度的测定方法,特别涉及一种螺内酯片剂溶出度的测定方法,所述方法,步骤如下:步骤1,配制15L溶出介质,分别取螺内酯仿制片和原研片各12片,投入12杯的智能溶出仪中,设置方法:浆法75r/min,1000ml为溶出体积,取样点分别为10min、15min、20min、30min、45min、60min、90min、120min。步骤2,分别于上述取样点取样进行螺内酯溶出量测定,比较两种片剂每个取样点的溶出量,计算f2因子。
Description
技术领域
本发明涉及一种药物固体制剂体外溶出度的测定方法,特别涉及一种螺内酯片剂溶出度的测定方法。
背景技术
螺内酯。化学名称:17β-羟基-3-氧-7a-(乙酰硫基)-17a-孕甾—4—烯—21—羧酸Y—内酯。主要功效为:
(1)水肿性疾病与其他利尿药合用,治疗充血性水肿、肝硬化腹水、肾性水肿等水肿性疾病,其目的在于纠正上述疾病时伴发的继发性醛固酮分泌增多,并对抗其他利尿药的排钾作用。也用于特发性水肿的治疗。
(2)高血压作为治疗高血压的辅助药物。
(3)原发性醛固酮增多症螺内酯可用于此病的诊断和治疗。
(4)低钾血症的预防与噻嗪类利尿药合用,增强利尿效应和预防低钾血症。
螺内酯片剂为已经上市的主要螺内酯制剂,需要经常检测其溶出度,现有溶出度的测定方法主要采用以0.1%十二烷基硫酸钠的0.1mol/L盐酸溶液1000ml为溶出介质评价体外溶出,溶出取样点为60min,限度为标示量的80%;此方法未考察不同取样点及其他pH的溶出介质中的体外溶出情况,不能完全反应自制药物与原研药物体外的溶出行为。
目前已经上市的螺内酯片由于处方及工艺上与原研制剂存在较大差别,可能达不到与原研药物一致的疗效。为此需要进行一致性评价,本发明为配合一致性评价,对已经上市的仿制药物制剂与原研药物制剂体外溶出行为是否一致提供一种检测方法,作为仿制药物与原研药物疗效一致的参考指标。
发明内容
本发明提供一种螺内酯片溶出度的检测方法,所述方法,步骤如下:步骤1,配制15L溶出介质,分别取螺内酯仿制片和原研片各12片,投入12杯的智能溶出仪中,设置方法:浆法75r/min,1000ml为溶出体积,取样点分别为10min、15min、20min、30min、45min、60min、90min、120min。
步骤2,分别于上述取样点取样进行螺内酯溶出量测定,比较两种片剂每个取样点的溶出量,计算f2因子。
其中,所述溶出介质,选自:pH4.5醋酸盐缓冲液+1.0%吐温80,pH6.8磷酸盐缓冲液+1.0%吐温80,水+1.0%吐温80三种。
用本发明的检测方法,可以真实的反映两种不同来源的螺内酯片的溶出度。
以下通过实验进一步说明本发明的方法和现有方法的区别:
从以上数据可知,本发明实施例1的方法在多项指标上优于现有技术。
作为溶出介质对自制制剂与参比制剂进行体外溶出测定,以评价自制制剂与参比制剂体外溶出是否一致。
国内上市的螺内酯片由于处方与原研药物差别较大,造成仅仅溶出度测定合格,但溶出曲线与原研药物差距较大,实施上述方案可淘汰掉与原研药物不一致的仿制药,并为新仿制的药物提供指标。
具体实施方式:
以下通过实施例进一步说明本发明。
实施例1
pH4.5醋酸盐缓冲液+1.0%吐温80介质的配制:称取吐温80 10g,取无水醋酸钠1.8g,加水1L,加入冰醋酸1.6ml,摇匀,超声使溶解,脱气,即得。
上述介质配制15L,分别取自制制剂和参比制剂12粒,投入12杯的智能溶出仪中,设置方法:浆法75r/min,1000ml为溶出体积,取样点分别为10min、15min、20min、30min、45min、60min、90min、120min。分别于上述取样点取样进行测定,比较自制制剂与参比制剂每个取样点的溶出量,计算f2因子。
结果如下:
10min | 15min | 20min | 30min | 45min | 60min | 90min | 120min | |
参比制剂 | 27 | 52 | 67 | 79 | 85 | 88 | 90 | 92 |
自制制剂 | 16 | 48 | 63 | 73 | 88 | 92 | 95 | 98 |
实施例2
pH6.8磷酸盐缓冲液+1.0%吐温80介质的配制:称取吐温80 10g,取磷酸二氢钾6.8g,取氢氧化钠0.9g,加水1L,摇匀,超声使溶解,脱气,即得。
上述介质配制15L,分别取自制制剂和参比制剂12粒,投入12杯的智能溶出仪中,设置方法:浆法75r/min,1000ml为溶出体积,取样点分别为10min、15min、20min、30min、45min、60min、90min、120min。分别于上述取样点取样进行测定,比较自制制剂与参比制剂每个取样点的溶出量,计算f2因子。
结果如下
10min | 15min | 20min | 30min | 45min | 60min | 90min | 120min | |
参比制剂 | 13 | 27 | 41 | 53 | 59 | 62 | 63 | 65 |
自制制剂 | 16 | 35 | 43 | 51 | 59 | 72 | 80 | 82 |
实施例3
水+1.0%吐温80介质的配制:称取吐温80 10g,加水1L,摇匀,超声使溶解,脱气,即得。
上述介质配制15L,分别取自制制剂和参比制剂12粒,投入12杯的智能溶出仪中,设置方法:浆法75r/min,1000ml为溶出体积,取样点分别为10min、15min、20min、30min、45min、60min、90min、120min。分别于上述取样点取样进行测定,比较自制制剂与参比制剂每个取样点的溶出量,计算f2因子。
结果如下:
10min | 15min | 20min | 30min | 45min | 60min | 90min | 120min | |
参比制剂 | 13 | 35 | 55 | 72 | 81 | 85 | 88 | 92 |
自制制剂 | 17 | 41 | 54 | 68 | 83 | 90 | 96 | 98 |
本发明溶出介质的筛选,筛选过程如下:
参照《仿制药质量与疗效一致性评价法规》及2015年版《中国药典》溶出介质的制备方法,除盐酸溶液外,其他pH的介质为规定中的pH4.5醋酸盐缓冲液,pH6.8磷酸盐缓冲液,和水。由于螺内酯为难溶性药物,几乎不溶于水,故在评价体外溶出的介质时,应加入适量的表面活性剂,由于十二烷基硫酸钠会与参比制剂中的辅料硫酸钙发生反应,故选择吐温80作为表面活性剂,筛选各介质下分别加入0.2%吐温80、0.5%吐温80、0.8%吐温80、1.0%吐温80时原料药的溶解情况,试验结果表明:上述介质加入1.0%吐温80时,溶解性较好,且根据《普通口服固体制剂溶出曲线测定与比较指导原则》,建议加入表面活性剂浓度推荐在0.01%-1.0%(W/V)范围,故筛选出表面活性剂浓度为1.0%。
筛选出以pH4.5醋酸盐缓冲液+1.0%吐温80、pH6.8磷酸盐缓冲液+1.0%吐温80、水+1.0%吐温80为溶出介质,对螺内酯片进行体外溶出进行指导和评价。经过溶出介质的筛选,筛选出以pH4.5醋酸盐缓冲液+1.0%吐温80、pH6.8磷酸盐缓冲液+1.0%吐温80、水+1.0%吐温80为溶出介质,对螺内酯片进行体外溶出进行指导和评价。
Claims (2)
1.一种螺内酯片剂溶出度的测定方法,所述方法,步骤如下:
步骤1,配制15L溶出介质,分别取螺内酯仿制片和原研片各12片,投入12杯的智能溶出仪中,设置方法:浆法75r/min,1000ml为溶出体积,取样点分别为10min、15min、20min、30min、45min、60min、90min、120min,
步骤2,分别于上述取样点取样进行螺内酯溶出量测定,比较两种片剂每个取样点的溶出量,计算f2因子。
2.根据权利要求1所述的方法,其中,所述溶出介质,选自:pH4.5醋酸盐缓冲液+1.0%吐温80,pH6.8磷酸盐缓冲液+1.0%吐温80,水+1.0%吐温80三种。
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CN111089821A (zh) * | 2018-10-23 | 2020-05-01 | 武汉武药科技有限公司 | 一种艾曲泊帕片的溶出度测定方法和应用 |
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