CN116509823A - 酮咯酸氨丁三醇凝胶贴膏组合物、凝胶贴膏及其制备方法 - Google Patents
酮咯酸氨丁三醇凝胶贴膏组合物、凝胶贴膏及其制备方法 Download PDFInfo
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- CN116509823A CN116509823A CN202310485151.XA CN202310485151A CN116509823A CN 116509823 A CN116509823 A CN 116509823A CN 202310485151 A CN202310485151 A CN 202310485151A CN 116509823 A CN116509823 A CN 116509823A
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- ketorolac tromethamine
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- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims abstract description 20
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Abstract
本发明提供一种含有酮咯酸氨丁三醇的凝胶贴膏及其制备方法,所述酮咯酸凝胶贴膏组合物以质量份计包括如下组分:酮咯酸氨丁三醇0.1份‑10.0份、凝胶基质材料5.0份‑40.0份、保湿剂10.0份‑50.0份、透皮促渗剂0.1份‑10.0份、交联剂0.1份‑8.0份、抗氧剂0.01份‑3.0份、纯化水35.0份‑70.0份,所述抗氧剂选自二丁基羟基甲苯和亚硫酸钠;以用于解决酮咯酸氨丁三醇凝胶贴膏中有效成分氧化降解致使有关物质增加、含量降低、透皮效果差的问题。
Description
技术领域
本发明涉及药物制剂领域,具体涉及一种酮咯酸氨丁三醇凝胶贴膏组合物、酮咯酸氨丁三醇凝胶贴膏及其制备方法。
背景技术
酮咯酸氨丁三醇为酮咯酸的有机盐形式,是一种非甾体类的解热镇痛药物,并在体内可转化成酮咯酸,通过抑制前列腺素的合成发挥镇痛、抗炎的作用,可用于缓解多种中至重度急性疼痛及术后疼痛。近年来由于其强烈的镇痛作用及有效的炎症抑制作用备受关注,已经有片剂、注射剂、滴眼剂、鼻腔喷雾剂、凝胶剂等剂型上市。将酮咯酸氨丁三醇制备成外用制剂可以避免口服给药的胃肠道副作用,同时外用制剂使用方便、可减少给药次数并延长镇痛时间。
酮咯酸氨丁三醇外用制剂目前仅有凝胶剂上市,已有透皮贴剂和凝胶贴膏的报道,凝胶剂使用不便、容易与衣物接触并被擦除;透皮贴剂透气性较差且药物含量较低;另有专利CN112999199A公开了一种酮咯酸氨丁三醇凝胶贴膏,其中凝胶基质中使用甘油和其他多元醇作为保湿剂,而酮咯酸氨丁三醇的羧基易与甘油或多元醇的羟基成酯产生酯化杂质X,且该反应在室温下也易发生,该酯化杂质量随着凝胶贴膏放置时间的延长而逐渐增长。但甘油和多元醇物质是贴膏剂的优良保湿剂,暂无其他种类的保湿剂可取代,因此该酯化杂质的限度根据杂质毒理研究结果,以及结合欧美日对外用杂质限度的控制进行拓宽。但酮咯酸氨丁三醇还极易氧化,在凝胶贴膏的制备和储存过程易氧化降解产生杂质B,导致杂质B超限,最终导致药物中有效成分的含量降低。杂质B的氧化降解示意图如下所述。
另酮咯酸氨丁三醇易溶于水,对于水溶性药物来说,皮肤组织中的角质层是水溶性药物透皮吸收的一大障碍,因此提供一种稳定性和透皮效果均好的酮咯酸氨丁三醇凝胶贴膏是本领域亟待解决的技术问题。
发明内容
本发明的目的在于提供一种含有酮咯酸氨丁三醇的凝胶贴膏及其制备方法,以用于解决酮咯酸氨丁三醇凝胶贴膏中有效成分氧化降解致使有关物质增加、含量降低、透皮效果差的问题。
一方面,本发明提供了一种酮咯酸氨丁三醇凝胶贴膏组合物,所述酮咯酸凝胶贴膏组合物以质量份计包括如下组分:
所述抗氧剂选自二丁基羟基甲苯和亚硫酸钠。
在一些实施方式中,所述二丁基羟基甲苯和亚硫酸钠的质量比为15:1--1:1。
在一些实施方式中,所述凝胶基质材料包括聚丙烯酸部分中和物、聚丙烯酸及其盐、聚乙烯醇、阿拉伯胶、卡波姆任意一种或至少两种的组合;
优选地,所述凝胶基质材料包括聚丙烯酸钠部分中和物和/或聚乙烯醇。
在一些实施方式中,所述保湿剂包括甘油、丙二醇、聚乙二醇、果糖、山梨醇、木糖醇、尿素任意一种或至少两种的组合;
优选地,所述保湿剂包括甘油。
在一些实施方式中,所述交联剂包括甘羟铝、氢氧化铝三氯化铝、柠檬酸铝、合成硅酸铝、谷氨酸铝、硫酸铝钾、氢氧化钙、氯化钙任意一种或至少两种的组合;
优选地,所述交联剂为甘羟铝。
在一些实施方式中,所述透皮促渗剂选自L-薄荷醇、肉豆蔻酸异丙酯、克罗米通任意一种或至少两种的组合。
在一些实施方式中,所述凝胶贴膏组合还包括表面活性剂,所述表面活性剂的质量份≤3份,所述表面活性剂选自聚山梨酯类和/或司盘类。
在一些实施方式中,所述凝胶贴膏组合物还包括增黏剂,所述增黏剂的质量份≤25份,
优选地,所述增黏剂包括、丙烯酸接枝淀粉300、明胶、聚维酮、卡波姆、聚丙烯酸溶液、聚乙烯醇、明胶任意一种或至少两种的组合;
优选地,所述增黏剂包括丙烯酸接枝淀粉300、明胶、聚丙烯酸溶液任意一种或至少两种的组合。
在一些实施方式中,所述凝胶贴膏组合还包括pH调节剂,所述pH调节剂的质量份≤3份,
优选地,所述pH调节剂为有机酸和/或无机酸;
优选地,所述有机酸包括甲酸、乙酸、枸橼酸、酒石酸中的任意一种或至少两种的组合;
优选地,所述无机酸包括磷酸和/或盐酸;
优选地,所述pH调节剂包括L-酒石酸。
在一些实施方式中,所述凝胶贴膏组合还包括交联调节剂,所述交联调节剂的质量份≤3份,
优选地,所述交联调节剂包括酒石酸盐、柠檬酸盐、磷酸盐、苹果酸盐、依地酸盐、葡萄糖酸的盐中的任意一种或至少两种的组合,所述盐是钾盐、钠盐、钙盐中的任意一种或至少两种的组合;
优选地,所述交联调节剂为依地酸二钠。
在一些实施方式中,所述凝胶贴膏组合还包括填充剂,所述填充剂的质量份≤11份,
优选地,所述填充剂包括高岭土、二氧化钛、滑石粉、碳酸钙、氧化锌、膨润土、皂土、微粉硅胶、轻质无水硅酸等任意一种或至少两种的组合;
优选地,所述填充剂包括高岭土、二氧化钛。
在一些实施方式中,本发明更具体的提供了一种凝胶贴膏组合物以质量份计包括如下组分:
优选地,所述凝胶贴膏组合物以质量份计包括如下组分:
第二方面,本发明提供了一种制备酮咯酸氨丁三醇凝胶贴膏组合物的方法,包括以下步骤:
(1)将脂溶性抗氧剂和透皮促渗剂进行混合溶解后加入处方量的保湿剂中得到第一混合物,然后将第一混合物与凝胶基质材料进行第二混合,并搅拌拌均匀作为A相;
优选地,所述第一混合的物料还包括表面活性剂;所述第二混合的物料还包括交联剂、填充剂、交联调节剂、第一增黏剂中的任意一种或至少两种的组合;
(2)取水溶性抗氧剂加至纯化水中,搅拌使其溶解,作为B相;
优选地,加入的物料还包括pH调节剂和/或第二增黏剂;
(3)另取适量纯化水,加入酮咯酸氨丁三醇使其溶解,作为C相;
(4)将B相与A相混合均匀后缓慢加入C相,搅拌均匀得到均匀的凝胶贴
膏组合物;
优选地,搅拌均匀后可加入第三增黏剂继续搅拌直至得到均匀的凝胶贴膏组合物。
第三方面,本发明提供了一种酮咯酸氨丁三醇凝胶贴膏,所述酮咯酸氨丁三醇凝胶贴膏包括依次设置的背衬层、药物贮存层和保护层,所述药物贮存层的制备原料包括本发明第一方面提供的酮咯酸氨丁三醇凝胶贴膏组合物。
第四方面,本发明提供了一种所述酮咯酸氨丁三醇凝胶贴膏的方法,包括以无纺布作为背衬层,涂聚丙烯压纹膜作为保护层,将酮咯酸氨丁三醇凝胶贴膏组合物涂布于背衬层上得到形成含药凝胶层,在所述含药凝胶层上复合保护层得到所述酮咯酸氨丁三醇凝胶贴膏。
本发明具有以下优势:
1、本发明所述的酮咯酸氨丁三醇凝胶贴膏组合物通过加入二丁基羟基甲苯与亚硫酸钠的抗氧剂组合可以达到抑制酮咯酸氨丁三醇的的氧化降解的作用,降低了氧化杂质的含量;
2、本发明所述的酮咯酸氨丁三醇凝胶贴膏的有关物质含量得到了有效控制,经高温和加速稳定性考察,除杂质X外的总杂可控制在1%以内,氧化杂质B控制在0.5%以内,降低了产品稳定性的潜在风险(有关物质主要包括氧化杂质B以及酮咯酸氨丁三醇与甘油酯化形成的杂质X);
3、本发明所述的酮咯酸氨丁三醇凝胶贴膏具有较好的透皮效果,本发明意外发现通过表面活性剂与透皮促渗剂组合能够提高酮咯酸氨丁三醇的透皮效果,实现有效成分的快速和持续稳定释放。
附图说明
图1为试验例5所述的不同组别下大鼠对刺激的负反应数变化图。
具体实施方式
在下面的描述中阐述了很多具体细节以便于充分理解本发明。但是本发明能够以很多不同于在此描述的其它方式来实施,本领域技术人员可以在不违背本发明内涵的情况下做类似改进,因此本发明不受下面公开的具体实施的限制。
除非另有定义,本文所使用的所有的技术和科学术语与属于本发明的技术领域的技术人员通常理解的含义相同。在本发明的说明书中所使用的术语只是为了描述具体的实施例的目的,不是旨在于限制本发明。
本发明实施例1-5以及比较例1-7的酮咯酸氨丁三醇凝胶贴膏按照以下方法制备
(1)将处方量脂溶性抗氧剂、透皮促渗剂、表面活性剂进行混合溶解后加入处方量的保湿剂中得到第一混合物,然后将第一混合物与处方量凝胶基质材料、交联剂、填充剂、交联调节剂、第一增黏剂进行第二混合,并搅拌拌均匀作为A相;
(2)取处方量水溶性抗氧剂、pH调节剂、第二增黏剂加至纯化水中,搅拌使其溶解,作为B相;
(3)另取处方量纯化水,加入处方量酮咯酸氨丁三醇使其溶解,作为C相;
(4)将B相与A相混合均匀后缓慢加入C相,搅拌均匀后可加入第三增黏剂继续搅拌直至得到均匀的凝胶贴膏组合物得到均匀的凝胶贴膏组合物;
(5)以无纺布作为背衬层,聚丙烯压纹膜为防粘层,将以上贴膏组合物进行涂布、裁切、包装等工序,得酮咯酸氨丁三醇凝胶贴膏。
表1实施例1-5处方配比
表2对比例1-7的处方配比
实施例1-4的处方考察了二丁基羟基甲苯与亚硫酸钠的不同配比,实施例5处方不使用抗氧剂,比较例1-7与实施例1相比,使用了不同抗氧剂的组合。
本发明实施例6以及比较例8-13的酮咯酸氨丁三醇凝胶贴膏按照以下方法制备
(1)将处方量脂溶性抗氧剂、透皮促渗剂、表面活性剂进行混合溶解后加入处方量的保湿剂中得到第一混合物,然后将第一混合物与处方量凝胶基质材料、交联剂、填充剂、交联调节剂、第一增黏剂进行第二混合,并搅拌拌均匀作为A相;
(2)取处方量水溶性抗氧剂、pH调节剂、第二增黏剂加至纯化水中,搅拌使其溶解,作为B相;
(3)另取处方量纯化水,加入处方量酮咯酸氨丁三醇使其溶解,作为C相;
(4)将B相与A相混合均匀后缓慢加入C相,搅拌均匀后可加入第三增黏剂继续搅拌直至得到均匀的凝胶贴膏组合物得到均匀的凝胶贴膏组合物;
(5)以无纺布作为背衬层,聚丙烯压纹膜为防粘层,将以上贴膏组合物进行涂布、裁切、包装等工序,得酮咯酸氨丁三醇凝胶贴膏。
表3实施例6及比较例8-13处方配比
与实施例6相比,比较例8-13的处方中部分不使用表面活性剂(比较例8),部分将透皮促渗剂克罗米通、肉豆蔻酸异丙酯替换为丙二醇(比较例9)、二乙二醇单乙醚(比较例10)、DMSO(比较例11)、聚甘油油酸酯(比较例12),只使用L-薄荷醇作为透皮促渗剂(比较例13)。
比较例14
按照专利CN112999199A实施例1所公开的处方表和制备方法制备酮咯酸氨丁三醇凝胶贴膏。
制备工艺:将处方量的聚丙烯酸钠、二羟基氨基乙酸铝、EDTA-2Na、对羟基苯甲酸甲酯、肉豆蔻酸异丙酯、高岭土混匀,加入处方量的甘油,搅拌均匀,放至室温作为A相。取处方量的酒石酸及羧甲基纤维素钠加至纯化水中,搅拌使其溶解,作为B相。另取适量纯化水,加入处方量的酮咯酸氨丁三醇使其溶解,作为C相。将B相与C相混合均匀后缓慢加至A相中,继续搅拌直至得到均匀的含药凝胶基质。以无纺布作为背衬层,涂二甲基硅油的PET聚酯膜作为防粘层,将以上基质进行涂布、裁切、包装等工序,得酮咯酸氨丁三醇凝胶贴膏。
表4比较例14处方配比
分类 | 组分 | 处方占比(mg/g) |
活性成分 | 酮咯酸氨丁三醇 | 25 |
凝胶基质 | 聚丙烯酸钠 | 30 |
凝胶基质 | 羧甲基纤维素钠 | 40 |
保湿剂 | 甘油 | 300 |
透皮促进剂 | 肉豆蔻酸异丙酯 | 5 |
防腐剂 | 对羟基苯甲酸甲酯 | 5 |
填充剂 | 高岭土 | 10 |
pH调节剂 | 酒石酸 | 2 |
交联剂 | 甘羟铝 | 2 |
交联调节剂 | EDTA-2Na | 1 |
N/A | 纯化水 | 580 |
试验例1粘着力和赋形性试验
粘着力:按中国药典2020年版第一部贴膏项下方法进行测试:取测试样品3片在室温下除去盖衬,置于长30cm、与水平面成30°的斜面中央,膏面向上,斜面上部10cm及下部15cm用0.025mm厚的涤纶薄膜覆盖,中央留出5cm膏面,用21号钢球自斜面顶端自由滚下。
赋形性:按中国药典2020年版第一部贴膏项下方法进行检查,取测试样品1片,置37℃恒温箱中,取出,用夹子将测试样品固定在一平整不朽钢板上,钢板与水平面的倾斜角为60°,放置24h,膏面无流淌现象。
对实施例1-6以及比较例1-14制备的凝胶贴膏按上述方法进行粘着力和赋型性考察,结果表明各实施例和比较例的成型性、粘着力均符合药典要求。
试验例2高温稳定性试验
选取实施例1-5及比较例1-7、比较例14进行影响因素考察,用高效液相色谱法测定考察后的各样品在高温50℃条件下,氧化杂质B的变化情况。
其中液相色谱主要条件如下所示:
流动相:0.05mol/L磷酸二氢铵溶液(用磷酸调节pH值至3.0)-四氢呋喃(70:30)
色谱柱:ZORBOX SB-C18,4.6*250mm,5μm
流速:1.0ml/min
柱温:40℃
波长:313nm
具体实验结果如下:
表5有关物质数据统计表
上述结果表明,本发明提供的酮咯酸氨丁三醇凝胶贴膏在加入抗氧剂后,氧化杂质B在50℃高温条件下其增长速度明显减慢,通过对比实施例1与比较例,可知在使用量相同的情况下使用二丁基羟基甲苯与亚硫酸钠抗氧剂组合的实施例1杂质B的增长速率最慢,而使用不同用量的二丁基羟基甲苯与亚硫酸钠组合,随着二丁基羟基甲苯和亚硫酸钠质量比为10:1时,在50℃条件下放置30天氧化杂质B的基本不增加。
试验例3体外释放实验
按照中国药典2010版第二部附录XD中释放度测定法中第三法(桨碟法,用于透皮贴剂)中提供的方法对实施例6及比较例8-13得到的凝胶贴膏紧急释放度测定。具体方法如下
试验以生理盐水为释放介质,将释放介质加入溶出杯内,预温至(32±0.5℃)将凝胶贴膏除去盖衬层,裁剪成2.5cm×7.5cm大小,平放入透析袋(截留分子量14,000)中,释放面朝上,置于两层碟片之间,使碟片边缘夹住透析袋两端,再用皮筋缠绕固定,以固定碟片。于10min、20min、30min、45min、60min、90min、2h、2.5h、3h和4h分别从溶出杯内取样6mL,并补充等体积(32+0.5)℃新鲜释放介质,平行试验6片,取平均值计算。经过检测表明,本申请实施例中的凝胶贴膏的体外释放度均在2h达到90%以上。
试验例4体外透皮实验
采用改良Franz扩散池法,以猪腹部皮肤为屏障,用实施例6及比较例8-14制备得到的巴布贴剂进行进行体外透皮试验。具体实验方法为:
将洗净的猪皮肤分别固定于Franz扩散池的释放口,接受室中加入pH7.4磷酸缓冲液作释放介质,保持内皮层与溶液密切接触。将揭去盖衬层的凝胶贴膏贴于皮肤上,调节水浴使外层套层温度恒定于(32±0.5)℃,搅拌速度为600rpm,分别于0、1h、2h、4h、6h、8h、12h、24h小时吸取释放介质4ml,同时补加等量PBS液。计算累计吸收百分数(即累计透过的酮咯酸氨丁三醇占药物储库中酮咯酸氨丁三醇总量的百分比分数)结果如下表:
表6体外透皮实验数据
上述结果表明,本发明提供酮咯酸氨丁三醇凝胶贴膏,在进行体外透皮吸收实验时,各组合的药物释放率随时间增加速度较为均匀,而使用表面活性剂和克罗米通、肉豆阔酸异丙酯以及L-薄荷醇作为透皮促渗剂的实施例6,其累计透过率仅次于使用DMSO作为透皮促渗剂的比较例11,但DMSO的毒性较强,因此不使用其作为透皮促渗剂。
试验例5药效学试验
(1)实验动物处理取雄性昆明种大鼠固定于鼠板上,用电剪剃除腹部鼠毛,在腹部皮肤上固定一直径为2cm的圆周。将电极置于中心,另一电极于圆周的每个十等分点变动。调整生理刺激仪的输出电压,刺激持续时间为1秒。当输出电压为0时,刺激10次有连续5次发出嘶鸣声和输出电压为72V时,刺激10次有连续5次不叫者弃去。筛选出合格的大鼠,备用。
取大鼠固定于鼠板上,用电动剃刀剃掉背部正中皮肤的鼠毛,约10cm2大小区域,使皮肤裸露。剃毛后将大鼠放置休息24h,使其背部皮肤恢复至自然状态。
(2)实验组别分类①空白对照组(不进行处理);②空白基质对照组;③酮咯酸氨丁三醇凝胶贴膏组(实施例6制备得到);④酮咯酸氨丁三醇凝胶贴膏组(对比例14制备得到)。
(3)给药方案及评价取40只雄性昆明大鼠,随机分为4组,每组10只。随后,在裸露区的皮肤贴敷上凝胶贴膏,面积约为4cm2;或以肌肉注射形式给予酮咯酸氨丁三醇。用针刺测试用药部分皮肤区域周边宽约6mm的带状区的痛觉反应,痛觉尚存在时,刺激处的皮肤有收缩现象。每次每只大鼠在带状区的不同点总共刺激10次,记录每只大鼠对刺激的负反应数(即针刺后大鼠背部皮肤无收缩现象)。给药后分别于0.5、1、2、3、4、6、8、10、12、24h测试一次。结果如图1所示,实施例6所制备的贴膏与实施例14相比,药效稍快,且持续时间更长,以上结果说明,透皮促渗剂与表面活性剂的组合能够提高酮咯酸氨丁三醇的透皮效果,实现有效成分的快速和持续稳定释放。
Claims (10)
1.一种酮咯酸氨丁三醇凝胶贴膏组合物,其特征在于,所述酮咯酸凝胶贴膏组合物以质量份计包括如下组分:
所述抗氧剂选自二丁基羟基甲苯和亚硫酸钠。
2.根据权利要求1所述的一种酮咯酸氨丁三醇凝胶贴膏组合物,其特征在于,所述二丁基羟基甲苯和亚硫酸钠的质量比为15:1--1:1。
3.根据权利要求1所述的一种酮咯酸氨丁三醇凝胶贴膏组合物,其特征在于,所述凝胶基质材料包括聚丙烯酸部分中和物、聚丙烯酸及其盐、聚乙烯醇、阿拉伯胶、卡波姆任意一种或至少两种的组合;
优选地,所述凝胶基质材料包括聚丙烯酸钠部分中和物和/或聚乙烯醇;
所述保湿剂包括甘油、丙二醇、聚乙二醇、果糖、山梨醇、木糖醇、尿素任意一种或至少两种的组合;
优选地,所述保湿剂包括甘油;
优选地,所述交联剂包括甘羟铝、氢氧化铝三氯化铝、柠檬酸铝、合成硅酸铝、谷氨酸铝、硫酸铝钾、氢氧化钙、氯化钙任意一种或至少两种的组合;
优选地,所述交联剂为甘羟铝。
4.根据权利要求1所述的一种酮咯酸氨丁三醇凝胶贴膏组合物,其特征在于,所述透皮促渗剂选自L-薄荷醇、肉豆蔻酸异丙酯、克罗米通任意一种或至少两种的组合。
5.根据权利要求4所述的一种酮咯酸氨丁三醇凝胶贴膏组合物,其特征在于,所述凝胶贴膏组合还包括表面活性剂,所述表面活性剂的质量份≤3份,所述表面活性剂选自聚山梨酯类和/或司盘类。
6.根据权利要求1所述的一种酮咯酸氨丁三醇凝胶贴膏组合物,其特征在于,所述凝胶贴膏组合物还包括增黏剂,所述增黏剂的质量份≤25份,
优选地,所述增黏剂包括、丙烯酸接枝淀粉300、明胶、聚维酮、卡波姆、聚丙烯酸溶液、聚乙烯醇、明胶任意一种或至少两种的组合;
优选地,所述增黏剂包括丙烯酸接枝淀粉300、明胶、聚丙烯酸溶液任意一种或至少两种的组合;
优选地,所述凝胶贴膏组合还包括pH调节剂,所述pH调节剂的质量份≤3份,优选地,所述pH调节剂为有机酸和/或无机酸;
优选地,所述有机酸包括甲酸、乙酸、枸橼酸、酒石酸中的任意一种或至少两种的组合;
优选地,所述无机酸包括磷酸和/或盐酸;
优选地,所述pH调节剂包括L-酒石酸;
优选地,所述凝胶贴膏组合还包括交联调节剂,所述交联调节剂的质量份≤3份,优选地,所述交联调节剂包括酒石酸盐、柠檬酸盐、磷酸盐、苹果酸盐、依地酸盐、葡萄糖酸的盐中的任意一种或至少两种的组合,所述盐是钾盐、钠盐、钙盐中的任意一种或至少两种的组合;
优选地,所述交联调节剂为依地酸二钠;
优选地,所述凝胶贴膏组合还包括填充剂,所述填充剂的质量份≤11份,
优选地,所述填充剂包括高岭土、二氧化钛、滑石粉、碳酸钙、氧化锌、膨润土、皂土、微粉硅胶、轻质无水硅酸等任意一种或至少两种的组合;
优选地,所述填充剂包括高岭土、二氧化钛。
7.根据权利要求1-6任一项所述的一种酮咯酸氨丁三醇凝胶贴膏组合物,其特征在于,所述凝胶贴膏组合物以质量份计包括如下组分:
优选地,所述凝胶贴膏组合物以质量份计包括如下组分:
8.一种制备权利要求1-7任一项所述酮咯酸氨丁三醇凝胶贴膏组合物的方法,其特征在于,包括以下步骤:
(1)将脂溶性抗氧剂和透皮促渗剂进行混合溶解后加入处方量的保湿剂中得到第一混合物,然后将第一混合物与凝胶基质材料进行第二混合,并搅拌拌均匀作为A相;
优选地,所述第一混合的物料还包括表面活性剂;所述第二混合的物料还包括交联剂、填充剂、交联调节剂、第一增黏剂中的任意一种或至少两种的组合;
(2)取水溶性抗氧剂加至纯化水中,搅拌使其溶解,作为B相;
优选地,加入的物料还包括pH调节剂和/或第二增黏剂;
(3)另取适量纯化水,加入酮咯酸氨丁三醇使其溶解,作为C相;
(4)将B相与A相混合均匀后缓慢加入C相,搅拌均匀得到均匀的凝胶贴膏组合物;
优选地,搅拌均匀后可加入第三增黏剂继续搅拌直至得到均匀的凝胶贴膏组合物。
9.一种酮咯酸氨丁三醇凝胶贴膏,其特征在于,所述酮咯酸氨丁三醇凝胶贴膏包括依次设置的背衬层、药物贮存层和保护层,所述药物贮存层的制备原料包括如权利要求1-7任一项所述的酮咯酸氨丁三醇凝胶贴膏组合物。
10.一种制备权利要求9任一项所述酮咯酸氨丁三醇凝胶贴膏的方法,其特征在于,以无纺布作为背衬层,涂聚丙烯压纹膜作为保护层,将酮咯酸氨丁三醇凝胶贴膏组合物涂布于背衬层上得到形成含药凝胶层,在所述含药凝胶层上复合保护层得到所述酮咯酸氨丁三醇凝胶贴膏。
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CN113242734A (zh) * | 2018-11-26 | 2021-08-10 | 艾葳生物科技有限公司 | 用于药物递送的药用生物可溶凝胶 |
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