CN117838646A - 西吡氯铵含片及其制备方法 - Google Patents
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Abstract
本发明涉及一种西吡氯铵含片，该含片是由以下质量份组分组成：西吡氯铵固体分散体10～20份，制片辅料80～90份；其中，所述西吡氯铵固体分散体是由西吡氯铵与聚乙二醇(32)硬脂酸酯或硬脂酸聚氧乙烯(32)甘油酯或聚乙二醇(32)硬脂酸酯、硬脂酸聚氧乙烯(32)甘油酯二者任意比例混合物制备而成；本发明的有益效果是：制备的西吡氯铵含片在贮存过程中，含量不易下降，质量稳定；且在口腔内缓慢溶解，并能选择性地通过淋巴系统转动吸收而持续发挥药效，疗效好。
Description
技术领域
本发明涉及化学制药领域药物制剂的制备技术领域，具体涉及西吡氯铵含片及其制备方法。
背景技术
咽炎为咽部粘膜、粘膜下及淋巴组织的弥漫性炎症。病因可由病毒感染、细菌感染引起，病源体可直接感染咽部，也可由邻近组织感染，如鼻腔、鼻窦、甚至龋齿蔓延而来。理化因素刺激，包括烟酒过度、高温粉尘、有害气体等以及某些全身疾病，如贫血、便秘、下呼吸道慢性炎症、心血管疾病引起的淤血性改变均可致病。
口源性口臭，由多种原因引起的口腔微生物环境失调，如:牙龈炎、牙周炎、不良的口腔卫生等，促使菌斑量增加和滞留，厌氧菌、产臭的菌种及牙周致病菌数量、比例增加，造成的口腔异味。其中牙龈卟啉单胞菌、中间普雷沃菌、具核梭杆菌，被公认为是口源性口臭的主要菌。
西吡氯铵，化学名为氯化十六烷基吡啶一水合物，是一种阳离子表面活性剂，属于消毒防腐药。主要通过降低表面张力，增加细胞的通透性而抑制或杀灭细菌。能抑制炎症并可修复受损细胞，恢复正常细胞功能；可被口腔黏膜吸收、吸附，无刺激性，对牙面不着色，无明显毒副作用。对多种病原菌有抑制和杀灭作用，在国外被广泛用于口腔卫生保健。含片系指含于口腔中缓慢溶化产生局部或全身作用的片剂。根据西吡氯铵的理化特性及临床使用特点，将其制备成含片，方便使用、携带。西吡氯铵对口咽部细菌、胃肠道病原菌和真菌均有抑制或杀灭作用，对牙周主要致病菌也具有明显的抑制作用，能减少或抑制菌斑的形成，可作为临床辅助治疗和预防牙周病的有效抗菌剂，在国外已被广泛应用于口腔卫生保健。
由于西吡氯铵本身固有的物理性质熔点较低(80～84℃)，易挥发，因而其制剂在贮存过程中，含量容易下降，从而影响其疗效，通过考察市面上含西吡氯铵的各种产品的质量，发现都不同程度的存在含量下降的现象，鉴于西吡氯铵制剂的开发现状，研发一种质量稳定、疗效可靠的西吡氯铵制剂显得尤为重要。
发明内容
本发明的目的在于克服现有技术的不足，提供一种西吡氯铵含片及其制备方法，制备的西吡氯铵含片在贮存过程中，含量不易下降，质量稳定；且在口腔内缓慢溶解，并能选择性地通过淋巴系统转动吸收而持续发挥药效，疗效好。
鉴于现有的西吡氯铵制剂普遍存在含量下降的问题，有人通过制备西吡氯铵的γ-环糊精包合物来防止挥发性成分挥发，但由于西吡氯铵含片规格仅有0.2mg，包封过程很难控制包封率及包合物含量均匀度，从而制剂含量不可控，此方法很难有效实施。
本方案发明人研究发现聚乙二醇(32)硬脂酸酯和硬脂酸聚氧乙烯(32)甘油酯可作为西吡氯铵药物的固体分散体载体，制得的西吡氯铵含片在贮存过程中，含量不易下降，且能提高西吡氯铵的疗效。
本发明的目的是通过以下技术方案来实现的：
一种西吡氯铵含片，该含片是由以下质量份组分组成：西吡氯铵固体分散体10～20份，制片辅料80～90份；
其中，所述西吡氯铵固体分散体是由西吡氯铵与聚乙二醇(32)硬脂酸酯或硬脂酸聚氧乙烯(32)甘油酯或聚乙二醇(32)硬脂酸酯、硬脂酸聚氧乙烯(32)甘油酯二者任意比例混合物制备而成。
在本方案的一种优选实施例中，所述的西吡氯铵：聚乙二醇(32)硬脂酸酯或硬脂酸聚氧乙烯(32)甘油酯或二者任意比例混合物为10：1～100。
在本方案的一种优选实施例中，所述的制片辅料可以选自填充剂、粘合剂、矫味剂及其它药学上可接受的辅料中的至少一种。
在本方案的一种优选实施例中，所述的制片辅料各组分重量份为：填充剂77.5～87.5份；润滑剂0.5份；香精2份。
在本方案的一种优选实施例中，所述的填充剂选自甘露醇、木糖醇、乳糖、蔗糖中的一种或多种。
在本方案的一种优选实施例中，所述的润滑剂选自硬脂酸镁或亲水性润滑剂聚氧乙烯-8聚山嵛酸甘油酯。
优选的，所述的润滑剂为聚氧乙烯-8聚山嵛酸甘油酯。优选聚氧乙烯-8聚山嵛酸甘油酯，其抗摩擦效果优良，能有效提高压片过程传动比(压片中上下冲头作用力的比值)，对片剂硬度、崩解时限以及药物活性成分溶出均能产生有益影响。
在本方案的一种优选实施例中，所述的香精选自薄荷香精、橘子香精、柠檬香精中的一种或多种。
另一方面，本方案还提出一种用于制备上述西吡氯铵含片的方法，包括以下制备步骤：
S1、西吡氯铵固体分散体制备
先将聚乙二醇(32)硬脂酸酯或硬脂酸聚氧乙烯(32)或二者任意比例混合物加热熔化成液态，再加入西吡氯铵搅拌溶解形成均一透明溶液，冷却至室温，粉碎过60目以上筛，即得西吡氯铵固体分散体；
S2、西吡氯铵含片制备
将西吡氯铵固体分散体与填充剂、香精、润滑剂混合均匀直接压片即得。
在本方案的一种优选实施例中，所述的步骤S1中，是将聚乙二醇(32)硬脂酸酯或硬脂酸聚氧乙烯(32)或二者任意比例混合物的加热至60～70℃熔化成液态。
需说明的是：聚乙二醇(32)硬脂酸酯和硬脂酸聚氧乙烯(32)甘油酯作为固体分散体的载体，其能增加西吡氯铵的溶解度，有利于药物在消化过程中呈溶解状态，促进渗透性差的西吡氯铵在肠道中的吸收，并能促进药物与脂蛋白结合，促进淋巴吸收；同时，由于聚乙二醇(32)硬脂酸酯和硬脂酸聚氧乙烯(32)甘油酯能引起人体分泌胆汁和脂肪酶，使得本方案产品在禁食和进食状态的差异较小，从而减少食物的影响。
本发明的有益效果是：
本发明将西吡氯铵先与聚乙二醇(32)硬脂酸酯和硬脂酸聚氧乙烯(32)甘油酯的一种或任意比例的混合物制成固体分散体，再与辅料制片而成；本发明的西吡氯铵口含片在口腔内缓慢溶解，使药物较长时间停留在口腔及咽部，并能选择性地通过淋巴系统转动吸收而持续发挥药效，大大提高了西吡氯铵的疗效；按本发明制得的西吡氯铵含片经加速稳定性试验考察以及长期室温留样考察，制剂外观、崩解时限以及西吡氯铵含量均未有明显变化。
具体实施方式
下面进一步详细描述本发明的技术方案，但本发明的保护范围不局限于以下所述。
实施例
实施例1～6的配方如表2所示，且各实施例的固体分散体配方如表1所示。
表1西吡氯铵固体分散体制备，配比如下表，单位：g
制备方法：首先按表1配方比例将聚乙二醇(32)硬脂酸酯或硬脂酸聚氧乙烯(32)或二者任意比例混合物加热至60℃充分熔化成液态，再加入西吡氯铵充分搅拌溶解形成均一透明溶液，冷却至室温，粉碎过60目筛，分别制得固体分散体Ⅰ、固体分散体Ⅱ、固体分散体Ⅲ、固体分散体Ⅳ、固体分散体Ⅴ、固体分散体Ⅵ；然后按表2配比将每个实施例物料混合均匀，直接压片即得。
表2西吡氯铵含片制备，配比如下表，单位：g
实验例
本实验例均采取中试规模，制得样品符合用于加速稳定性试验样品生产规模要求，样品用于加速稳定性考察，考察本发明样品西吡氯铵含量是否会有明显变化。
制得样品进行了6个的加速稳定性试验，分别于0、1、2、3、6月取样；12月长期室温留样考察，分别于3、6、12取样，对西吡氯铵含片外观、崩解时限以及含量进行了考察，同时与0月初始数据进行对比。并与市售样品对比，其中对比例1样品由四川公司出售，批号220501，对比样品2由山东公司出售，批号220511，购于2022年11月，购买时样品已经生产了6个月，因此只做了长期6月与12月对比。可以看出下降幅度明显比实施例样品快。
表3考察结果
表3中结果表明，考察的各项指标均无明显变化，说明本发明很好地解决了西吡氯铵含片贮存中含量下降问题。
此外，需说明的是本方案发明人还采用了聚乙二醇4000和6000按本方案方法进行了对比实验，但在实验过程中发现聚乙二醇4000和6000均无法与西吡氯铵形成固体分散体。
以上所述仅是本发明的优选实施方式，应当理解本发明并非局限于本文所披露的形式，不应看作是对其他实施例的排除，而可用于各种其他组合、修改和环境，并能够在本文所述构想范围内，通过上述教导或相关领域的技术或知识进行改动。而本领域人员所进行的改动和变化不脱离本发明的精神和范围，则都应在本发明所附权利要求的保护范围内。
Claims (9)
1.一种西吡氯铵含片，其特征在于：
该含片是由以下质量份组分组成：西吡氯铵固体分散体10～20份，制片辅料80～90份；
其中，所述西吡氯铵固体分散体是由西吡氯铵与聚乙二醇(32)硬脂酸酯或硬脂酸聚氧乙烯(32)甘油酯或聚乙二醇(32)硬脂酸酯、硬脂酸聚氧乙烯(32)甘油酯二者任意比例混合物制备而成。
2.根据权利要求1所述的一种西吡氯铵含片，其特征在于，所述的西吡氯铵：聚乙二醇(32)硬脂酸酯或硬脂酸聚氧乙烯(32)甘油酯或二者任意比例混合物为10：1～100。
3.根据权利要求2所述的一种西吡氯铵含片，其特征在于，所述的制片辅料可以选自填充剂、粘合剂、矫味剂及其它药学上可接受的辅料中的至少一种。
4.根据权利要求3所述的一种西吡氯铵含片，其特征在于，所述的制片辅料各组分重量份为：
填充剂77.5～87.5份；
润滑剂0.5份；
香精2份。
5.根据权利要求4所述的一种西吡氯铵含片，其特征在于，所述的填充剂选自甘露醇、木糖醇、乳糖、蔗糖中的一种或多种。
6.根据权利要求4所述的一种西吡氯铵含片，其特征在于，所述的润滑剂选自硬脂酸镁或亲水性润滑剂聚氧乙烯-8聚山嵛酸甘油酯。
7.根据权利要求4所述的一种西吡氯铵含片，其特征在于，所述的香精选自薄荷香精、橘子香精、柠檬香精中的一种或多种。
8.一种用于制备权利要求1～7任一项所述西吡氯铵含片的方法，其特征在于，包括以下制备步骤：
S1、西吡氯铵固体分散体制备
先将聚乙二醇(32)硬脂酸酯或硬脂酸聚氧乙烯(32)或二者任意比例混合物加热熔化成液态，再加入西吡氯铵搅拌溶解形成均一透明溶液，冷却至室温，粉碎过60目以上筛，即得西吡氯铵固体分散体；
S2、西吡氯铵含片制备
将西吡氯铵固体分散体与填充剂、香精、润滑剂混合均匀直接压片即得。
9.根据权利要求8所述的制备方法，其特征在于：所述的步骤S1中，是将聚乙二醇(32)硬脂酸酯或硬脂酸聚氧乙烯(32)或二者任意比例混合物的加热至60～70℃熔化成液态。
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