CN116211868B - 一种头孢克肟抗生素片剂及其制备方法 - Google Patents
一种头孢克肟抗生素片剂及其制备方法 Download PDFInfo
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
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- A—HUMAN NECESSITIES
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
Abstract
本发明属于药物制剂技术领域，具体涉及一种头孢克肟抗生素片剂及其制备方法。本发明利用脂质体技术对头孢克肟进行包裹，通过优选脂质载体材料，尤其是加入了岩藻甾醇、三乙醇胺与磷脂酰乙醇胺形成封闭的脂质囊泡，提高了头孢克肟脂质体的载药量和包封率，同时也提高了头孢克肟片对强光和高温的稳定性。
Description
技术领域
本发明属于药物制剂技术领域，具体涉及一种头孢克肟抗生素片剂及其制备方法。
背景技术
呼吸道感染是最常见的呼吸系统的疾病之一，是由多种微生物包括细菌、病毒、支原体、真菌、寄生虫等引起的感染性疾病。根据其部位分为上呼吸道感染和下呼吸道感染，前者包括鼻炎、咽炎和喉炎；后者包括气管炎、支气管炎和肺炎。治疗时可以选择相应、有效的抗生素来杀灭细菌。
头孢克肟为口服用的第三代头孢菌素类抗生素，适用于治疗敏感菌所致的呼吸系统感染，如支气管炎、肺炎等。
中国专利CN101966159A、CN101966166A、CN101972231A、CN101966160A、CN101966154A分别公开了含头孢克肟脂质体的片剂、胶囊剂、干混悬剂、分散片、颗粒剂，根据说明书中实施例记载的头孢克肟脂质体配方，其脂质载体成分用量较大，会导致头孢克肟脂质体载药量低，制成制剂的难度很高，容易引起制剂质量不合格等问题。
中国专利CN102327235A公开了一种头孢克肟脂质纳米粒固体制剂及其制法，以头孢克肟和硬脂酸、月桂酸溶入有机溶剂构成油相，以吐温80和氢化蓖麻油聚氧乙烯醚40的水溶液为水相，采用搅拌乳化和高压乳匀相结合的方法，将头孢克肟包载于固体脂质纳米粒中制得头孢克肟固体脂质纳米粒制剂，根据说明书的记载，其头孢克肟脂质体的载药量高达90％，显然不符合实际药学常理。
发明内容
本发明克服现有技术的不足，提供了一种高稳定性的头孢克肟抗生素片剂，解决了头孢克肟对于高温、强光不稳定的问题。
具体而言，本发明的技术方案如下：
本发明提供了一种头孢克肟片，所述头孢克肟片由头孢克肟脂质体、填充剂、崩解剂、润滑剂、矫味剂组成。
所述头孢克肟脂质体的制备方法为：
将1-4重量份磷脂酰乙醇胺、0.5-2重量份的岩藻甾醇溶于有机溶剂，冷冻干燥得到冻干粉末，用溶有1重量份头孢克肟、0.1-0.6重量份三乙醇胺的水溶液水化，超声，过滤，浓缩，得到头孢克肟脂质体。
三乙醇胺，无色油状液体，溶于水中为头孢克肟提供一个稳定的环境，同时在水化脂质载体膜时，能够迅速结合磷脂酰乙醇胺和岩藻甾醇形成封闭的脂质囊泡，有利于头孢克肟的包封。
在实施例中，所述有机溶剂选自正丁醇、三氯甲烷、异丙醇中的一种。
在其中一个较优的实施例中，所述有机溶剂为正丁醇。
在其中一个较优的实施例中，所述磷脂酰乙醇胺的用量为2重量份，所述岩藻甾醇的用量为1重量份，所述三乙醇胺的用量为0.3重量份。
所述的头孢克肟片中填充剂的主要作用为增加质量和体积，改善压缩成形性，提高头孢克肟片的含量均匀度，可选用任何常规的填充剂，例如淀粉、预胶化淀粉、糊精、蔗糖、乳糖、微晶纤维素、甘露醇等。
在其中一个较优的实施例中，所述填充剂为淀粉和糊精。
所述崩解剂选用亲水性、具有良好吸水膨胀性的物质，能够瓦解片剂的结合力，使头孢克肟片崩解，有利于头孢克肟的溶解和吸收，可选用任何常规的崩解剂，例如，干淀粉、羧甲淀粉钠、低取代羟丙纤维素、交联羧甲基纤维素钠、交联聚维酮等。
在其中一个较优的实施例中，所述崩解剂为低取代羟丙纤维素。
所述润滑剂起到降低颗粒之间摩擦力、改善粉体流动性的作用，保证压片的顺利进行，可选用任何常规的润滑剂，例如硬脂酸镁、滑石粉、微粉硅胶、聚乙二醇等。
在其中一个较优的实施例中，所述润滑剂为微粉硅胶。
所述矫味剂可选用任何常规的矫味剂，主要是改善头孢克肟的特殊臭味，改善口感，例如，甘露醇、蔗糖、三氯蔗糖、阿司帕坦、赤藓糖醇、木糖醇等。
在其中一个较优的实施例中，所述矫味剂为阿司帕坦。
需要说明的是，上述填充剂、崩解剂、润滑剂、矫味剂等辅料可根据具体配方选择的具体的辅料，具体的辅料可以根据常规用量进行添加，例如，低取代羟丙纤维素的用量为总配方量的2-5％，羧甲淀粉钠的用量为1-6％，硬脂酸镁的用量为0.1-1％，滑石粉的用量为0.1-3％，微粉硅胶的用量为0.1-0.3％，等等，也可根据具体工艺中的物料状态进行各辅料用量的适当调整。
进一步的，所述头孢克肟片还可进行包衣，可选用任何合适的包衣材料对头孢克肟素片进行包衣，包衣增重可按照材料类型进行常规选择。
本发明上述头孢克肟片，均通过中国药典2020版四部通则0101片剂项下的各项规定，各项检查均合格。
与现有技术相比，本发明的有益效果在于：
本发明提供的头孢克肟片利用脂质体技术对主药进行包裹，通过优选脂质载体材料，尤其是加入了岩藻甾醇、三乙醇胺与磷脂酰乙醇胺形成封闭的脂质囊泡，提高了头孢克肟脂质体的载药量和包封率，进一步提高了头孢克肟片对强光和高温的稳定性。
附图说明
图1：实施例1-5、对比实施例1-5头孢克肟片光照稳定性试验有关物质总含量变化
图2：实施例1-5、对比实施例1-5头孢克肟片高温稳定性试验有关物质总含量变化
具体实施方式
为了使本发明的目的、技术方案更加清楚明白，以下结合实施例，对本发明做进一步的说明，但是本发明的保护范围并不限于这些实施例，实施例仅用于解释本发明。本领域技术人员应该理解的是，凡是不背离本发明构思的改变或等同替代均包括在本发明的保护范围之内。
实施例1头孢克肟片(100片)
将2重量份磷脂酰乙醇胺、1重量份的岩藻甾醇溶于适量正丁醇，冷冻干燥(冷冻至-10℃，真空干燥)得到冻干粉末，再用溶有1重量份头孢克肟、0.3重量份三乙醇胺的水溶液水化冻干粉末，超声10min，微滤，浓缩至适当密度，得到头孢克肟脂质体。
取含有10g头孢克肟的头孢克肟脂质体，加入适量填充剂(淀粉、糊精)，湿法制粒，干燥，整粒，加入占总质量为3.5％的低取代羟丙纤维素、占总质量为0.2％的微粉硅胶，加入占总质量为0.08％的阿司帕坦，混合，压片，制成头孢克肟片，规格为0.1g。
实施例2头孢克肟片(100片)
将1重量份磷脂酰乙醇胺、0.5重量份的岩藻甾醇溶于适量三氯甲烷，冷冻干燥(冷冻至-10℃，真空干燥)得到冻干粉末，再用溶有1重量份头孢克肟、0.1重量份三乙醇胺的水溶液水化冻干粉末，超声10min，微滤，浓缩至适当密度，得到头孢克肟脂质体。
取含有10g头孢克肟的头孢克肟脂质体，加入适量填充剂(淀粉、乳糖)，湿法制粒，干燥，整粒，加入占总质量为4％的羧甲淀粉钠、占总质量为0.5％的硬脂酸镁，加入占总质量为0.05％的三氯蔗糖，混合，压片，制成头孢克肟片，规格为0.1g。
实施例3头孢克肟片(100片)
将4重量份磷脂酰乙醇胺、2重量份的岩藻甾醇溶于适量异丙醇，冷冻干燥(冷冻至-10℃，真空干燥)得到冻干粉末，再用溶有1重量份头孢克肟、0.6重量份三乙醇胺的水溶液水化冻干粉末，超声10min，微滤，浓缩至适当密度，得到头孢克肟脂质体。
取含有10g头孢克肟的头孢克肟脂质体，加入适量填充剂(微晶纤维素、甘露醇)，湿法制粒，干燥，整粒，加入占总质量为2.5％的交联羧甲基纤维素钠、占总质量为1％的滑石粉，加入占总质量为0.2％的蔗糖，混合，压片，制成头孢克肟片，规格为0.1g。
实施例4头孢克肟片(100片)
将3重量份磷脂酰乙醇胺、1.5重量份的岩藻甾醇溶于适量正丁醇，冷冻干燥(冷冻至-10℃，真空干燥)得到冻干粉末，再用溶有1重量份头孢克肟、0.4重量份三乙醇胺的水溶液水化冻干粉末，超声10min，微滤，浓缩至适当密度，得到头孢克肟脂质体。
取含有10g头孢克肟的头孢克肟脂质体，加入适量填充剂(淀粉、蔗糖)，湿法制粒，干燥，整粒，加入占总质量为3％的交联聚维酮、占总质量为0.4％的聚乙二醇4000，加入占总质量为0.2％的甘露醇，混合，压片，制成头孢克肟片，规格为0.1g。
实施例5头孢克肟片(100片)
将2重量份磷脂酰乙醇胺、1重量份的岩藻甾醇溶于适量正丁醇，冷冻干燥(冷冻至-10℃，真空干燥)得到冻干粉末，再用溶有1重量份头孢克肟、0.3重量份三乙醇胺的水溶液水化冻干粉末，超声10min，微滤，浓缩至适当密度，得到头孢克肟脂质体。
取含有10g头孢克肟的头孢克肟脂质体，加入适量填充剂(淀粉、糊精)，湿法制粒，干燥，整粒，加入占总质量为3.5％的低取代羟丙纤维素、占总质量为0.2％的微粉硅胶，加入占总质量为0.08％的阿司帕坦，混合，压片，制成头孢克肟片，薄膜包衣，增重2.5％，规格为0.1g。
对比实施例1头孢克肟片(100片)
将2重量份磷脂酰乙醇胺、1重量份的胆固醇溶于适量正丁醇，冷冻干燥(冷冻至-10℃，真空干燥)得到冻干粉末，再用溶有1重量份头孢克肟、0.3重量份三乙醇胺的水溶液水化冻干粉末，超声10min，微滤，浓缩至适当密度，得到头孢克肟脂质体。
取含有10g头孢克肟的头孢克肟脂质体，加入适量填充剂(淀粉、糊精)，湿法制粒，干燥，整粒，加入占总质量为3.5％的低取代羟丙纤维素、占总质量为0.2％的微粉硅胶，加入占总质量为0.08％的阿司帕坦，混合，压片，制成头孢克肟片，规格为0.1g。
对比实施例2头孢克肟片(100片)
将2重量份磷脂酰乙醇胺、1重量份的岩藻甾醇溶于适量正丁醇，冷冻干燥(冷冻至-10℃，真空干燥)得到冻干粉末，再用溶有1重量份头孢克肟的水溶液水化冻干粉末，超声10min，微滤，浓缩至适当密度，得到头孢克肟脂质体。
取含有10g头孢克肟的头孢克肟脂质体，加入适量填充剂(淀粉、糊精)，湿法制粒，干燥，整粒，加入占总质量为3.5％的低取代羟丙纤维素、占总质量为0.2％的微粉硅胶，加入占总质量为0.08％的阿司帕坦，混合，压片，制成头孢克肟片，规格为0.1g。
对比实施例3头孢克肟片(100片)
将5重量份磷脂酰乙醇胺、0.5重量份的岩藻甾醇溶于适量正丁醇，冷冻干燥(冷冻至-10℃，真空干燥)得到冻干粉末，再用溶有1重量份头孢克肟、0.8重量份三乙醇胺的水溶液水化冻干粉末，超声10min，微滤，浓缩至适当密度，得到头孢克肟脂质体。
取含有10g头孢克肟的头孢克肟脂质体，加入适量填充剂(淀粉、糊精)，湿法制粒，干燥，整粒，加入占总质量为3.5％的低取代羟丙纤维素、占总质量为0.2％的微粉硅胶，加入占总质量为0.08％的阿司帕坦，混合，压片，制成头孢克肟片，规格为0.1g。
对比实施例4头孢克肟片(100片)
将1重量份头孢克肟、2重量份磷脂酰乙醇胺、1重量份的岩藻甾醇溶于适量正丁醇，冷冻干燥(冷冻至-10℃，真空干燥)得到冻干粉末，再用溶有0.3重量份三乙醇胺的水溶液水化冻干粉末，超声10min，微滤，浓缩至适当密度，得到头孢克肟脂质体。
取含有10g头孢克肟的头孢克肟脂质体，加入适量填充剂(淀粉、糊精)，湿法制粒，干燥，整粒，加入占总质量为3.5％的低取代羟丙纤维素、占总质量为0.2％的微粉硅胶，加入占总质量为0.08％的阿司帕坦，混合，压片，制成头孢克肟片，规格为0.1g。
对比实施例5头孢克肟片(国药准字H20061245)
验证实施例
一、头孢克肟脂质体的载药量与包封率评价
载药量和包封率是脂质体质量评价的重要指标。载药量指脂质体中所含药物的质量百分比；包封率是指包入脂质体的药物量占体系总药量的百分比。
表1头孢克肟脂质体的载药量与包封率
表1为本发明实施例头孢克肟脂质体的载药量和包封率评价，根据结果显示，磷脂种类、固醇类物质种类、三乙醇胺的加入，以及其用量比例都对头孢克肟脂质体的质量有较大影响。载药量的高低直接影响到药物的临床应用剂量，载药量愈大，愈易满足临床需要，但是载药量越高，较高的膜扩散性往往容易导致药物渗漏，所以同时具有高载药量和高包封率的脂质体是十分困难的。
二、头孢克肟片的稳定性评价
1.光照稳定性试验
将实施例1-5头孢克肟片、对比实施例1-5头孢克肟片作为供试品，放在装有日光灯的光照箱中，于照度为4500lx±500lx的条件下放置20天，分别于第0天、第5天、第10天、第20天取样，检测头孢克肟有关物质总含量的变化。
头孢克肟有关物质照高效液相色谱法(通则0512)测定。供试品溶液：取本品适量，加磷酸盐缓冲液(pH7.0)溶解并稀释制成每1ml中约含1mg的溶液。对照溶液：精密量取供试品溶液适量，用磷酸盐缓冲液(pH 7.0)定量稀释制成每1ml中约含0.01mg的溶液。系统适用性溶液取头孢克肟对照品适量，加水溶解并稀释制成每1ml中约含1mg的溶液，于沸水浴上加热45分钟，冷却。色谱条件：用十八烷基硅烷键合硅胶为填充剂；以四丁基氢氧化铵溶液(取10％四丁基氢氧化铵溶液25ml，加水1000ml，摇匀，用1.5mol/L磷酸溶液调节pH值至7.0)-乙腈(72∶28)为流动相；检测波长为254nm；柱温为40℃；进样体积20μl。系统适用性要求：系统适用性溶液色谱图中，按头孢克肟(E)异构体、头孢克肟的顺序出峰，头孢克肟(E)异构体峰与头孢克肟峰之间的分离度应符合要求。测定法：精密量取供试品溶液与对照溶液，分别注入液相色谱仪，记录色谱图至主成分峰保留时间的2.5倍。限度：供试品溶液色谱图中如有杂质峰，单个杂质峰面积不得大于对照溶液主峰面积的0.5倍(0.5％)，各杂质峰面积的和不得大于对照溶液主峰面积的3倍(3.0％)，小于对照溶液主峰面积0.1倍的峰忽略不计。
2.高温稳定性试验
将实施例1-5头孢克肟片、对比实施例1-5头孢克肟片作为供试品，置于60℃下放置20天，分别于第0天、第5天、第10天、第20天取样，检测头孢克肟有关物质总含量的变化。
图1为实施例1-5、对比实施例1-5头孢克肟片光照稳定性试验有关物质总含量变化。图2为实施例1-5、对比实施例1-5头孢克肟片高温稳定性试验有关物质总含量变化。传统的头孢克肟因其对光、高温较为敏感，需要在阴凉通风处避光保存，本发明提供的头孢克肟脂质体片剂克服了包装、贮存条件苛刻的问题，其对于高温、强光这类激烈条件的敏感度降低，显著提升了头孢克肟的稳定性。
Claims (10)
1.一种头孢克肟片，其特征在于，由头孢克肟脂质体、填充剂、崩解剂、润滑剂、矫味剂组成；其中，所述的填充剂为淀粉和糊精，所述的崩解剂为低取代羟丙纤维素；
所述头孢克肟脂质体的制备方法为：
将1-4重量份磷脂酰乙醇胺、0.5-2重量份的岩藻甾醇溶于有机溶剂，冷冻干燥得到冻干粉末，用溶有1重量份头孢克肟、0.1-0.6重量份三乙醇胺的水溶液水化，超声，过滤，浓缩，得到头孢克肟脂质体。
2.根据权利要求1所述的头孢克肟片，其特征在于，所述有机溶剂选自正丁醇、三氯甲烷、异丙醇中的一种。
3.根据权利要求1所述的头孢克肟片，其特征在于，所述有机溶剂选自正丁醇。
4.根据权利要求1所述的头孢克肟片，其特征在于，所述磷脂酰乙醇胺的用量为2重量份。
5.根据权利要求1所述的头孢克肟片，其特征在于，所述岩藻甾醇的用量为1重量份。
6.根据权利要求1所述的头孢克肟片，其特征在于，所述三乙醇胺的用量为0.3重量份。
7.根据权利要求1所述的头孢克肟片，其特征在于，所述润滑剂选自硬脂酸镁、滑石粉、微粉硅胶、聚乙二醇、氢化植物油中的至少一种。
8.根据权利要求1所述的头孢克肟片，其特征在于，所述润滑剂选自微粉硅胶。
9.根据权利要求1所述的头孢克肟片，其特征在于，所述矫味剂选自甘露醇、蔗糖、三氯蔗糖、阿司帕坦、赤藓糖醇、木糖醇中的至少一种。
10.根据权利要求1所述的头孢克肟片，其特征在于，所述矫味剂选自阿司帕坦。
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101966159A (zh) * | 2010-07-05 | 2011-02-09 | 王丽燕 | 包含头孢克肟脂质体的片剂及其制备方法 |
| CN102327235A (zh) * | 2011-07-14 | 2012-01-25 | 海南美大制药有限公司 | 一种头孢克肟脂质纳米粒固体制剂 |
| CN106466299A (zh) * | 2015-08-19 | 2017-03-01 | 上海本素医药科技有限公司 | 以人参皂苷为膜材的空白脂质体、其制备方法及应用 |
| KR20170035782A (ko) * | 2015-09-23 | 2017-03-31 | 세종대학교산학협력단 | 탁산계 약물 전달용 리포좀 및 이의 제조방법 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CA3024951A1 (en) * | 2015-05-26 | 2016-12-01 | Comfort Care For Animals Llc | Liposome loading |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101966159A (zh) * | 2010-07-05 | 2011-02-09 | 王丽燕 | 包含头孢克肟脂质体的片剂及其制备方法 |
| CN102327235A (zh) * | 2011-07-14 | 2012-01-25 | 海南美大制药有限公司 | 一种头孢克肟脂质纳米粒固体制剂 |
| CN106466299A (zh) * | 2015-08-19 | 2017-03-01 | 上海本素医药科技有限公司 | 以人参皂苷为膜材的空白脂质体、其制备方法及应用 |
| KR20170035782A (ko) * | 2015-09-23 | 2017-03-31 | 세종대학교산학협력단 | 탁산계 약물 전달용 리포좀 및 이의 제조방법 |
Non-Patent Citations (1)
| Title |
|---|
| Nanoparticulate Antibiotic Systems as Antibacterial Agents and Antibiotic Delivery Platforms to Fight Infections;Antonio Vassallo等;《Journal of Nanomaterials》;20200912;1-31 * |
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