CN112545997A - 一种氟骨化醇制剂及其制备方法 - Google Patents

一种氟骨化醇制剂及其制备方法 Download PDF

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CN112545997A
CN112545997A CN202011556315.6A CN202011556315A CN112545997A CN 112545997 A CN112545997 A CN 112545997A CN 202011556315 A CN202011556315 A CN 202011556315A CN 112545997 A CN112545997 A CN 112545997A
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陈阳生
孙桂玉
臧云龙
刘晓霞
王明刚
杜昌余
刘薇
朱锐
刘鹏新
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CP Pharmaceutical Qingdao Co Ltd
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Abstract

本发明提供了一种氟骨化醇缓释颗粒，属医药技术领域。本发明先将药物用缓释材料制成微粒，再利用包合技术将难溶微粒包合，加入适量的辅料制备颗粒，工艺简单，药物稳定，给药频率少，患者顺应性增强，可缓慢释放药物的缓释制剂。

Description

一种氟骨化醇制剂及其制备方法
技术领域
本发明提供了一种氟骨化醇缓释颗粒，属医药技术领域。本发明先将药物用缓释材料制成微粒，再利用包合技术将难溶微粒包合，加入适量的辅料压颗粒，工艺简单，药物稳定，给药频率少，患者顺应性增强，可缓慢释放药物的缓释制剂。
背景技术
氟骨三醇，是维生素D3类似物，是小肠活性形式的衍生物，通过结合到分布在靶组织中的受体发挥作用，本品可调节钙代谢、抗佝偻病，用于治疗甲状旁腺功能减退症。现有的氟骨三醇制剂主要为片剂，氟骨化三醇片最早2001年4月由日本住友与日本大正制药共同研发上市；在其他国家均未上市。
甲状旁腺是多位于人体颈前部甲状腺侧叶后方的内分泌腺体，约80%的人有4个甲状旁腺，甲状旁腺分泌的激素主要为甲状旁腺素，它主要调节人体内钙磷代谢和骨骼代谢。甲状旁腺功能减退症简称甲旁减，因多种原因导致甲状旁腺素产生减少或作用缺陷而造成以低钙血症、高磷血症为主要化验异常，患者表现为反复手足搐搦和癫痫发作，长期口服钙剂和维生素D制剂以使病情得到控制。
现有的氟骨化醇制剂主要为片剂，剂型比较单一，患者选择余地较少。而且不便于老年患者或不方便吞咽的患者使用；现有的氟骨化醇片用药次数多，患者耐用性低，使用受限制；且片剂崩解时间较长，生物利用度低。
发明内容
本发明为了解决现有氟骨化醇制剂剂型单一、服用次数多、崩解慢、起效慢、生物利用度低的缺点，发明了氟骨化醇缓释颗粒，先将药物用缓释材料制成微粒，再采用特定的包合材料将难溶于水的氟骨化醇进行包合，包合后后可溶于水，易于制备颗粒，并在体内缓慢释放，血药浓度稳定。
本发明所述一种氟骨化醇缓释颗粒，其特征在于由氟骨化醇缓释微丸组成，缓释微丸再用包合材料包合后制成。原辅材料包括氟骨化醇、缓释材料、包合材料、增塑剂、致孔剂和抗粘剂、辅料组成。
本发明所述的缓释材料为羧甲基纤维素钠和氧化淀粉的组合物；包合材料为α-环糊精、β-环糊精、γ-环糊精、羧甲基-β-环糊精中的任意一种或几种；增塑剂为邻苯二甲酸二乙酯；所述致孔剂为聚乙二醇400和聚维酮中的一种或组合物；所述抗粘剂为硬脂酸镁和二氧化硅中的一种或组合物。
本发明所述的羧甲基纤维素钠和氧化淀粉比例为7:1；包合材料为羧甲基-β-环糊精；所述抗粘剂为二氧化硅；所述致孔剂为聚乙二醇400。
本发明所述的氟骨化醇缓释颗粒，其特征在于辅料包括乳糖、滑石粉、乙醇。
本发明所述的氟骨化醇缓释颗粒，其特征在于氟骨化醇缓释颗粒的处方按重量百分比为：氟骨化醇0.2%，缓释材料25-50%，包合材料1-2%，增塑剂10-15%，致孔剂15-18%，抗粘剂20-30%，乳糖20-30%，滑石粉5-10%，乙醇适量。
更进一步的，其特征在于氟骨化醇缓释颗粒的处方按重量百分比为：氟骨化醇0.2%，缓释材料40%，包合材料1%，增塑剂12%，致孔剂16%，抗粘剂24%，乳糖25%，滑石粉胶6%，乙醇适量。
本发明所述的氟骨化醇缓释颗粒的制备方法，其特征在于，该方法包括如下步骤：
A、用50-75%的乙醇溶液溶解缓释材料、增塑剂、致孔剂、抗粘剂，制成缓释包衣液；
B、将配好的缓释包衣液均匀喷洒在氟骨化醇表面，反复喷洒3-5次，形成氟骨化醇缓释微丸；
C、将氟骨化醇缓释微丸与包合材料以2:1的摩尔比例制备氟骨化醇包合物；
D、称取处方量的乳糖，加入蒸馏水，混合后加入氟骨化醇包合物，混合均匀制成软材，20目筛制粒，干燥后过筛整粒，加入滑石粉混匀后即得氟骨化醇缓释颗粒。
本发明在试验过程中意外的发现，先用缓释材料将氟骨化醇包衣，再采用包合材料进行包合，制颗粒后缓释效果较好。本发明氟骨化醇缓释颗粒采用先包缓释材料再包合的方式，对难溶于水的氟骨化醇进行预处理，再加入辅料制备颗粒剂，包合后后可溶于水，易于制备颗粒，并在体内缓慢释放，血药浓度稳定。
具体实施方式
实施例1-6（处方为按重量比计）：
Figure 489742DEST_PATH_IMAGE001
试验例1 实施例1-6释放度测定
根据《中华人民共和国药典》2015年版中“缓、控释制剂指导原则”，以0.25%十二烷基硫酸钠为释放介质，分别精密称取实施例1-6所制得的氟骨化醇缓释颗粒，按照药典规定法测定，测定结果见表1。
表1 实施例1-6氟骨化醇缓释颗粒释放度考察表
Figure 938041DEST_PATH_IMAGE002
从试验结果可见，缓释材料为羧甲基纤维素钠和氧化淀粉，且二者比例为7:1时，缓释效果最好。

Claims (8)

1.一种氟骨化醇缓释颗粒，其特征在于由氟骨化醇缓释微丸组成，缓释微丸再用包合材料包合后制成。
2.如权利要求1所述的氟骨化醇缓释颗粒，其特征在于由氟骨化醇、缓释材料、包合材料、增塑剂、致孔剂和抗粘剂、辅料组成。
3.如权利要求1-2所述的缓释材料为羧甲基纤维素钠和氧化淀粉的组合物；包合材料为α-环糊精、β-环糊精、γ-环糊精、羧甲基-β-环糊精中的任意一种或几种；增塑剂为邻苯二甲酸二乙酯；所述致孔剂为聚乙二醇400和聚维酮中的一种或组合物；所述抗粘剂为硬脂酸镁和二氧化硅中的一种或组合物。
4.如权利要求1-3所述的羧甲基纤维素钠和氧化淀粉比例为7:1；包合材料为羧甲基-β-环糊精；所述抗粘剂为二氧化硅；所述致孔剂为聚乙二醇400。
5.如权利要求1-4所述的氟骨化醇缓释颗粒，其特征在于辅料包括乳糖、滑石粉、乙醇。
6.如权利要求1-5所述的氟骨化醇缓释颗粒，其特征在于氟骨化醇缓释颗粒的处方按重量百分比为：氟骨化醇0.2%，缓释材料25-50%，包合材料1-2%，增塑剂10-15%，致孔剂15-18%，抗粘剂20-30%，乳糖20-30%，滑石粉5-10%，乙醇适量。
7.如权利要求6所述的氟骨化醇缓释颗粒，其特征在于氟骨化醇缓释颗粒的处方按重量百分比为：氟骨化醇0.2%，缓释材料40%，包合材料1%，增塑剂12%，致孔剂16%，抗粘剂24%，乳糖25%，滑石粉6%，乙醇适量。
8.如权利要求1-6所述的氟骨化醇缓释颗粒的制备方法，其特征在于，该方法包括如下步骤：
A、用50-75%的乙醇溶液溶解缓释材料、增塑剂、致孔剂、抗粘剂，制成缓释包衣液；
B、将配好的缓释包衣液均匀喷洒在氟骨化醇表面，反复喷洒3-5次，形成氟骨化醇缓释微丸；
C、将氟骨化醇缓释微丸与包合材料以2:1的摩尔比例制备氟骨化醇包合物；
D、称取处方量的乳糖，加入蒸馏水，混合后加入氟骨化醇包合物，混合均匀制成软材，20目筛制粒，干燥后过筛整粒，加入滑石粉混匀后即得氟骨化醇缓释颗粒。
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