CN112545998A - 一种艾地骨化醇制剂及其制备方法 - Google Patents

一种艾地骨化醇制剂及其制备方法 Download PDF

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CN112545998A
CN112545998A CN202011556498.1A CN202011556498A CN112545998A CN 112545998 A CN112545998 A CN 112545998A CN 202011556498 A CN202011556498 A CN 202011556498A CN 112545998 A CN112545998 A CN 112545998A
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陈阳生
孙桂玉
刘晓霞
沈鑫
臧云龙
王明刚
王清亭
刘薇
孙青华
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Affiliated Hospital of University of Qingdao
CP Pharmaceutical Qingdao Co Ltd
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Abstract

本发明提供了一种艾地骨化醇缓释颗粒，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

一种艾地骨化醇制剂及其制备方法
技术领域
本发明提供了一种艾地骨化醇缓释颗粒，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
艾地骨化醇用于治疗骨质疏松症，由日本中外制药株式会社和日本正大制药株式联合研制，2011年在日本获批上市。艾地骨化醇是继阿法骨化醇和艾地骨化醇后又一新的用于治疗骨质疏松症的活性维生素D3衍生物，能促进小肠对钙的吸收，增加血钙浓度，同时改善骨代谢和促进钙吸收，疗效优于阿法骨化醇和艾地骨化醇，具有较好的应用前景。
现有的艾地骨化醇制剂主要为软胶囊剂，剂型比较单一，患者选择余地较少。而且软胶囊剂用药次数多，患者耐用性低，使用受限制；从质量上来讲，软胶囊剂普遍存在稳定性不好，长期贮存易吸潮影响崩解和含量，进而影响生物利用度及疗效的问题。
发明内容
本发明为了解决现有艾地骨化醇制剂剂型单一、软胶囊剂服用次数多、崩解慢、起效慢、生物利用度低的缺点，发明了艾地骨化醇缓释颗粒，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艾地骨化醇进行包合，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。
本发明所述艾地骨化醇缓释颗粒，其特征在于由艾地骨化醇缓释微丸组成，缓释微丸再用包合材料包合后制成。原辅料主要包括艾地骨化醇、缓释材料、包合材料、增塑剂、致孔剂和抗粘剂。
本发明所述艾地骨化醇缓释颗粒，其特征在于所述缓释材料为一醋酸纤维素和二醋酸纤维素中的任意一种或组合物；包合材料为α-环糊精、β-环糊精、γ-环糊精中的任意一种或几种；增塑剂为甘油和乙酰柠檬酸三丁酯中的一种或组合物；所述致孔剂为羟丙基甲基纤维素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。
进一步的，缓释材料为二醋酸纤维素；包合材料为β-环糊精；增塑剂为甘油；所述抗粘剂为硬脂酸镁；所述致孔剂为羟丙基甲基纤维素和聚维酮的组合物，且二者比例为3:1。
本发明所述的艾地骨化醇缓释颗粒，其特征在于辅料包括淀粉、微粉硅胶、乙醇。
本发明所述的艾地骨化醇缓释颗粒，其特征在于艾地骨化醇缓释颗粒的处方为：艾地骨化醇10份，缓释材料50-60份，包合材料5-10份，增塑剂5-8份，致孔剂10-15份，抗粘剂15-25份，淀粉20-25份，微粉硅胶5-10份，乙醇适量。
本发明所述的艾地骨化醇缓释颗粒，其特征在于艾地骨化醇缓释颗粒的处方为：艾地骨化醇10份，缓释材料55份，包合材料6份，增塑剂6份，致孔剂12份，抗粘剂18份，淀粉25份，微粉硅胶6份，乙醇适量。
本发明所述的艾地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艾地骨化醇表面，反复喷洒3-5次，形成艾地骨化醇缓释微丸；
C、将艾地骨化醇缓释微丸与包合材料以3:1的摩尔比例制备艾地骨化醇包合物；
D、称取处方量的淀粉，加入蒸馏水，制成淀粉浆，与艾地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，加入微粉硅胶混匀后即得艾地骨化醇缓释颗粒。
本发明在试验过程中意外的发现，先用缓释材料将艾地骨化醇包衣，再采用包合材料进行包合，制颗粒后缓释效果较好。本发明艾地骨化醇缓释颗粒采用先包缓释材料再包合的方式，对难溶于水的艾地骨化醇进行预处理，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（处方为按重量份数比计）：
Figure DEST_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所制得的艾地骨化醇缓释颗粒，按照药典规定法测定，测定结果见表1。
表1 实施例1-6艾地骨化醇缓释颗粒释放度考察表
Figure 836708DEST_PATH_IMAGE002
从试验结果可见，当致孔剂比例一定时，缓释材料中二醋酸纤维素的量越高，缓释效果越好。
实施例7-12（处方为按重量份数比计）：
Figure DEST_PATH_IMAGE002
试验例2 实施例7-12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7-12所制得的艾地骨化醇缓释颗粒，按照药典规定法测定，测定结果见表2。
表2 实施例7-12艾地骨化醇缓释颗粒释放度考察表
Figure 11654DEST_PATH_IMAGE004
从试验结果可见，缓释材料为二醋酸纤维素，同时致孔剂为羟丙基甲基纤维素和聚维酮的组合物，且二者比例为3:1时，缓释效果最好。

Claims (8)

1.一种艾地骨化醇缓释颗粒，其特征在于由艾地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所述的艾地骨化醇缓释颗粒，其特征在于由艾地骨化醇、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所述的缓释材料为一醋酸纤维素和二醋酸纤维素中的任意一种或组合物；包合材料为α-环糊精、β-环糊精、γ-环糊精中的任意一种或几种；增塑剂为甘油和乙酰柠檬酸三丁酯中的一种或组合物；所述致孔剂为羟丙基甲基纤维素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所述的缓释材料为二醋酸纤维素；包合材料为β-环糊精；增塑剂为甘油；所述抗粘剂为硬脂酸镁；所述致孔剂为羟丙基甲基纤维素和聚维酮的组合物，且二者比例为3:1。
5.如权利要求1-4所述的艾地骨化醇缓释颗粒，其特征在于辅料包括淀粉、微粉硅胶、乙醇。
6.如权利要求1-5所述的艾地骨化醇缓释颗粒，其特征在于艾地骨化醇缓释颗粒的处方为：艾地骨化醇10份，缓释材料50-60份，包合材料5-10份，增塑剂5-8份，致孔剂10-15份，抗粘剂15-25份，淀粉20-25份，微粉硅胶5-10份，乙醇适量。
7.如权利要求6所述的艾地骨化醇缓释颗粒，其特征在于艾地骨化醇缓释颗粒的处方为：艾地骨化醇10份，缓释材料55份，包合材料6份，增塑剂6份，致孔剂12份，抗粘剂18份，淀粉25份，微粉硅胶6份，乙醇适量。
8.如权利要求1-6所述的艾地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艾地骨化醇表面，反复喷洒3-5次，形成艾地骨化醇缓释微丸；
C、将艾地骨化醇缓释微丸与包合材料以3:1的摩尔比例制备艾地骨化醇包合物；
D、称取处方量的淀粉，加入蒸馏水，制成淀粉浆，与艾地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，加入微粉硅胶混匀后即得艾地骨化醇缓释颗粒。
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