CN114209666A - 一种醋酸泼尼松片及其制备方法 - Google Patents
一种醋酸泼尼松片及其制备方法 Download PDFInfo
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- CN114209666A CN114209666A CN202111487223.1A CN202111487223A CN114209666A CN 114209666 A CN114209666 A CN 114209666A CN 202111487223 A CN202111487223 A CN 202111487223A CN 114209666 A CN114209666 A CN 114209666A
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- prednisone acetate
- magnesium stearate
- tablet
- silicon dioxide
- prednisone
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- MOVRKLZUVNCBIP-RFZYENFJSA-N cortancyl Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)CC2=O MOVRKLZUVNCBIP-RFZYENFJSA-N 0.000 title claims abstract description 45
- 238000002360 preparation method Methods 0.000 title abstract description 18
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 50
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 26
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 25
- 235000012239 silicon dioxide Nutrition 0.000 claims abstract description 13
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- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims abstract description 10
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- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 2
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- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
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- LRJOMUJRLNCICJ-JZYPGELDSA-N Prednisolone acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O LRJOMUJRLNCICJ-JZYPGELDSA-N 0.000 description 1
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- RKHQGWMMUURILY-UHRZLXHJSA-N cortivazol Chemical compound C([C@H]1[C@@H]2C[C@H]([C@]([C@@]2(C)C[C@H](O)[C@@H]1[C@@]1(C)C2)(O)C(=O)COC(C)=O)C)=C(C)C1=CC1=C2C=NN1C1=CC=CC=C1 RKHQGWMMUURILY-UHRZLXHJSA-N 0.000 description 1
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Abstract
本发明属于药物制备技术领域，公开了一种醋酸泼尼松片，其包括以下重量百分比组分：醋酸泼尼松5.39%、乳糖63.91%、玉米淀粉20%、麦芽糖糊精10%、硬脂酸镁0.5%和二氧化硅0.2%。本发明醋酸泼尼松片中乳糖作为稀释剂可提供良好的可压性和流动性；玉米淀粉作为崩解剂促进片剂崩解；麦芽糊精作为粘合剂可提供良好的粘合作用，二氧化硅作为助流剂可提高颗粒流动性和松密度；硬脂酸镁有利于压片时出片，减少颗粒间摩擦力，防止出现涩冲现象，起到润滑的作用，从而保证压片顺利进行。
Description
技术领域
本发明属于药物制备技术领域，涉及一种醋酸泼尼松片及其制备方法。
背景技术
泼尼松是肾上腺皮质激素类药，主要用于过敏性与炎症性疾病。是临床上常用的口服皮质激素，在治疗系统性红斑狼疮、风湿病、肾病综合征等自身免疫性疾病中是最重要的药物；也是某些肿瘤、白血病等恶性肿瘤化疗方案中的药物，具有良好的治疗效果。
泼尼松常用其醋酸酯，为白色或几乎白色结晶性粉末；无臭、味苦。在氯仿中易溶，在丙酮中略溶，在乙醇或乙酸乙酯中微溶，在水中几乎不溶。
醋酸泼尼松具有抗炎及抗过敏作用，能抑制结缔组织的增生，降低毛细血管壁和细胞膜的通透性，减少炎性渗出，并能抑制组胺及其它毒性物质的形成与释放。当严重中毒感染时，与大量抗菌药物配合使用，可有良好的降温、抗毒、抗炎、抗休克及促进症状缓解作用。其水钠潴留及排钾作用比可的松小，抗炎及抗过敏作用较强，副作用较少，故比较常用。临床上可用于各种急性严重细菌感染、严重的过敏性疾病、胶原性疾病(红斑狼疮、结节性动脉周围炎等)、风湿病、肾病综合征、严重的支气管哮喘、血小板减少性紫癜、粒细胞减少症、急性淋巴性白血病、各种肾上腺皮质功能不足症、剥脱性皮炎、天疱疮、神经性皮炎、湿疹等。
醋酸泼尼松作为药物的活性成分，当其制备成口服制剂时，只有醋酸泼尼松能快速而高效地溶于水中才能在胃肠中得到良好的吸收，否则它的吸收和生物利用会有很大的障碍。因此，通过对处方和工艺进行优化，得到溶出较快的醋酸泼尼松口服固体制剂显的非常重要。
通常情况下，醋酸泼尼松采用湿法制粒工艺，压片成型后被服用，这种虽然能够实现醋酸泼尼松的制作成型，但药物的有效性大大折扣，压片成型的水分含量过高就会导致醋酸泼尼松直接溶解，不被人体吸收，同时这种压片若脆性较大，不易被人体吸收消化，若脆弱性较小，就会导致制作成型度困难，不易工业化制片成型。
申请公开号为CN104721160A的发明专利公开了一种醋酸泼尼松龙片剂及其制备方法，该发明首先利用固体分散技术制备醋酸泼尼松分散体，就是将醋酸泼尼松、聚维酮K30溶于乙醇溶液中，再加入甘露醇，减压干燥制备醋酸分散体，然后与其他辅料混匀后直接压片制得。该方法制备工艺复杂，且过程需要用到乙醇溶液、减压干燥等工序，势必会影响制剂稳定性，不利于工业化生产。
申请公开号为CN110840854A的发明专利公开了一种醋酸泼尼松片及其制备方法，该发明首先将醋酸泼尼松微粉化处理，然后通过湿法制粒、干法制粒、压片制得，但制备工艺复杂，且湿法制粒不利于醋酸泼尼松的稳定，不适合工业化生产。
发明内容
本发明的目的在于提供一种醋酸泼尼松片及其制备方法，通过改进处方和工艺，所得醋酸泼尼松片能满足药物快速溶出要求、质量稳定，适用于工业化生产。
为实现上述目的，本发明采用以下技术方案：
本发明提供一种醋酸泼尼松片，包括以下重量百分比组分：醋酸泼尼松5.39％、乳糖63.91％、玉米淀粉20％、麦芽糖糊精10％、硬脂酸镁0.5％和二氧化硅0.2％。
本发明还提供上述醋酸泼尼松片的制备方法，包括以下步骤：
1)将处方量的醋酸泼尼松、二氧化硅、硬脂酸镁分别过40目筛网；
2)称取处方量的醋酸泼尼松、乳糖、玉米淀粉、麦芽糖糊精置混合机中混合10min；
3)称取一半处方量的硬脂酸镁加入混合机中与步骤2)中物料一起混合5min；
4)将步骤3)中所得物料在干压机上干压1次，过20目筛，得干颗粒；干压机的轧辊间隙1.5～3.0mm、油泵压力23～37bar、送料转速25～35rpm、轧辊转速10rpm、整粒转速100rpm、整粒筛网1.0～1.5mm；
5)将处方量的二氧化硅和另一半处方量的硬脂酸镁用量与干颗粒一起在多向运动混合机中混合5min；
6)压片；
7)包衣。
优选地，步骤7)中控制包衣增重2％～5％。
相比现有技术，本发明的有益效果在于：
本发明醋酸泼尼松片中乳糖作为稀释剂可提供良好的可压性和流动性；玉米淀粉作为崩解剂促进片剂崩解；麦芽糊精作为粘合剂可提供良好的粘合作用，二氧化硅作为助流剂可提高颗粒流动性和松密度；硬脂酸镁有利于压片时出片，减少颗粒间摩擦力，防止出现涩冲现象，起到润滑的作用，从而保证压片顺利进行。本发明中醋酸泼尼松片制备工艺过程为：原料与乳糖、玉米淀粉、麦芽糖糊精先混合、加入内加部分硬脂酸镁混合后，进行干法制粒，再加入外加部分二氧化硅和硬脂酸镁总混、压片，包衣。本发明通过改进处方和工艺，所得醋酸泼尼松片能满足药物快速溶出要求、质量稳定，适用于工业化生产。
具体实施方式
以下实施例用于说明本发明，但不用来限定本发明的保护范围。若未特别指明，实施例中所用技术手段为本领域技术人员所熟知的常规手段。下述实施例中的试验方法，如无特别说明，均为常规方法。
实施例1
醋酸泼尼松片处方量：醋酸泼尼松5.39mg、乳糖63.91mg、玉米淀粉20mg、麦芽糖糊精10mg、硬脂酸镁0.5mg和二氧化硅0.2mg。
上述醋酸泼尼松片的制备方法，包括以下步骤：
1)将处方量的醋酸泼尼松、二氧化硅、硬脂酸镁分别过40目筛网；
2)称取处方量的醋酸泼尼松、乳糖、玉米淀粉、麦芽糖糊精置混合机中混合10min；
3)称取一半处方量的硬脂酸镁加入混合机中与步骤2)中物料一起混合5min；
4)将步骤3)中所得物料在干压机上干压1次，过20目筛，得干颗粒；干压机的轧辊间隙1.5～3.0mm、油泵压力28～32bar、送料转速30rpm、轧辊转速10rpm、整粒转速100rpm、整粒筛网1.0mm；
5)将处方量的二氧化硅和另一半处方量的硬脂酸镁用量与干颗粒一起在多向运动混合机中混合5min；
6)压片：冲模规格8.5*4.5mm，骨头形，控制片硬度3-5kg；
7)包衣：用高效薄膜衣包衣机进行包衣，包衣粉型号：295F680018，控制包衣增重2％-5％。
实施例2～3
表1实施例2～3的处方量及干压参数
实施例1～3检测结果
1.溶出方法
表2实施例1～3的溶出方法
| 装置 | 转速 | 介质 | 体积 | 取样点 |
| 桨法 | 50rpm | 0.1mol/L盐酸溶液 | 500mL | 5、10、15、30、45min |
| 桨法 | 50rpm | pH4.5醋酸盐缓冲液 | 500mL | 5、10、15、30、45min |
| 桨法 | 50rpm | pH6.8磷酸盐缓冲液 | 500mL | 5、10、15、30、45min |
2.溶出结果
表3实施例1～3的溶出结果(n＝12)
实施例1的加速试验稳定性考察结果如表4所示。
表4实施例1的加速试验稳定性考察结果
为与本发明干法制粒进行对比，采用以下处方量作为对比例：醋酸泼尼松0.05kg、玉米淀粉0.3kg、羧甲淀粉钠0.22kg、糖粉0.25kg、淀粉浆(8％)约0.1kg和硬脂酸镁0.008kg，采用湿法工艺制成10000片，具体步骤如下：
1)称取处方量的原辅料，备用。
2)先将玉米淀粉与醋酸泼尼松依次放入槽型混合机中等量递加稀释2次，作为预混合粉备用。根据槽型混合机的容量将预混合粉平均分配，将分配好的预混合粉及处方量剩余的淀粉、糖粉、内加羧甲淀粉钠放入槽型混合机料缸中，启动搅拌桨进行干粉混合，混合25min，作为混合粉，然后加适量淀粉浆(8％)制成软材。用18目筛制粒，干燥温度60～70℃。颗粒水份4.0～7.0％。
3)干颗粒加处方量的羧甲淀粉钠、硬脂酸镁，用Ф0.8～1.0mm筛网整粒。将整好的颗粒放入二维混合机中混合25分钟。
4)压片：冲模规格8.5*4.5mm，骨头形，控制片硬度3-5kg；
5)包衣：用高效薄膜衣包衣机进行包衣，包衣粉型号：295F680018或295N630001，控制包衣增重2％-5％。
对比例的稳定性考察结果如表5所示。
表5对比例的加速试验稳定性考察结果
通过表4和表5可知，原湿法工艺醋酸泼尼松片的醋酸泼尼松含量较本发明低，且稳定性较本发明差。
以上所述之实施例，只是本发明的较佳实施例而已，仅仅用以解释本发明，并非限制本发明实施范围，对于本技术领域的技术人员来说，当然可根据本说明书中所公开的技术内容，通过置换或改变的方式轻易做出其它的实施方式，故凡在本发明的原理上所作的变化和改进等，均应包括于本发明申请专利范围内。
Claims (3)
1.一种醋酸泼尼松片，其特征在于，包括以下重量百分比组分：醋酸泼尼松5.39%、乳糖63.91%、玉米淀粉20%、麦芽糖糊精10%、硬脂酸镁0.5%和二氧化硅0.2%。
2.权利要求1所述的一种醋酸泼尼松片的制备方法，其特征在于，包括以下步骤：
1）将处方量的醋酸泼尼松、二氧化硅、硬脂酸镁分别过40目筛网；
2）称取处方量的醋酸泼尼松、乳糖、玉米淀粉、麦芽糖糊精置混合机中混合10min；
3）称取一半处方量的硬脂酸镁加入混合机中与步骤2）中物料一起混合5min；
4）将步骤3）中所得物料在干压机上干压1次，过20目筛，得干颗粒；干压机的轧辊间隙1.5~3.0mm、油泵压力23~37bar、送料转速25~35rpm、轧辊转速10rpm、整粒转速100rpm、整粒筛网1.0~1.5mm；
5）将处方量的二氧化硅和另一半处方量的硬脂酸镁用量与干颗粒一起在多向运动混合机中混合5min；
6）压片；
7）包衣。
3.根据权利要求2所述的一种醋酸泼尼松片的制备方法，其特征在于，步骤7）中控制包衣增重2%~5%。
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