CN112716921A - 氨磺必利透皮贴剂 - Google Patents
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- 238000013271 transdermal drug delivery Methods 0.000 description 2
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- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
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Abstract
氨磺必利透皮贴剂，包含载药层、背衬层和防粘层，所述载药层由氨磺必利、促渗剂和压敏胶基质组成。载药层中氨磺必利的重量百分比含量为3％～5％。载药层中促渗剂的重量百分比含量为4％～6％，所述促渗剂为重量比10:1～3:0.1～0.2的丙二醇、油酸和薄荷醇。所述压敏胶基质为热熔压敏胶基质。
Description
技术领域
本发明涉及一种经皮给药制剂，尤其是涉及一种以氨磺必利为活性成分的透皮贴剂。
背景技术
氨磺必利(4-氨基-N-[(1-乙基-2-吡咯烷)甲基]-5-乙基磺酰-2-甲氧基苯甲酰胺，CAS：71675-85-9)是一种抗精神病药，临床上主要用于治疗精神分裂症。氨磺必利片在用于治疗时须根据病人的反应调整剂量至最小有效剂量。现有的氨磺必利片剂规格为200mg和50mg两种，固定规格的片剂不利于灵活调节剂量。透皮贴剂作为一种经皮吸收制剂，可以通过皮肤贴敷给药，活性成分经皮肤吸收进入全身血液循环，可以延长作用时间，减少用药次数，用药方便，避免首过效应，减少胃肠道刺激,，且在实际给药过程中，可以采用贴敷不同面积的透皮贴的方式，灵活调节剂量。因此提供氨磺必利透皮贴剂，以提高给药灵活性成为现有技术中亟待解决的问题。
发明内容
为解决前述技术问题，本发明采取的技术方案是：
提供了一种氨磺必利透皮贴剂，其特征是所述透皮贴剂包含载药层、背衬层和防粘层，所述载药层由氨磺必利、促渗剂和压敏胶基质组成。
所述的一种氨磺必利透皮贴剂，其特征是所述载药层中氨磺必利的重量百分比含量为3％～5％。
所述的一种氨磺必利透皮贴剂，其特征是所述载药层中促渗剂的重量百分比含量为4％～6％，所述促渗剂为重量比10:1～3:0.1～0.2的丙二醇、油酸和薄荷醇，所述丙二醇、油酸和薄荷醇的重量比优选为10:1.5～2:0.1～0.15。
所述一种氨磺必利透皮贴剂，其特征是所述压敏胶基质为热熔压敏胶基质。
所述一种氨磺必利透皮贴剂的制备方法，包括以下步骤：
1)将丙二醇、油酸和薄荷醇混合，加入处方量氨磺必利，搅拌至溶解。
2)将步骤1)溶液加入热熔压敏胶基质，搅拌均匀，涂布于防粘层上，于65-85℃干燥后与背衬层复合，切割成贴剂，即得。
本发明提供的氨磺必利透皮贴剂，优选了特定比例的丙二醇、油酸和薄荷醇作为促渗剂体系，并选择热熔压敏胶基质，得到了氨磺必利透皮贴剂。本发明提供的透皮贴剂，能够持续稳定释药，具有用药方便，避免首过效应，减少胃肠道刺激的优点，同时可以通过贴敷不同面积的透皮贴，灵活调节用药量，满足精神类药物需要。
具体实施方式
所有实施例中的百分比均为重量百分含量
实施例1
氨磺必利3％
促渗剂总用量4％，丙二醇、油酸和薄荷醇的重量比为10:1:0.1；余量的热熔压敏胶基质，
配制方法如下
1)将丙二醇、油酸和薄荷醇混合，加入处方量氨磺必利，搅拌至溶解。
2)将步骤1)溶液加入热熔压敏胶基质，搅拌均匀，涂布于防粘层上，于65-85℃干燥后与背衬层复合，切割成贴剂，即得。
实施例2
氨磺必利4％
促渗剂总用量5％，丙二醇、油酸和薄荷醇的重量比为10:3:0.2；余量的热熔压敏胶基质，
配制方法如下
1)将丙二醇、油酸和薄荷醇混合，加入处方量氨磺必利，搅拌至溶解。
2)将步骤1)溶液加入热熔压敏胶基质，搅拌均匀，涂布于防粘层上，于65-85℃干燥后与背衬层复合，切割成贴剂，即得。
实施例3
氨磺必利5％
促渗剂总用量6％，丙二醇、油酸和薄荷醇的重量比为10:1.5:0.1；余量的热熔压敏胶基质，
配制方法如下
1)将丙二醇、油酸和薄荷醇混合，加入处方量氨磺必利，搅拌至溶解。
2)将步骤1)溶液加入热熔压敏胶基质，搅拌均匀，涂布于防粘层上，于65-85℃干燥后与背衬层复合，切割成贴剂，即得。
实施例4
氨磺必利3％
促渗剂总用量6％，丙二醇、油酸和薄荷醇的重量比为10:2:0.15；余量的热熔压敏胶基质，
配制方法如下
1)将丙二醇、油酸和薄荷醇混合，加入处方量氨磺必利，搅拌至溶解。
2)将步骤1)溶液加入热熔压敏胶基质，搅拌均匀，涂布于防粘层上，于65-85℃干燥后与背衬层复合，切割成贴剂，即得。
实施例5
氨磺必利5％
促渗剂总用量4％，丙二醇、油酸和薄荷醇的重量比为10:1.5:0.15；余量的热熔压敏胶基质，
配制方法如下
1)将丙二醇、油酸和薄荷醇混合，加入处方量氨磺必利，搅拌至溶解。
2)将步骤1)溶液加入热熔压敏胶基质，搅拌均匀，涂布于防粘层上，于65-85℃干燥后与背衬层复合，切割成贴剂，即得。
通过对实施例1～5的贴剂进行考察，可知其含量均匀度、释放度、初黏力、持黏力、和剥离强度均符合中国药典2015版二部附录IV贴剂中的相关规定。
药理实施例1氨磺必利透皮贴剂的体外经皮渗透实验。
采用立式扩散池，有效扩散面积为2.8cm2，所用皮肤为去毛猪耳朵皮肤，皮肤厚度约为约600μm。将贴剂贴于去毛猪耳朵皮肤的角质层一侧，置于扩散池与接收池之间，角质层朝向扩散池，真皮层朝向接收池。接收池体积为6.5mL，加满pH7.4PBS并排除气泡，置于循环水浴磁力搅拌池中，磁子转速设为300r/min，水浴温度为37℃。透皮开始后第2h、4h、6h、8h、10h、12h、14h、24h取样1mL，取样后立即补充新鲜的接收液，将取样液用0.45μm微孔滤膜滤过后用高效液相色谱法测定氨磺必利的浓度，计算经皮渗透速率和累积渗透量，结果如下表所示(means±SD，n＝3)
| 组别 | 经皮渗透速率(μg·cm<sup>-2</sup>·h<sup>-1</sup>) | 累计渗透量(μg·cm<sup>-2</sup>) |
| 实施例1 | 0.86±0.14 | 10.34±0.53 |
| 实施例2 | 0.92±0.16 | 10.89±0.67 |
| 实施例3 | 1.08±0.21 | 13.76±0.71 |
| 实施例4 | 0.99±0.13 | 11.33±0.68 |
| 实施例5 | 0.97±0.15 | 11.41±0.71 |
实验结果表明，本发明提供的透皮贴剂，在优选了压敏胶基质和促渗剂的情况下，能够实现氨磺必利的体外透皮给药。
Claims (5)
1.氨磺必利透皮贴剂，其特征是所述透皮贴剂包含载药层、背衬层和防粘层，所述载药层由氨磺必利、促渗剂和压敏胶基质组成。
2.如权利要求1所述的氨磺必利透皮贴剂，其特征是所述载药层中氨磺必利的重量百分比含量为3％～5％。
3.如权利要求1或2所述的氨磺必利透皮贴剂，其特征是所述载药层中促渗剂的重量百分比含量为4％～6％，所述促渗剂为重量比10:1～3:0.1～0.2的丙二醇、油酸和薄荷醇。
4.如权利要求3所述的氨磺必利透皮贴剂，其特征是所述丙二醇、油酸和薄荷醇的重量比为10:1.5～2:0.1～0.15。
5.如权利要求1～4任一所述氨磺必利透皮贴剂，其特征是所述压敏胶基质为热熔压敏胶基质。
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