普通口服固体制剂溶出度试验技术指导原则2015-2-5

0.2mol/L磷酸二氢钾溶液：取27.22g磷酸二氢钾，用水溶解并稀释至1000mL。

0.2mol/L氢氧化钠溶液：取8.00g氢氧化钠，用水溶解并稀释至1000mL。

取250mL 0.2mol/L磷酸二氢钾溶液与下表中规定量的0.2mol/L氢氧化钠溶液混合后，再加水稀释至1000mL，摇匀，即得。

表4 磷酸盐缓冲液

pH值

4.5

5.5 9.0 7.0

5.8 18.0 7.2

6.0 28.0 7.4

6.2 40.5 7.6

6.4 58.0 7.8

6.6 82.0 8.0

0.2mol/L氢氧化钠溶液（mL） 0

pH值

6.8

0.2mol/L氢氧化钠溶液（mL） 112.0 145.5 173.5 195.5 212.0 222.5 230.5

以上为推荐采用的溶出介质配制方法，如有特殊情况，研究者也可根据研究结果采用其他的溶出介质以及相应的配制方法。

三、温度、转速及其他

所有普通口服制剂的溶出试验均应在37±0.5℃的条件下进行。

溶出度试验过程中应采用较缓和的转速，使溶出方法具有更 好的区分能力。一般情况下篮法的转速为50～100 转/分钟；桨 法的转速为50～75转/分钟。

对于容易产生漂浮的片剂或胶囊，在建立溶出度测定方法时

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建议采用篮法。当必须采用桨法时，可使用沉降篮或其他适当的沉降装臵。

参考文献

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2.FDA, 1995, Center for Drug Evaluation and Research, Guidance for Industry: ImmediateRelease Solid Oral Dosage Forms. Scale-up and Post-Approval Changes: Chemistry,Manufacturing and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation [SUPAC-IR], November 1995.

3.Meyer, M. C., A. B. Straughn, E. J. Jarvi, G. C. Wood, F. R. Pelsor, and V. P. Shah, 1992,“The Bioequivalence of Carbamazepine Tablets with a History of Clinical Failures,”Pharmaceutical Research, 9:1612-1616.

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5.Shah, V. P., et al., 1989, “In Vitro Dissolution Profile of Water Insoluble Drug Dosage Forms inthe Presence of Surfactants,”Pharmaceutical Research, 6:612-618.

6.Shah, V. P., et al., 1992,“Influence of Higher Rate of Agitation

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on Release Patterns of Immediate Release Drug Products,”Journal of Pharmaceutical Science, 81:500-503.

7.Shah, V. P., J. P. Skelly, W. H. Barr, H. Malinowski, and G. L. Amidon, 1992,“Scale-up of Controlled Release Products – Preliminary Considerations,”Pharmaceutical Technology, 16(5):35-40.

8.Shah, V. P., et al., 1995,“In Vivo Dissolution of Sparingly Water Soluble Drug Dosage Forms,” International Journal of Pharmaceutics, 125:99-106.

9.Siewert, M., 1995,“FIP Guidelines for Dissolution Testing of Solid Oral Products,”Pharm.Ind. 57:362-369.

10. Skelly, J. P., G. L. Amidon, W. H. Barr, L. Z. Benet, J. E. Carter, J. R. Robinson, V. P. Shah, and A. Yacobi, 1990,“In Vitro and In Vivo Testing and Correlation for Oral Controlled/Modified-Release Dosage Forms,”Pharmaceutical Research, 7:975-982.

11. 国家食品药品监督管理局，已上市化学药品变更研究的技术指导原则（一），2008.

12.中国药典2010版二部附录，溶出度测定法。

13. British Pharmacopeia 2012，Dissolution test for tablets and capsules.

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