시뮬레이션 디자인을 적용한 플로로글루시놀 설하정과 니트로글리세린 설하정의 개봉 후 안정성 평가 = In-use Stability Study of Phloroglucinol and Nitroglycerin Sublingual Tablets Using Simulation Design after Opening of their Containers

다국어 초록 (Multilingual Abstract)

Expiration date of pharmaceuticals is established based on stability studies on the products. However it does notguarantee stability of pharmaceuticals once their containers are open. In particular pharmaceuticals stored in multi-dose containeror the ones which require protection from moisture (e.g. sublingual tablets, effervescent tablets and dispersible tablets)need information on in-use stability after opening of their containers to maintain their safety, efficacy, and quality. It helps consumersto take pharmaceuticals safely. In order to study in-use stability of pharmaceuticals after opening of their containers,Phloroglucinol sublingual tablets and Nitroglycerin sublingual tablets which are sensitive to moisture or humidity wereselected. Test methods were developed referring to the applicable EMA guideline, including withdrawal method to consideractual use of pharmaceuticals. The appearance, disintegration and potency of the Phloroglucinol sublingual tablets were evaluatedat 1, 3 and 6 month after opening of containers. During 6 months, no difference in appearance and disintegration wasfound in different 3 lots. However, the potency of active ingredient was decreased gradually during 6 months and the resultsof 3 lots were 93.4%, 94.1% and 94.2%, respectively, which were out of in-house specification range (95.0~105.0%) of testproduct. In-use stability of Nitroglycerin sublingual tablets was also evaluated on appearance, disintegration, impurity andpotency at 0.5, 1, 2, 3 and 6 month after opening of containers. During 6 months, no significant difference in appearance, disintegrationand impurity were found in different 3 lots. However, the potency of active ingredient was decreased graduallyduring 6 months and the results of 3 lots was 82.1%, 83.2% and 84.1%, respectively, even though they were remained withinthe KP specification range (80.0~120.0%) of test product. Study results suggest product quality of sublingual tablets can beaffected by opening of their containers. For safe and effective use of pharmaceuticals, we recommend the Phloroglucinol sublingualtablets and Nitroglycerin sublingual tablets be stored under the minimized moisture effect and used within 6 monthsafter opening of their containers

참고문헌 (Reference)

1 U.S. Pharmacopoeia National Formulary, "USP Monographs: Nitroglycerin Subligual Tablets" U.S. Pharmacopoeial Convention 2017

2 U.S. Pharmacopoeia National Formulary, "USP General Chapters: <795> Pharmaceutical Compounding-Nonsterile Preparations" U.S. Pharmacopoeial Convention 2017

3 "The Korean Pharmacopoeia eleven edition (2017-63)"

4 EMA, "Note for guidance on in-use stability testing of human medicinal products" 2001

5 National Institute of Food and Drug Safety Evaluation, "Guidance for in-use stability testing of pharmaceuticals after opening of their conatiners" 2016

6 Yongsheng Y, "Comparative stability of repackaged metoprolol tartrate tablets" 385 : 92-, 2010