Journal of the Korea Academia-Industrial cooperation Society (한국산학기술학회논문지)

The Korea Academia-Industrial cooperation Society (한국산학기술학회)
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The in-use stability study of multi-use ophthalmic solutions -Focused on Olopatadine, Fluorometholone, Dorzolamide, Timolol-

다회용 점안제의 개봉 후 안정성 평가 -올로파타딘, 플루오로메톨론, 도르졸라미드, 티몰롤 약물 중심-

  • Shin, Seo-young (School of Pharmacy, Sungkyunkwan University) ;
  • Jang, Kyoung won (Department of Pharmaceutical Quality, Daewon University College) ;
  • Sun, Sangouk (Department of Pharmaceutical Engineering, Dongshin University) ;
  • Ha, Dongmun (School of Pharmacy, Sungkyunkwan University)
  • 신서영 (성균관대학교 약학대학) ;
  • 장경원 (대원대학교 제약품질관리과) ;
  • 선상욱 (동신대학교 제약공학과) ;
  • 하동문 (성균관대학교 약학대학)
  • Received : 2018.10.15
  • Accepted : 2019.02.01
  • Published : 2019.02.28
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Abstract

Multi-use ophthalmic solutions are used many times after opening; therefore, there is a high possibility of decreased quality during use. This study was conducted to determine the recommended use period of multi-use ophthalmic solutions based on evaluation of the stability by comparing stability evaluation regulations of the USA, EU and Korea We selected four types of multi-use ophthalmic solutions (Olopatadine (Olo), Fluorometholone (Flu), Dorzolamide (Dor), Timolol (Timol)) that are frequently marketed in Korea and evaluated their stability during storage according to the actual usage method after opening. The Olo had a decrease in assay and preservative content at 2 months after opening, while Flu showed a significant difference from day 28 after opening. For Dor, significant differences were observed from day 14 after opening in the assay and impurity test item and Timol showed a significant difference from day 28 after opening. Based on the results of the stability test Olo and Flu should only be used within 28 days of opening, while Dor and Timol should be used within 14 days of opening. Therefore, we suggest that regulations system related use periods of multi-use ophthalmic solutions designed as aseptic preparations should be improved based on the results of stability tests after opening.

다회용 점안제는 개봉 후 여러 번 사용되기 때문에 사용 중 품질저하 가능성이 높다. 다회용 점안제의 개봉 후 안정성 평가 관련 국내외 규정의 비교분석을 통해 제제별 안정성을 평가하여 개봉 후 안전한 사용기간을 제안하고자 한다. 국내에서 다빈도로 사용중인 다회용 점안제 4종(올로파타딘염산염(Olo), 플루오로메톨론(Flu), 도르졸라미드염산염(Dor), 티몰롤말레산염(Timol))을 대상으로 개봉 후 실제 사용방법에 따른 보관조건을 통해 안정성을 평가하였다. 연구결과 Olo는 개봉 2개월 이후 주성분 및 보존제 함량이 감소하였고, Flu는 개봉 후 28일 차부터 함량이 감소되었다. Dor와 Timol 복합점안제의 경우 Dor은 함량 및 유연물질이 개봉 후 14일부터, Timol의 함량은 개봉 후 28일부터 안정성 저하를 보였다. Olo, Flu은 개봉 후 28일 이내로, Dor, Timol은 개봉 후 14일 이내에만 사용되어야 한다. 무균제제인 다회용 점안제는 개봉 후 안정성 평가를 통해 사용기간 설정에 대한 규제제도 개선이 필요함을 제언하고자 한다.

Keywords

Table 1. 2016, 3Q, IMS health data, Market share of ophthalmic solutions.

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Table 2. Characteristic of ophthalmic solutions for in-use stability study after opening.

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Table 3. In-use stability test design for determining beyond-use date of study ophthalmic solutions.

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Table 4. HPLC conditions for in-use stability test of study products.

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Table 5. In-use stability result of ophthalmic solutions at storage temperature 2~8℃.

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Table 6. In-use stability result of ophthalmic solutions at storage temperature RT(room temperature).

SHGSCZ_2019_v20n2_681_t0006.png 이미지

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