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A Study of Optimal Lotion Manufacturing Process Containing Angelica gigas Nakai Extracts by Utilizing Experimental Design and Design Space Convergence Analysis

실험 설계와 디자인 스페이스 융합 분석을 통한 Angelica gigas Nakai 추출물을 함유한 로션 제조의 최적 공정 연구

  • Pyo, Jae-Sung (Department of Pharmacy, Kyungsung University) ;
  • Kim, Hyun-Jin (R&D center, Naturetech Co., Ltd) ;
  • Yoon, Seon-hye (R&D center, Naturetech Co., Ltd) ;
  • Park, Jae-Kyu (Advanced Bio Convergence Center, Pohang Technopark Foundation) ;
  • Kim, Kang-Min (Department of Pharmaceutical Science and Technology, Kyungsung University)
  • Received : 2022.01.04
  • Accepted : 2022.03.20
  • Published : 2022.03.28

Abstract

This study was conducted to identify the optimal lotion manufacturing conditions with decursin and decursinol angelate of Angelica gigas Nakai extraction. Lotion was confirmed that it had viscosity (5,208±112 cPs), assay (99.71±1.01%), and pH (5.62) for 3 months. The optimization of manufacturing conditions of mixing 4 for lotion formulation were made by 22+3 full factorial design. Mixing temperature (40-80℃) and mixing time (10-30 min) were used as independent variables with three responses(assay, pH, and weight variation) as critical quality attributes (CQAs). The model for assay and weight variation identified a proper fit having a determination coefficient of the regression equation (about 0.9) and a p-value less than 0.05. Estimated conditions for the optimal manufacturing process of lotion were 61.93℃ in mixing temperature and 15.85 min in mixing time. Predicted values at the mixing temperature (60℃) and mixing time (20 min) were 100.69% of assay, 5.57 of pH, and 98.07% of weight variation. In the verification of the actual measurement the obtained values showed 100.29±0.98% of assay, 5.57±0.02 of pH, and 98.27±0.89% of weight variation, respectively, in good agreement with predicted values.

본 연구에서는 데커신 및 데커시놀 안젤레이트를 이용한 최적의 로션 제조 공정을 확인하기 위하여 연구를 진행하였다. 초기 로션 제형은 3개월 동안 점도(5,208±112 cPs), 함량(99.71±1.01%) 및 pH(5.62)을 유지하는 것을 확인하였다. 제조 공정D 혼합 4의 최적 제조 공정 확인은 22+3 완전 배치 요인법을 이용하였으며, 독립변수로 혼합 온도(40-80℃)와 혼합 시간(10-30 min)으로 종속변수로써 중요품질특성인 함량, pH, 질량편차를 확인하였다. 함량 및 질량편차는 도출된 회귀방적식의 결정계수는 약 0.9였고 p-value값은 0.05보다 작아 모델적합성을 확인하였다. 로션 제조를 위한 최적의 온도조건과 혼합 시간은 61.93℃와 15.85분으로 확인되었다. 혼합4 공정에 있어 혼합 온도(60℃)와 혼합 시간(15 min)에서의 함량은 100.69%, pH는 5.57, 질량편차는 98.07%으로 예측되었고, 실제 검증에서는 각각 100.29±0.98%, 5.57±0.02, 98.27±0.89%으로 예측된 값에 대하여 유사한 결과까지 확인 할 수 있었다.

Keywords

Acknowledgement

This work was supported by the Technology development Program(S2983880) funded by the Ministry of SMEs and Startups (MSS, Korea).

References

  1. N. S. Kim, D. H. Jung, C. R. Jung, H.-J. Kim, K. S. Jeon & H. W. Park. (2019). Comparison of growth and contents of active ingredients of Angelica gigas Nakai under different cultivation areas. Korean Journal of Plant Resources, 32(5), 448-456. DOI : 10.7732/KJPR.2019.32.5.448
  2. S. H. Lee et al. (2021). Whitening and Antioxidant Effects of Extracts from Angelica gigas Nakai Thin Root. Korean Journal of Plant Resources, 34(1), 37-43. DOI : 10.7732/kjpr.2021.34.1.037
  3. J. M. Ahn, M. J. Ahn, Y. W. Chin & J. W. Kim (2019). Pharmaceutical studies on "Dang-Gui" in korean journals. Natural Product Sciences, 25(4), 285-292. DOI : 10.20307/nps.2019.25.4.285
  4. H. Y., Ahn K. R. Park & Y. S. Cho. (2014). Effect of fermented Angelica gigas Nakai on lipid metabolism in orotic acid model rats. Journal of Life Science, 24(7), 743-749. DOI : 10.5352/JLS.2014.24.7.743
  5. S. I. Park, S. H. Heo, J. S. Lee & M. S. Shin (2021). Extraction of active compounds from Angelica gigas using supercritical carbon dioxide and its physiological activity. Journal of Convergence for Information Technology, 11(6), 206-212. DOI : 10.22156/CS4SMB.2021.11.06.206
  6. A. Chaudhury, D. Barrasso, R. Ramachandran, P. Pandey, H. Wu & R. Ramachandran (2014). Population balance model development, validation, and prediction of CQAs of a high-shear wet granulation process: Towards QbD in drug product pharmaceutical manufacturing. Journal of Pharmaceutical Innovation, 9(1), 53-64. DOI : 10.1007/s12247-014-9172-7
  7. European Medicines Agency. (2009). ICH Q8 (R2) Pharmaceutical development. Retrieved March 25, 2021, (Online). https://www.ema.euro pa.eu/en/ich-q8-r2-pharmaceutical-development
  8. European Medicines Agency. (2006). ICH Q9 Quality risk management. Retrieved April 21, 2021, (Online). https://www.ema.europa.eu/en/ich-q9-quality-risk-management
  9. European Medicines Agency. (2008). ICH guideline Q10 on pharmaceutical quality system. Retrieved April 23, 2021, (Online). https://www.ema.europa.eu/en/ich-q10-pharmaceutical-quality-system
  10. S. E. Jin, M. S. Kim, S. M. Shin, S. H. Jeong & S. J. Hwang. (2014). Current status and understanding of QbD implementation in pharmaceutical industry. FDC Regulatory Sciences, 9(2), 141-148.
  11. J. Y. Kim & K. H. Kwon. (2013). A study on the comparison of korea GMP with PIC/S GMP for enhancing international competency of medicinal product quality. Yakhak Hoeji, 57(6), 432-441.
  12. Ministry of food and drug safety. (2016). Regulations on cosmetic good manufacturing and quality control practices. Retrieved May 15, 2021, (Online). https://www.mfds.go.kr/brd/m_641/view.do?seq=22758&srchFr=&srchTo=&srchWord=&srchTp=&itm_seq_1=0&itm_seq_2=0&multi_itm_seq=0&company_cd=&company_nm=&page=7
  13. B. Aksu, A. Paradkar, M. de Matas, O. Ozer, T. Guneri & P. York. (2012). Quality by design approach: application of artificial intelligence techniques of tablets manufactured by direct compression. AAPS PharmSciTech, 13(4), 1138-1146. DOI : 10.1208/s12249-012-9836-x
  14. R. Bhaumik, N. K. Mondal, S. Chattoraj & J. K. Datta. (2013). Application of response surface methodology for optimization of fluoride removal mechanism by newly developed biomaterial. American Journal of Analytical Chemistry, 4(8), 404-419. DOI : 10.4236/ajac.2013.48051
  15. K. M. Kim. (2021). A study of transdermal permeation of lotion formulation containing Angelica gigas Nakai extracts in franz diffusion cell. Journal of Life Science, 31(11), 1004-1009. DOI : 10.5352/JLS.2021.31.11.1004
  16. Ministry of food and drug safety. (2019). General tests: mass variation test. Retrieved May 15, 2021, (Online). https://www.mfds.go.kr/brd/m_207/view.do?seq=14434&srchFr=&srchTo=&srchWord=&srchTp=&itm_seq_1=0&itm_seq_2=0&multi_itm_seq=0&company_cd=&company_nm=&page=2
  17. M. H. Choi, Y. W. Kim, M. S. Kim & H. J. Shin. (2016). Development of cosmetic emulsion using blueberry fruit extract and agarose from Gracilaria verrucosa. The Korean Society for Biotechnology and Bioengineering, 31(4), 256-262. DOI : 10.7841/ksbbj.2016.31.4.256
  18. Ministry of food and drug safety. (2003). Provision for specifications and test procedures of drugs. The korea food and drug administration notification 2002-43. Retrieved April 23, 2021, (Online). https://mfds.go.kr/brd/m_207/view.do?seq=2192&srchFr=&srchTo=&srchWord=&srchTp=&itm_seq_1=0&itm_seq_2=0&multi_itm_seq=0&company_cd=&company_nm=&page=204
  19. Ministry of food and drug safety. (2007). Regulation on review of specifications and test methods of drugs: specification and test method of weight (volume) variation of drugs. The korea food and drug administration notification 2007-61. Retrieved April 25, 2021, (Online). https://www.law.go.kr/LSW/admRulInfoP.do?admRulSeq=4365
  20. J. H. Kim, K. W. Song, J. O. Lee & C. H. Lee (1995). Studies on the flow properties of semi-solid dosage forms (I): Steady shear flow behavior of toothpastes. Journal of Pharmaceutical Investigation, 25(3), 213-221.
  21. H. Y. Kuk & K. W. Son. (2009). Rheological properties of antiphlamine-S® lotion. Journal of Pharmaceutical Investigation, 39(3), 185-199. DOI : 10.4333/KPS.2009.39.3.185