히드록시프로필 메틸셀룰로오스와 에틸셀룰로오스를 이용한 고분자 기반 서방형 비타민 C 정제 설계 및 용출 규격 설정

김현균; 신기형; 구윤태; 김창현; 권석형; 정재철; 최영욱; Hyeon Kyun Kim; Gi Hyeong Sin; Yoon Tae Goo; Chang Hyun Kim; Suk Hyung Kwon; Jae Chul Jung; Young Wook Choi

Polymer(Korea), Vol.46, No.2, 229-237, March, 2022

DOI10.7317/pk.2022.46.2.229 Export Citation

히드록시프로필 메틸셀룰로오스와 에틸셀룰로오스를 이용한 고분자 기반 서방형 비타민 C 정제 설계 및 용출 규격 설정

Polymer-based Sustained Release Tablets of Vitamin C Using Hydroxypropyl Methylcellulose and Ethylcellulose and Their Dissolution Tolerances

김현균, 신기형, 구윤태, 김창현, 권석형¹, 정재철¹, 최영욱^†

중앙대학교 약학대학
¹주식회사 노바렉스

Hyeon Kyun Kim, Gi Hyeong Sin, Yoon Tae Goo, Chang Hyun Kim, Suk Hyung Kwon¹, Jae Chul Jung¹, and Young Wook Choi^†

College of Pharmacy, Chung-Ang University, 84 Heuksuk-ro, Dongjak-gu, Seoul 06974, Korea
¹Novarex Co., Ltd., Osong-eup, Heungdeok-gu, Cheongju-si, Chungbuk-do, Korea

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초록

본 연구에서는 서방형 비타민 C의 용출 규격 설정과 적절한 제형을 추천하기 위하여 서방형 비타민 C 정제 를 개발하였다. 직타법을 이용한 히드록시프로필 메틸셀룰로오스 정제(HTs)와 에틸셀룰로오스로 유동층 코팅된 과 립을 타정한 정제(ETs)가 제조되었다. 시판 제품 3종을 대상으로 비타민 C의 분해를 방지하기 위해 5% 메타인산 수용액 조건하에 수행된 비타민 C 용출 양상을 확보하였다. 해당 용출 양상을 기준선으로 하여, 유사성 인자(f2)를 통해 여러 제형의 비타민 C 용출 양상을 비교하였다. 최종 선택된 제형(HT7과 ET1)은 Korsmeyer-Peppas 모델에 근거한 약물 방출 메커니즘을 따르며, 이들의 용출 양상은 기준선 대비 ±15% 이내의 범위에 분포함을 확인하였다. 결과적으로 서방형 비타민 C에 대한 용출 규격은 15-40%(1시간), 25-70%(3시간), 50-90%(5시간), 그리고 80% 이 상(8시간)의 용출범위 내에서 설정되었다.

In this study, we developed sustained release tablets of vitamin C (ascorbic acid, AA) to establish dissolution tolerances and recommend appropriate formulations. We fabricated hydroxypropyl methylcellulose (HPMC) matrix tablets (HTs) and ethylcellulose (EC)-pelletized tablets (ETs) using direct compression and/or fluidized coating. Along with three commercially available products for reference, we acquired the AA dissolution profiles of the prepared samples in 5% metaphosphoric acid aqueous solution to prevent the degradation of AA. We then compared the release patterns using the similarity factor (f2). The selected two formulations (HT7 and ET1) showed drug release within the limit of ±15% of the reference curve, followed by the Korsmeyer-Peppas model. We found that the range of dissolution tolerance for the sustained release formulation was 15-40% (1 h), 25-70% (3 h), 50-90% (5 h), and ≥80% (8 h).

Keywords:vitamine C;hydroxypropyl methylcellulose;ethylcellulose;matrix tablet;dissolution tolerance

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[2] Olmedo JM, Yiannias JA, Windgassen EB, Gornet MK, Int. J. Dermatol., 45, 909 (2006)

[3] Gordon BL, Galati J, Yang S, Katz PO, Scherl EJ, ACG Case Rep. J., 7, e00424 (2020)

[4] McGregor GP, Biesalski HK, Curr. Opin. Clin. Nutr. Metab. Care, 9, 697 (2006)

[5] Choi KM, Hoon KM, Won HT, Kim JD, Kim MY, Jung YR, Shin HS, Anal. Sci. Technol., 29, 162 (2016)

[6] Hill A, Wendt S, Benstoem C, Neubauer C, Meybohm P, Langlois P, Adhikari NKJ, Heyland DK, Stoppe C, Nutrients, 10, 974 (2018)

[7] Cha JH, Hong JK, Lee SW, Cha JU, Ko WH, Baek HH, Park HJ, Korean J. Food Sci. Technol., 44, 274 (2012)

[8] Perrie Y, Rades T, Controlled-Release Dosage Forms. FASTtrack Pharmaceutics: Drug Delivery and Targeting; Pharmaceutical Press: London, pp 119-139, 2012.

[9] Ray B, Gupta MM, J. Drug Delivery Ther., 3, 55 (2013)

[10] Jaimini M, Kothari A, J. Drug Delivery Ther., 2, 142 (2012)

[11] Chae YB, Kim SY, Kang CY, Park JB, Yakhak Hoeji, 64, 446 (2020)

[12] Shin TH, Ho MJ, Kim SR, Im SH, Kim CH, Lee S, Kang MJ, Choi YW, Int. J. Biol. Macromol., 109, 544 (2018)

[13] Yamada T, Onishi H, Machida Y, Yakugaku Zasshi, 121, 239 (2001)

[14] Wadher KJ, Kakde RB, Umekar MJ, Int. J. Res. Contr. Rel., 1, 9 (2011)

[15] Mughal MA, Iqbal Z, Neau SH, AAPS PharmSciTech, 12, 77 (2011)

[16] Siepmann F, Hoffmann A, Leclercq B, Carlin B, Siepmann J, J. Control. Release, 119, 182 (2007)

[17] Siepmann F, Siepmann J, WaltherM, MacRae RJ, Bodmeier R, J. Control. Release, 125, 1 (2008)

[18] Nerdy N, J. Penelitian Kimia, 14, 164 (2018)

[19] Fontannaz P, Kilinc T, Heudi O, Food Chem., 94, 626 (2006)

[20] Xie F, Ji S, Cheng Z, Eur. J. Pharm. Sci., 66, 163 (2015)

[21] Shoaib MH, Tazeen J, Merchant HA, Yousuf RI, Pak. J. Pharm. Sci., 19, 119 (2006)

[22] Padayatty SJ, Levine MN, Can. Med. Assoc. J., 164, 353 (2001)

[23] Wechtersbach L, Cigić B, J. Biochem. Biophys. Methods., 70, 767 (2007)

[24] Klimczak I, Gliszczyńska-Świgło A, Food Chem., 175, 100 (2015)

[25] Sung KC, Nixon PR, Skoug JW, Ju TR, Gao P, Topp EM, Patel MV, Int. J. Pharm., 142, 53 (1996)

[26] Bourne DW, Banker GS, Rhodes CT, Principles of Drug Absorption. Modern Pharmaceutics; CRC Press: Florida, pp 67-92, 2002.

[27] Dash S, Murthy PN, Nath L, Chowdhury P, Acta Pol. Pharm., 67, 217 (2010)

[28] Singhvi G, Singh M, Int. J. Pharm. Stud. Res., 2, 77 (2011)

[29] Kiortsis S, Kachrimanis K, Broussali T, Malamataris S, Eur. J. Pharm. Biopharm., 59, 73 (2005)

[30] Jeong KH, Woo HS, Kim CJ, Lee KH, Jeon JY, Lee SY, Kang JH, Lee S, Choi YW, Int. J. Pharm., 495, 1 (2015)