습식 과립을 통해 용해도가 개선된 나프록센 나트륨 제형 설계

이성원; 조훈휘; 김진우; 김남영; 김필윤; 송철의; 이원찬; 최정민; 송정은; 강길선; Seong Won Lee; Hun Hwi Cho; Jin Woo Kim; Nam Yeong Kim; Pil Yun Kim; Cheol Ui Song; Won Chan Lee; Jeong Min Choi; Jeong Eun Song; Gilson Khang

Polymer(Korea), Vol.45, No.3, 346-352, May, 2021

DOI10.7317/pk.2021.45.3.346 Export Citation

습식 과립을 통해 용해도가 개선된 나프록센 나트륨 제형 설계

Design of Naproxen Sodium Formulations with Improved Solubility by Wet Granulation

이성원, 조훈휘, 김진우, 김남영, 김필윤, 송철의, 이원찬, 최정민, 송정은 , 강길선 ^†

전북대학교 바이오나노융합공학과, 고분자나노공학과, 고분자융합소재연구소

Seong Won Lee, Hun Hwi Cho, Jin Woo Kim, Nam Yeong Kim, Pil Yun Kim, Cheol Ui Song, Won Chan Lee, Jeong Min Choi, Jeong Eun Song , and Gilson Khang^†

Department of Bionanotechnology and Bio-Convergence Engineering, Department of PolymerNano Science & Technology and Polymer Materials Fusion Research Center, Chonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea

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초록

최근 유전 및 노화로 인해 관절염(류마티스, 퇴행성 관절염 등)으로 고통받는 환자들이 증가하고 있으며, 이들 대부분의 환자들은 지속적인 통증으로 인해 건강 관련 삶의 질(HQRL)이 저하되고 있다. 통증 치료를 위해서는 비스테로이드성 항염증제(NSAIDs)가 널리 사용되고 있으며, 대표적인 치료제로 나프록센 나트륨(NAP)이 사용된다. NAP는 발열, 염증, 통증을 일으키는 프로스타글란딘(PG)의 생성에 관여하는 효소인 사이클로옥시게나제 1과 2(COX-1, COX-2)를 억제하는 장점이 있으며, 상대적으로 반감기가 12시간이다. 그러나 NAP는 하루에 2번 275-550 mg 의 경구 투여에 의해 용해도가 낮고 흡수도가 높은 생물약제학적 분류체계 class 2 약물이다. 나프록센 나트륨의 낮은 용해도를 개선하기 위해 수용성 고분자인 폴리비닐피롤리돈(PVP-K30), 폴리비닐알콜(PVA), 전분과 NAP를 습식과립법으로 과립을 제조하였다. 이후 NAP의 향상된 형태와 용해도를 확인하고자 주사전자현미경(SEM), 시차주사 열량분석법(DSC), X선 회절분석법(XRD), 푸리에 변환 적외선 분광학(FTIR) 및 고성능 액체 크로마토그래피(HPLC)를 통해 확인하였다. 이러한 결과를 바탕으로 습식 과립 형성을 통해 NAP의 용해도가 향상되었음을 보여주었고, 즉시 방출 효과인 속방정으로써 관절염에 대한 치료제로 응용 가능하다는 것을 보여주었다.

Recently, many patients are suffered from arthritis including osteoarthritis, rheumatoid arthritis due to increment in genetic disease and aging. Most patients with arthritis have a relatively low health-related quality of life (HRQL) due to persistent pain. For the treatment of pain, non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and among them, naproxen sodium (NAP) is typically applied. NAP has merits in inhibiting cyclooxygenases 1 and 2 (COX- 1, COX-2), enzymes involved in the production of prostaglandin (PG) which cause fever, inflammation, and pain, and has a relatively long half-life of 12 h. However, NAP is a biopharmaceutics classification system (BCS) class 2 drugs with low solubility and high absorption by oral administration of 275~550 mg per time, twice a day. Herein, the low solubility of NAP was improved by wet granulation of the water-soluble polymer polyvinylpyrrolidone (PVP-K30), polyvinyl alcohol (PVA), starch, and NAP. The improved morphology and solubility of NAP was confirmed by scanning electron microscope (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC). Overall results showed enhanced solubility of NAP through the wet granule formation and showed promising treatment for arthritis as immediate release medicinal effects.

Keywords:naproxen sodium;wet granulation;non-steroidal anti-inflammatory drug;rheumatoid arthritis

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Olshavsky MA, Allcock HR, Chem. Mater., 9, 1367 (1997)
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Roth GA, Neu-Baker NM, Brenner SA, Sci. Total Environ., 508, 1 (2015)

[Related Articles]

[1] Wolfe F, King SX, Watson DJ, J. Rheumatol., 27, 1373 (2000)

[2] Dewitt DL, Meade EA, Smith WL, Am. J. Med., 95, 40S (1993)

[3] Vane J, Nature, 367(6460), 215 (1994)

[4] Pairet M, Engelhardt G, Fundam. Clin. Pharmacol., 10, 1 (1996)

[5] Sarkar K, Sadat SMA, Islam MS, Jalil R, Dhaka Univ. J. Pharm. Sci., 10, 123 (2011)

[6] Savaroglu G, Caglar M, Ildaser AC, Hur E, Ilican S, Appl. Surf. Sci., 492, 66 (2019)

[7] Shah SU, Shah KU, Jan SU, Ahamad K, Rehman AU, Hussain A, Khan GM, J. Pharm. Sci., 24, 255 (2011)

[8] Mandal S, Basu SK, Sa B, AAPS PharmSciTech., 10, 1348 (2009)

[9] Martino PD, Malaj L, Censi R, Martelli S, J. Pharm. Sci., 97, 5263 (2008)

[10] Suzuki H, Sunada H, Chem. Pharm. Bull., 46, 482 (1998)

[11] Kirk JH, Dann SE, Blatchford CG, Int. J. Pharm., 334, 103 (2007)

[12] Sharma P, Chawla A, Pawar P, Sci. World J., 2013, 654829 (2013)

[13] Tang B, Wang J, Wang Q, Xiao Y, Huang Y Liao X, Li H, Spectrosc. Lett., 49, 404 (2016)

[14] Omkaram I, Chakradhar RPS, Rao JL, Physica B, 388, 318 (2007)

[15] Olshavsky MA, Allcock HR, Chem. Mater., 9, 1367 (1997)

[16] Goddeeris C, Mooter GVD, Eur. J. Pharm. Sci., 35, 104 (2008)

[17] Chen YX, Liu SY, Wang GY, J. Colloid Interface Sci., 303(2), 380 (2006)

[18] Tan JZ, Balasubramanian BM, J. Food Eng., 212, 146 (2017)

[19] Roth GA, Neu-Baker NM, Brenner SA, Sci. Total Environ., 508, 1 (2015)