발기부전과 고혈압을 치료하기 위한 이중층 타다라필 및 암로디핀 복합 정제 제조

신은영; 박종호; 신명은; 송정은; 강길선; Eun Yeong Shin; Jong Ho Park; Myeong Eun Shin; Jeong Eun Song; Gilson Khang

Polymer(Korea), Vol.43, No.2, 274-281, March, 2019

DOI10.7317/pk.2019.43.2.274 Export Citation

발기부전과 고혈압을 치료하기 위한 이중층 타다라필 및 암로디핀 복합 정제 제조

Formulation of Double-layer Tadalafil and Amlodipine Complex Tablets to Treat Erectile Dysfunction and Hypertension

신은영, 박종호, 신명은, 송정은, 강길선^†

전북대학교 BIN 융합 공학과

Eun Yeong Shin, Jong Ho Park, Myeong Eun Shin, Jeong Eun Song, and Gilson Khang^†

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

E-mail:

초록

40세 이상의 많은 남성들은 여러 가지 이유로 발기부전(erectile dysfunction, ED)의 고통을 가지고 있다. 또한 ED 환자의 40% 이상이 고혈압 질환을 동시에 가진다. 타다라필(tadalafil, TD)은 선택적이고, 가역적인 cGMP- 특이적 PDE-5억제제이다. 이는 생물 약제 분류 시스템 클래스-II의 불용성 약물로, 가용화제로 습식 과립제로 제조되었다. 암로디핀 베실레이트(amlodipine besylate, AM)는 수축기 고혈압 및 뇌졸중 예방에 효과적인 칼슘 채널 길항제이며, 물리적 혼합 방법을 사용하여 제조하였다. TD와 AM을 2중층 복합정제로 제작하여 사용하였고, 이는 동시에 두 가지 질병을 예방하거나 치료가능하다. 주사 전자 현미경(SEM), 푸리에 변환 적외선 분광법(FTIR), 시차 주사 열량계(DSC), X선 회절(XRD)은 화학적 및 물리적 특성평가를 위해 실시하였다. 또한 생체외 용출 테스트는 pH=1.2에서 정제의 용출률을 평가하기 위해 실시하였다. 결론적으로, 이중층 정제에서 두 가지 약물의 빠른 방출을 확인하였고, 따라서 이는 약학적 치료제로서 적용될 수 있다.

Many men over the age of 40 suffer from erectile dysfunction (ED) for a variety of reasons. In addition, more than 40% of ED patients have hypertensive disease at the same time. Tadalafil (TD) is a selective and reversible inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase type 5 (cGMP-specific PDE-5). It is an insoluble drug with biopharmaceutics classification system class-II and was prepared by wet granulation with a solubilizing agent. Amlodipine besylate (AM) is a calcium channel antagonist that is effective in preventing systolic hypertension and stroke, and is manufactured using physical mix method. We used TD and AM to fabricate a double-layer complex tablet that can prevent or treat two diseases at the same time. Scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC), X-ray diffraction (XRD) were analyzed for confirming chemical and physical characterization. Also, in vitro dissolution test was conducted to evaluate the dissolution rate of tablet at pH=1.2. In conclusion, the rapid release of two drugs in the double layer tablet was confirmed and could be applied as a pharmaceutical therapeutic agent.

Keywords:tadalafil;amlodipine besylate;double-layer tablet;erectile dysfunction;hypertension

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[1] Nicolosi A, Moreira ED, Villa M, Glasser DB, J. Affect. Disord., 82, 235 (2004)

[2] Smith AD, Urol. Clin. North. Am., 15, 41 (1988)

[3] Inman BA, Sauver JL, Jacobson DJ, McGree ME, Nehra A, Lieber MM, Roger VL, Jacobsen SJ, Mayo. Clin. Proc., 84, 108 (2009)

[4] Esposito K, Giugliano F, Palo CD, Giugliano G, Marfella R, Andrea F, Armiento M, Giugliano D, Jama-J Am. Med. Assoc., 291, 2978 (2004)

[5] Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP, Mckinlay JB, J. Urol., 163, 460 (2000)

[6] Rosen RC, Urol. Clin. North. Am., 28, 269 (2001)

[7] Hatch JP, Delapena AM, Fisher JG, J. Urol., 138, 781 (1987)

[8] Heaton JPW, Adams MA, Endocrine, 23, 119 (2004)

[9] Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA, Jama-J. Am. Med. Assoc., 294, 2996 (2005)

[10] Burchardt M, Burchardt T, Baer L, Kiss AJ, Pawar RV, Shabsigh A, de la Taille A, Hayek OR, Shabsigh R, J. Urol., 164, 1188 (2000)

[11] Giuliano FA, Leriche A, Jaudinot EO, de Gendre AS, Urology, 64, 1196 (2004)

[12] Augustyniak RA, Tuncel M, Zhang W, Toto RD, Victor RG, J. Hypertens., 20, 3 (2002)

[13] Esler M, Eikelis N, Schlaich M, Lambert G, Alvarenga M, et al., Clin. Exp. Pharmacol. Pharmacol., 35, 498 (2008)

[14] Okunlola A, Front. Pharmacol., 5, 294 (2015)

[15] Vaithiyalingam SR, Sayeed VA, Int. J. Pharmaceut., 398, 9 (2010)

[16] Eardley I, Cartledge J, Int. J. Clin. Pract., 56, 300 (2002)

[17] de Tejada IS, Anglin G, Knight JR, Emmick JT, Diabetes Care, 25, 2159 (2002)

[18] Gresser U, Gleiter CH, Eur. J. Med. Res., 7, 435 (2002)

[19] Vuddanda PR, Montenegro-Nicolini M, Morales JO, Velaga S, Eur. J. Pharm. Sci., 109, 372 (2017)

[20] Meredith PA, Elliott HL, Clin. Pharmacokinet., 22, 22 (1992)

[21] Morgan JL, Kogutt BK, Meek C, Stehel EK, Mclntire DD, Sheffield JS, Roberts SW, Pregnancy Hypertens, 11, 77 (2018)

[22] Rad RT, Mortazavi SA, Vatanara A, Dadashzadeh S, Iran. J. Pharm. Res., 16, 1335 (2017)

[23] Mubtasim N, Kabir ER, Podder AK, Bhadra S, Saudi. Pharm. J., 24, 689 (2016)

[24] Chowdary KPR, Rao AS, Asian J. Chem., 20, 4581 (2008)