HPMC의 입도에 따른 염산벤라팍신 및 카바마제핀 서방성 정제의 용출 특성

차재욱; 차자현; 홍준기; 이성완; 고원화; 백현호; Jae Uk Cha; Ja Hyun Cha; Jun Kee Hong; Sung Wan Lee; Won Hwa Ko; Hyun Ho Beak

Polymer(Korea), Vol.36, No.3, 332-337, May, 2012

Export Citation

HPMC의 입도에 따른 염산벤라팍신 및 카바마제핀 서방성 정제의 용출 특성

Effect of Particle Size of HPMC on Dissolution Rate of Venlafaxine HCl and Carbamazepine Sustained Release Tablet

차재욱, 차자현, 홍준기, 이성완, 고원화, 백현호^†

삼성정밀화학(주)

Jae Uk Cha, Ja Hyun Cha, Jun Kee Hong, Sung Wan Lee, Won Hwa Ko, and Hyun Ho Beak^†

Samsung Fine Chemicals Co., Ltd., 129B/4L, Namdong Industrial Complex, 696-3, Gojan-dong, Namdong-gu, Incheon 405-820, Korea

E-mail:

초록

본 연구는 약물의 용해도에 따른 서방성 용출 거동의 특성을 파악하기 위해 수행되었으며, 이에 따라 고 분자의 입도에 따른 염산벤라팍신과 카바마제핀의 정제를 제조하였다. 사용된 고분자는 경구를 통한 서방성 약물전달 시스템 설계에 가장 널리 사용되는 히드록시 프로필 메틸셀룰로오스(HPMC)이며, HPMC의 입도 분포에 따른 팽윤 속도의 차이는 중요한 특성으로 약물의 용출에 큰 영향을 미친다. HPMC 입도에 따른 정제 표면을 분석하기 위해 SEM을 사용하였으며, 결정학적 특성을 파악하기 위해 DSC를 이용하여 분석하였고, 용출 특성의 주요 메카니즘을 파악하기 위해 용출 모델식을 적용하였다. 본 연구를 통해 약물의 용해도 및 HPMC의 입도에 따라 약물의 용출 거동을 조절할 수 있었다.

The primary objective of this work is to find the properties of sustained release dissolution pattern depending on solubility of drugs, so venlafaxine HCl and carbamazepine tablets were made by using polymer wich various particle size. Hydroxy propyl methyl cellulose (HPMC) has been utilized in this study as an excipient that is one of the most widely used polymers for an oral sustained release formulation, and drug release pattern was strongly influenced by swelling rate depending on particle size of HPMC. Scanning electron microscope (SEM) was employed to investigate the surface of tablets with various HPMC particle size, and differential scanning calorimeter (DSC) was employed to investigate the crystallization of drugs in tablets. The release model equation was applied to analyze the main mechanism of drug release pattern. The results demonstrate that drug release pattern is controlled by the drug solubility and HPMC particle size.

Keywords:HPMC;sustained release;venlafaxine HCl;carbamazepine;AnyCoat-C.

[References]

Jeong SC, Chon SK, Jo YH, Kim MS, Lee B, Khang G, Lee HB, Polym.(Korea), 29(3), 288 (2005)
Ford JL, Rubinstein MH, McCaul F, Hogan JE, Edgar PJ, Inter. J. Pharm., 40, 223 (1987)
Siepmann J, Kranz H, Bodmeier R, Peppas NA, Pharmaceut. Res., 16, 1748 (1999)
Chiwele I, Johes BE, Podczeck F, Chem. Pharm. Bull., 48, 951 (2000)
Kim W, Song BJ, Kim DS, Kim SJ, Lee SK, Kim HL, Lee D, Khang G, Polym.(Korea), 34(3), 269 (2010)
Velasco MV, Ford JL, Rowe P, Siahboomi AR, J.Control. Release., 57, 75 (1999)
Yu LX, Amidon GL, Polli JE, Zhao H, Mehta MU, Conner DP, Shah VP, Lesko LJ, Chen ML, Lee VHL, Hussain AS, Pharm. Res., 19, 921 (2002)
Lindenberg M, Kopp S, Dressman JB, Eur. J. Pharm.Biopharm., 58, 265 (2004)
Jamzad S, Fassihi R, Inter. J. Pharm., 312, 24 (2006)
Turner S, Federici C, Hite M, Fassihi R, Drug Dev.Ind. Pharm., 30, 797 (2004)
Tournel G, Houdret N, Hedouin V, Deveaux M, Gosset D, Lhermitte M, J. Chromatography B., 761, 147 (2001)
Makhija SN, Vavia PR, J. Pharm. Biomed. Anal., 28, 1055 (2002)
Matoga M, Pehourcq F, Titier K, Dumora F, Jarry C, J. Chromatography B., 760, 213 (2001)
Singh G, Ghosh B, Kaushalkumar D, Somsekhar V, AAPS Pharm. Sci. Tech., 9, 791 (2008)
Jin LY, Zhang Y, Ma NN, Sun YH, Jiao CM, Li SM, Chin. J. Pharm., 6, 116 (2008)
Kim JY, Kim HT, Kim CK, J. Kor. Pharm. Sci., 38, 335 (2008)
Mandal S, Mandal SD, J. Pharm. Sci. Rev. Res., 3, 56 (2010)
Kratz JM, Teixeira MR, Koester LS, Simoes CMO, Brajilian J. Med. Biol. Res., 44, 531 (2011)
Ford JL, Rubinstein MH, Hogan JE, Inter. J.Pharm., 24, 327 (1985)
U. S. Pharmacopeia National Formulary., The United States Pharmacopeial Convention, 34, 4572 (2011)
U. S. Pharmacopeia National Formulary., The United States Pharmacopeial Convention, 34, 2158 (2011)
Kabir AK, Jesmeen T, Jahangir R, Rahman M, Rouf ASS, Stamford J. Pharm. Sci., 1, 51 (2008)
Singh SK, Pandit JK, Mishra DN, Acta Pharm. Sinica., 48, 167 (2006)
Mura P, Fauucci MT, Manderioli A, Bramanti G, Ceccarelli L, J. Pharm. Biomed., 18, 151 (1998)
Aboelwafa AA, Basalious EB, AAPS Pharm. Sci.Tech., 11, 1026 (2010)
Otsuka M, Hasekawa H, Matsuda Y, Chem. Pharm. Bull., 47, 852 (1999)

[1] Jeong SC, Chon SK, Jo YH, Kim MS, Lee B, Khang G, Lee HB, Polym.(Korea), 29(3), 288 (2005)

[2] Ford JL, Rubinstein MH, McCaul F, Hogan JE, Edgar PJ, Inter. J. Pharm., 40, 223 (1987)

[3] Siepmann J, Kranz H, Bodmeier R, Peppas NA, Pharmaceut. Res., 16, 1748 (1999)

[4] Chiwele I, Johes BE, Podczeck F, Chem. Pharm. Bull., 48, 951 (2000)

[5] Kim W, Song BJ, Kim DS, Kim SJ, Lee SK, Kim HL, Lee D, Khang G, Polym.(Korea), 34(3), 269 (2010)

[6] Velasco MV, Ford JL, Rowe P, Siahboomi AR, J.Control. Release., 57, 75 (1999)

[7] Yu LX, Amidon GL, Polli JE, Zhao H, Mehta MU, Conner DP, Shah VP, Lesko LJ, Chen ML, Lee VHL, Hussain AS, Pharm. Res., 19, 921 (2002)

[8] Lindenberg M, Kopp S, Dressman JB, Eur. J. Pharm.Biopharm., 58, 265 (2004)

[9] Jamzad S, Fassihi R, Inter. J. Pharm., 312, 24 (2006)

[10] Turner S, Federici C, Hite M, Fassihi R, Drug Dev.Ind. Pharm., 30, 797 (2004)

[11] Tournel G, Houdret N, Hedouin V, Deveaux M, Gosset D, Lhermitte M, J. Chromatography B., 761, 147 (2001)

[12] Makhija SN, Vavia PR, J. Pharm. Biomed. Anal., 28, 1055 (2002)

[13] Matoga M, Pehourcq F, Titier K, Dumora F, Jarry C, J. Chromatography B., 760, 213 (2001)

[14] Singh G, Ghosh B, Kaushalkumar D, Somsekhar V, AAPS Pharm. Sci. Tech., 9, 791 (2008)

[15] Jin LY, Zhang Y, Ma NN, Sun YH, Jiao CM, Li SM, Chin. J. Pharm., 6, 116 (2008)

[16] Kim JY, Kim HT, Kim CK, J. Kor. Pharm. Sci., 38, 335 (2008)

[17] Mandal S, Mandal SD, J. Pharm. Sci. Rev. Res., 3, 56 (2010)

[18] Kratz JM, Teixeira MR, Koester LS, Simoes CMO, Brajilian J. Med. Biol. Res., 44, 531 (2011)

[19] Ford JL, Rubinstein MH, Hogan JE, Inter. J.Pharm., 24, 327 (1985)

[20] U. S. Pharmacopeia National Formulary., The United States Pharmacopeial Convention, 34, 4572 (2011)

[21] U. S. Pharmacopeia National Formulary., The United States Pharmacopeial Convention, 34, 2158 (2011)

[22] Kabir AK, Jesmeen T, Jahangir R, Rahman M, Rouf ASS, Stamford J. Pharm. Sci., 1, 51 (2008)

[23] Singh SK, Pandit JK, Mishra DN, Acta Pharm. Sinica., 48, 167 (2006)

[24] Mura P, Fauucci MT, Manderioli A, Bramanti G, Ceccarelli L, J. Pharm. Biomed., 18, 151 (1998)

[25] Aboelwafa AA, Basalious EB, AAPS Pharm. Sci.Tech., 11, 1026 (2010)

[26] Otsuka M, Hasekawa H, Matsuda Y, Chem. Pharm. Bull., 47, 852 (1999)