화학공학소재연구정보센터
Journal of the Korean Industrial and Engineering Chemistry, Vol.10, No.2, 201-205, April, 1999
Hydroxypropylmethylcellulose로부터 염산슈도에페드린의 방출조절에 관한 연구
A Study on the Control of Pseudoephedrine Hydrochloride Release from Hydroxypropylmethylcellulose Matrices
초록
Hydroxypropylmethylcelluloses (HPMC)는 친수성 cellulose 계통의 중합체로서 독성이 적고 가격이 저렴하여 경구용 서방출성 제제에 널리 이용되고 있다. 본 연구에서는 매트릭스로서 HPMC를 이용하여 새로운 서방출성제제인 HPMC/염산슈도에페드린계를 설계하고, 직타법에 의하여 정제를 제조하였으며, 이 팽윤될 수 있는 친수성 약물전달계를 이용하여 약물의 방출에 영향을 주는 여러 인자들이 약물의 방출속도에 미치는 영향에 대하여 조사하였다. 결과로서, HPMC/염산슈도에페드린계에서 매트릭스인 HPMC의 분자량이 클수록, HPMC의 함량이 많을수록 약물의 방출속도가 더 느려짐을 알 수 있었으며, 정제의 경도나 용출시 pH 변화에는 무관한 것으로 나타났다. 특히, 음이온 계면활성제인 sodium laurylsulfate 는 HPMC로부터 염산 슈도에페드린의 방출속도를 지연시키는데 큰 영향을 미치는 것으로 나타났으며, 이러한 현상은 음이온 계면활성제인 sodium laurylsulfate가 반대의 이온성을 갖는 약물인 염산슈도에페드린과 착물을 형성함으로써 약물의 용해성이 떨어져서 약물방출이 지연되는 것으로 생각된다.
Hydroxypropylmethylcelluloses (HPMC) are cellulose ethers which may be used as the basis for hydrophilic matrices for controlled release oral delivery and offer the advantages of being non-toxic and relatively inexpensive. In this work, we designed new drug release system using HPMC as matrix, manufactured by direct compression technology and have investigated the effects of the controlling factors on drug release from a swellable hydrophillic delivery system. It was found that the release rate of the drug decreased with increasing the polymer molecular weight and the polymer content in tablets, and was independent of compaction pressure and pH of dissolution fluids. Especially, the ability of the anionic surfactant, sodium laurylsulfate, to retard the release of pseudoephedrine hydrochloride from HPMC was characterised. With increasing the concentration of the sodium laurysulfate within the matrix, drug release rate decreased. It is believed that, provided the pseudoephedrine hydrochloride and the sodium laurysulfate are oppositely charged, they will bind together in situ within the HPMC matrix, leading to reduced drug release rates.
  1. Christensen GL, Dale LB, U.S. Patent, 3,065,143 (1962)
  2. Lapidus H, Lordi NG, J. Pharm. Sci., 55, 840 (1966) 
  3. Lapidus H, Lordi NG, J. Pharm. Sci., 57, 1292 (1968) 
  4. Alderman DA, Int. J. Pharm. Technol. Prod. Manufac., 5, 1 (1984)
  5. Ford JL, Rubinstein MH, Hogan JE, Int. J. Pharm., 24, 327 (1985) 
  6. Ford JL, Rubinstein MH, Hogan JE, Int. J. Pharm., 24, 339 (1985) 
  7. Ford JL, Rubinstein MH, McCaul F, Hogan JE, Edgar PJ, Int. J. Pharm., 40, 223 (1987) 
  8. Hogan JE, Drug Development Ind. Pharmacy, 15, 975 (1989)
  9. Feely LC, Davis SS, Int. J. Pharm., 41, 83 (1988) 
  10. Feely LC, Davis SS, Int. J. Pharm., 44, 131 (1988) 
  11. Ford JL, Mitchell K, Sawh D, Ramdour S, Armstrong DJ, Rostron C, Hogan JE, Int. J. Pharm., 71, 213 (1991) 
  12. Huber HE, Dale LB, Christensen GL, J. Pharm. Sci., 55, 974 (1966) 
  13. Pentel P, JAMA, 252, 809 (1984)
  14. Burgot G, Burgot JL, Ann. Pharm. Fr., 44, 313 (1986)
  15. Kanfer I, Dowse R, Vuma V, Pharmacotherapy, 13, 116S (1993)
  16. Conell JT, Gold AJ, Zola EM, Paule CL, Drug Int. Clin. Pharm., 18, 244 (1984)
  17. Graves DA, Rotenberg KS, Woodworth JR, Amsel LP, Hinsvark ON, Clin. Pharm., 4, 199 (1985)
  18. Voegele D, Brockmeier D, Hattingberg HM, Lippold BC, Acta Pharm. Technol., 29, 167 (1983)
  19. Kim H, Reza F, J. Pharm. Sci., 86, 323 (1997) 
  20. Lee PI, Pepas NA, J. Control. Release, 6, 207 (1987) 
  21. Ju TCR, Nixon PR, Patel MV, J. Pharm. Sci., 84, 1455 (1995) 
  22. Ju TCR, Nixon PR, Patel MV, J. Pharm. Sci., 84, 1464 (1995) 
  23. Rajabi-Siahboomi AR, Bowtell RW, Mansfield P, Henderson A, Davies MC, Media CD, J. Control. Release, 31, 121 (1994)