Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
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Evaluation of Physical Properties as Magnesium Stearate Blendedin Hydrophilic Matrix Tablets

  • Choi, Du-Hyung (College of Pharmacy, Pusan National University) ;
  • Jung, Youn-Jung (College of Pharmacy, Pusan National University) ;
  • Wang, Hun-Sik (Center for nanotechnology-based new drug dosage form, College of Pharmacy, Chungnam National University) ;
  • Yoon, Jeong-Hyun (College of Pharmacy, Pusan National University) ;
  • Jeong, Seong-Hoon (College of Pharmacy, Pusan National University)
  • Received : 2011.03.16
  • Accepted : 2011.04.04
  • Published : 2011.04.20
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Abstract

Main objectives of this study were to investigate the effects of a lubricant, magnesium stearate, as blended in a hydrophilic matrix tablet and to identify significant factors using a tablet ejection force and a swelling property. The characteristics of tablet ejection were evaluated with three different compression forces (30, 40, and 60 MPa) and two controlled factors, amount of magnesium stearate and its mixing time. A hydrophilic model drug (terazosin HCl dihydrate) was regarded as a default factor. Tablet swelling was also evaluated. The optimal amount of PEG compared to PEO was set to be 88.50% w/w. As the amount of magnesium stearate was varied from 0.79% to 2.20% w/w, the amount of PEO and PEG was adjusted to meet the tablet's total weight while maintaining the ratio between the two excipients constant. As the mixing time of magnesium stearate was increased, the tablet ejection force and the swelling property were decreased. As the amount of magnesium stearate was increased, the tablet ejection force and the swelling property were decreased since the increased mixing time and the amount of magnesium stearate induced hydrophobic properties of the matrix tablet more effectively. The ejection force of the tablet increased as a result of increase in the compression force, which means that the breaking of tablet/die-wall adhesion energy was also increased when the compression energy was increased. The results gavea valuable guide how to choose suitable amount of the lubricant with processing conditions for the development of hydrophilic matrix formulations.

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References

  1. Alderman, D.A., 1984. A review of cellulose ethers in hydrophilic matrices for oral controlled release dosage forms. Int. J. Pharm.5, 1-9.
  2. Anuar, M.S., Briscoe, B.J., 2009. The elastic relaxation of starch tablets during ejection. Powder Technology. 195, 96-104. https://doi.org/10.1016/j.powtec.2009.05.019
  3. Asker, A., El-Nakeeb, M., Motawi, M., El-Gindy, N., 1973. Effect of certain tablet formulation factors on the antimicrobial activity of tetracycline hydrochloride and chloramphemicol. Pharmazie. 28, 476-478.
  4. Bolhuis, G.K., Jong, S.W., Lerk, C.F., 1987. The effect of magnesium stearate admixing in different types of laboratory and industrial mixers on tablet crushing strength. Drug Dev. Ind. Pharm. 13, 1547-1567. https://doi.org/10.3109/03639048709068680
  5. Campos-Aldrete, M.E., Villafuerte-Robles, L., 1997. Influence of the viscosity degree and the particle size of HPMC on metronidazole release from matrix tablets. Eur. J. Pharm. Biopharm.43, 173-178. https://doi.org/10.1016/S0939-6411(96)00004-5
  6. Conti, S., Maggi, L., Segale, L., Ochoa Machiste, E., Conte, U., Grenier, P., Vergnault, G., 2007. Matrices containing NaCMC and HPMC 2. Swelling and release mechanismstudies. Int. J. Pharm. 333, 143-151. https://doi.org/10.1016/j.ijpharm.2006.11.067
  7. Dansereau, R., Peck, G.E., 1987. The effect of the variability in the physical and chemical properties of magnesium stearate on the properties of compressed tablets.Drug Dev. Ind. Pharm. 13 975-999. https://doi.org/10.3109/03639048709068365
  8. Ebube, N.K., Jones, A.B., 2004. Sustained release of acetaminophen from heterogeneous mixture of two hydrophilic non-ionic cellulose ether polymers. Int. J. Pharm. 272, 19-27. https://doi.org/10.1016/j.ijpharm.2003.11.020
  9. Ford, J.L., Mitchell, K., Rowe, P., Armstrong, D.J., Elliott, P.N.C.,Rostron, C., Hogan, J.E. 1991. Mathematical modeling of drug release from hydroxypropylmethylcellulose matrices: effect of temperature. Int. J. Pharm.71, 95-104. https://doi.org/10.1016/0378-5173(91)90071-U
  10. Gao, P., Skoug, J.W., Nixon, P.R., Ju, T.R., Stemm, N.L., Sung, K.C., 1996. Swelling of hydroxypropylmethylcellulose matrix tablets. Mechanistic study of the influence of formulation variables on matrix performance and drug release.J. Pharm. Sci.85, 732-740. https://doi.org/10.1021/js9504595
  11. Iranloye, T., Parrott, E., 1978. Effects of compression force, particle size, and lubricants on dissolution rate. J. Pharm. Sci. 67, 535-539. https://doi.org/10.1002/jps.2600670424
  12. Johannson, M.E., Nicklasson, M., 1986. Investigation of the film formation of magnesium stearate by applying a flow-through dissolution technique. J. Pharm. Pharmacol. 38, 51-54. https://doi.org/10.1111/j.2042-7158.1986.tb04466.x
  13. Jentgen, R.L., 1971. Solid lubricants. How they work and where to use them. I.E.E.E. Trans. Parts Hybrids Packag., 7, 86-93. https://doi.org/10.1109/TPHP.1971.1136418
  14. Juarez, H., Rico, G., Villafuerte, L., 2001. Influence of admixed carboxymethylcelluloseon release of 4-aminopyridine from hydroxypropylmethylcellulose matrix tablets. Int. J. Pharm. 216, 115-125. https://doi.org/10.1016/S0378-5173(01)00583-X
  15. Kikuta, J., Kitamori, N., 1994. Effect of mixing time on the lubrication properties of magnesium stearate and the final characteristics of the compressed tablets. Drug Dev. Ind. Pharm. 20, 343-355. https://doi.org/10.3109/03639049409050187
  16. Korsmeyer, R.W., Gurny, R., Doelker, E., Buri, P. Peppas, N.A., 1983. Mechanism of solute release from porous hydrophilic polymers. Int. J. Pharm. 15, 25-35. https://doi.org/10.1016/0378-5173(83)90064-9
  17. Lachman, L., Lieberman, H.A., Kanig, J.L., 1970. In Theory and Practice of Industrial Pharmacy. Lea and Febiger, New York, 2nd edn.
  18. Madhusudan Rao, Y., Krishna Veni, J., Jayasagar, G., 2001. Formulationandevaluation of dichlorofenac sodium using hydrophilic matrices. Drug. Dev. Ind. Pharm. 27, 759-766. https://doi.org/10.1081/DDC-100107239
  19. Marshall, K., 1976. Compression and consolidation of Industrial Pharmacy; Lachman, L., Liberman, A., Kanig, J.L., Eds.; Varghese: Bombay, India, 66-99.
  20. Mitchell, K., Ford, J.L., Armstrong, D.J., Elliott, P.N.C., Rostron, C., Hogan, J.E., 1993. The influence of concentration on the release of drugs from gel and matrices containing Methocel. Int. J. Pharm.100, 155-163. https://doi.org/10.1016/0378-5173(93)90086-U
  21. Neau, S.H., Howard, M.A., Claudius, J.S., Howard, D.R., 1999. The effect ofaqueous solubilityof xanthine derivates on the release mechanism fromethylcellulose matrix tablets.Int. J. Pharm. 179, 97-105. https://doi.org/10.1016/S0378-5173(98)00391-3
  22. Nerurkar, J., Jun, H.W., Price, J.C., Park, M.O., 2005. Controlled release matrixtablet of ibuprofen using cellulose ethers and carrageenans: effect of formulationfactors on dissolution rate. Eur. J. Pharm. Biopharm. 61, 56-68. https://doi.org/10.1016/j.ejpb.2005.03.003
  23. Park, J.S., Shim, J.Y., Truong, N.K.V., Park, J.S., Shin, S., Choi, Y.W., Lee, J., Yoon, J.H., Jeong, S.H., 2010. A pharma-robust design method to investigate the effect of PEG and PEO on matrix tablets. Int. J. Pharm. 393, 79-87.
  24. Peter, D., 2004. Oral Solid Dosage Forms, Pharmaceutical preformulationand formulation, Mark Gibson (Eds), Interpharm/CRC, Florida, U.S.A. 386-388.
  25. Podczeck, F., Miah, Y., 1994. The influence of particle size and shape on the angle of internal friction and the flow factor of unlubricated and lubricated powders. Int. J. Pharm., 144, 187-194.
  26. Rao, K.V.R., Devi, K.P., Buri, P. 1990. Influence of molecular size and water solubility of the solute on its release from swelling and erosion controlled polymeric matrices. J. Control. Release 12, 133-141. https://doi.org/10.1016/0168-3659(90)90089-C
  27. Sabir, A., Evans, B., Jain, S., 2001. Formulation and process optimixationto eliminate pocking from market image tablets. Int. J. Pharm. 215, 123-135. https://doi.org/10.1016/S0378-5173(00)00684-0
  28. Sako, K., Nakashima, H., Sawada, T., Fukui, M., 1996. Relationshipbetween gelation rate of controlled-release acetaminophen tablets containing polyethylene oxide and colonic drug release in dogs. Pharm. Res. 13, 594-598. https://doi.org/10.1023/A:1016006423601
  29. Shah, A.C., Mlodozeniec, A.R., 1977.Mchanism of surface lubrication : Influence of duration of lubricant-excipient mixing on processing characteristics of powders and properties of compressed tablets. J. Pharm. Sci. 66, 1377-1382. https://doi.org/10.1002/jps.2600661006
  30. Sheskey, P.J., Robb, R.T., Moore, R.D., Boyce, B.M., 1995. Effect of lubricant level, method of mixing, and duration of mixing on a controlled-release matrix tablet containing hydroxypropyl methylcellulose. Drug Dev. Ind. Pharm. 21, 2151-2165. https://doi.org/10.3109/03639049509065898
  31. Sprowl, Sprowl’s 1974. American Pharmacy. 7th edn. J.B. Lippincott,Philadelphia-Toronto, pp. 311-367.
  32. Van der Watt, J.G., 1987. The effect of the particle size of microcrystallinecellulose on tablet properties in mixtures with magnesium stearate. Int. J. Pharm. 36, 51-54. https://doi.org/10.1016/0378-5173(87)90235-3
  33. Yamamura, T., Ohta, T., Taira, T., Ogawa, Y., Sakai, Y., Moribe, K., Yamamoto, K., 2009. Effects of automated external lubrication on tablet properties and the stability of eprazinone hydrochloride. Int. J. Pharm. 370, 1-7. https://doi.org/10.1016/j.ijpharm.2008.11.007