Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Effect of Solvents on Physical Properties and Release Characteristics of Monolithic Hydroxypropylmethylcellulose Matrix Granules and Tablets

  • Cao Qing-Ri (National Research Laboratory for Bioavailability Control, College of Pharmacy, Kangwon National University, College of Pharmacy, Yanbian University) ;
  • Choi Yun-Woong (National Research Laboratory for Bioavailability Control, College of Pharmacy, Kangwon National University, Seoul Pharma Co., LTD.) ;
  • Cui Jing-Hao (College of Pharmacy, Yanbian University) ;
  • Lee Beom-Jin (National Research Laboratory for Bioavailability Control, College of Pharmacy, Kangwon National University)
  • Published : 2005.04.01
Download PDF
⟨ Previous Next ⟩

Abstract

Effect of solvents on physical characteristics and release characteristics of monolithic acetaminophen (APAP) hydroxypropylmethylcellulose (HPMC) matrix granules and tablets were examined. Various types and amounts of solvents were employed for granulation and coating. APAP and other excipients were mixed and were then wet-granulated in a high-speed mixer. The dried granules were then directly compressed and film-coated with low viscosity grade HPMC. As the amount of water increased, the size of granules also increased, showing more spherical and regular shape. However, manufacturing problems such as capping and lamination in tableting occurred when water was used alone as a granulating solvent. The physical properties of HPMC matrix granules were not affected by the batch size. The initial release rate as well as the amount of APAP dissolved had a tendency to decrease as the water level increased. Addition of nonaqueous solvent like ethanol to water resulted in good physical properties of granules. When compared to water/ethanol as a coating solvent, the release rate of film-coated HPMC matrix tablets was more sensitive to the conditions of coating and drying in methylene chloride/ethanol. Most of all, monolithic HPMC matrix tablet when granulated in ethanol/water showed dual release with about $50\%$ drug release immediately within few minutes followed by extended release. It was evident that the type and amount of solvents (mainly water and ethanol) were very important for wet granulation and film-coating of monolithic HPMC matrix tablet, because the plastic deforming and fragmenting properties of material were changed by the different strengths of the different solvents.

Keywords

References

  1. Anaebonam, A. O., Clemente, E., and Mendes, R. W., Extended release acetaminophen, United States Patent: 6,254,891; July 3, (2001)
  2. Cao, Q. R., Choi, H. G., Kim, D. C., and Lee, B. J., Release behavior and photo-image of nifedipine tablet coated with high viscosity grade hydroxypropylmethylcellulose: effect of coating conditions. Int. J. Pharm., 274, 107-117 (2004) https://doi.org/10.1016/j.ijpharm.2004.01.020
  3. Chowhan, Z. T. and Palagyi, L., Hardness increase induced by partial moisture loss in compressed tablets and its effect on in vitro dissolution. J. Pharm. Sci., 67, 1385-1389 (1978) https://doi.org/10.1002/jps.2600671014
  4. Ebube, N. K., Hikal, A. H., Wyandt, C. M., Beer, D. C., Miller L. G., and Jones, A. B., Sustained release of acetaminophen from heterogeneous matrix tablet: Influence of polymer ratio, polymer loading and co-active on drug release. Pharm. Dev.Technol., 2, 161-170 (1997a) https://doi.org/10.3109/10837459709022621
  5. Ebube, N. K., Hikal, A. H., Wyandt, C. M., Beer, D. C., Miller L. G., and Jones, A. B., Effect of drug, formulation and process variables on granulation and compaction characteristics of heterogeneous matrices. Part 1: HPMC and HPC systems, Int. J. Pharm., 156, 49-57 (1997b) https://doi.org/10.1016/S0378-5173(97)00180-4
  6. Farag Badawy, S. I., Menning, M. M., Gorko, M. A., and Gilbert, D. L., Effect of process parameters on compressibility of granulation manufactured in a high-shear mixer. Int. J. Pharm., 198, 51-61 (2000) https://doi.org/10.1016/S0378-5173(99)00445-7
  7. Ford, J. L., Rubinstein, M. H., and Hoagen, J. E., Formulation of sustained release promethazine hydrochloride tablets using hydroxypropylmethylcellulose matrices. Int. J. Pharm., 24, 327-338 (1985) https://doi.org/10.1016/0378-5173(85)90031-6
  8. Freely, L. C. and Davis, S. S., Influence of polymeric excipients on drug release from hydroxypropylmethylcellulose matrices. Int. J. Pharm., 44, 131-139 (1988) https://doi.org/10.1016/0378-5173(88)90109-3
  9. Henz, R., Wolf, H., Schuchmann, H., End, L., and Kolter K., Formulation and development of tablets based on ludipress and scale-up from laboratory to production scale. Drug Dev. Ind. Pharm., 26, 513-521 (2000) https://doi.org/10.1081/DDC-100101262
  10. Kristensen, H. G., Agglomeration of powders. Act. Pharm. Suec., 25, 187-204 (1988)
  11. Landin, M., York, P., Cliff, M. J., Rowe, R. C., and Wigmore, A. J., The effect of batch size on scale-up of a pharmaceutical granulation in a fixed bowl mixer granulator. Int. J. Pharm., 134, 243-246 (1996) https://doi.org/10.1016/0378-5173(96)04461-4
  12. Lee, B. J., Ryu, S. G., and Cui, J. H., Controlled release of dual drug-loaded hydroxypropylmethylcellulose matrix tablet using drug-containing polymeric coatings. Int. J. Pharm., 188, 71-80 (1999a) https://doi.org/10.1016/S0378-5173(99)00204-5
  13. Lee, B. J., Ryu, S. G., and Cui, J. H., Formulation and release characteristics of hydroxypropylmethylcellulose matrix tablet containing melatonin. Drug Dev. Ind. Pharm., 25, 493-501 (1999b) https://doi.org/10.1081/DDC-100102199
  14. Liu, C. H., Chen, S. C., Kao, Y. H., Kao, C. C., Sokoloski, T. D., and Sheu, M. T., Properties of hydroxypropylmethylcellulose granules produced by water-spraying. Int. J. Pharm., 100, 241-248 (1993) https://doi.org/10.1016/0378-5173(93)90097-Y
  15. Maffion, G., Iamartino, P., Guglielmini, G., and Gazzaniga, A., High-viscosity HPMC as a film-coating agent. Drug Dev. Ind. Pharm., 19, 2043-2053 (1993) https://doi.org/10.3109/03639049309069340
  16. McConville, J. T., Ross, A. C., Chambers, A. R., Smith G., Florence, A. J., and Stevens, H. N. E., The effect of wet granulation on the erosion behaviors of an HPMC-lactose tablet, used as a rate-controlling component in a pulsatile drug delivery capsule formulation. Eur. J. Pharm. Biopharm., 57, 541-549 (2004) https://doi.org/10.1016/j.ejpb.2004.01.004
  17. Muti, H. and Othman, S., Effects of binders and moisture content on the disintegration, hardness and friability of paracetamol and orphenadrine citrate tablets. Drug Dev. Int. Pharm., 15, 2017-2035 (19890 https://doi.org/10.3109/03639048909052516
  18. Phadke, D. S. and Anderson N. R., Effect of crospovidone on the wet granulation aspects of acetaminophen. Drug Dev. Ind. Pharm., 16, 983-994 (1990) https://doi.org/10.3109/03639049009114923
  19. Rambali, B., Baert, L., and Massart, D. L., Scaling up of the fluidized bed granulation process. Int. J. Pharm., 252, 197- 206 (2003) https://doi.org/10.1016/S0378-5173(02)00646-4
  20. Shah, S. A. and Ho, C. Y., Immediate release/sustained release compressed tablets, United States Patent: 6,126,969; October 3, (2000)
  21. Shah, N. H., Railkar, A. S., Phauapradit, W., Zeng, F., Chen, A., Infeld, M. H., and Malick, A. W., Effect of processing techniques in controlling the release rate and mechanical strength of hydroxypropylmethylcellulose based hydrogel matrices. Eur. J. Pharm. Biopharm., 42, 183-187 (1996)
  22. Shiraishi, T., Kondo, S., Yuasa, H., and Kanaya, Y., Studies on the granulation process of granules for tableting with a highspeed mixer: I: physical properties of granules for tableting. Chem. Pharm. Bull., 42, 932-936 (1994) https://doi.org/10.1248/cpb.42.932
  23. Walson, P. D., Galletta, G., Braden, N. J., and Alexander, L., Ibuprofen, acetaminophen, and placebo treatement of febrile children. Clin. Pharmacol. Ther., 46, 9-17 (1989) https://doi.org/10.1038/clpt.1989.100
  24. Watano, S., Takashima, H., and Miyanami, K., Scale-up of agitation fluidized bed granulation. V. Effect of moisture content on scale-up characteristics. Chem. Pharm. Bull., 45, 710-714 (1997) https://doi.org/10.1248/cpb.45.710