Abstract
To develop the long acting nifedipine oral delivery with bioavailability enhancement, a nifedipine dry elixir (NDE) containing nifedipine ethanol solution in dextrin shell was prepared using a spray-dryer, and then coated nifedipine dry elixir (CNDE) was prepared by coating NDE with Eudragit acrylic resin. The physical characteristics and bioavailability of NDE and CNDE were evaluated, and then compared to those of nifedipine powder. NDE and CNDE, which were spherical in shape, had about 6.64 and 8.68–8.75 μm of geometric mean diameters, respectively. The amount of nifedipine dissolved from NDE for 60 min increased about 7- and 40-fold compared to nifedipine powder in pH 1.2 simulated gastric fluid and pH 6.8 simulated intestinal fluid, respectively. Nifedipine released from CNDE was retarded in both dissolution media compared with that from NDE. After oral administration of NDE, the Cmax and AUC0→8h of nifedipine in rat increased about 13- and 7-fold, respectively, and the Tmax of nifedipine was reduced significantly compared with those after oral administration of nifedipine powder alone. The AUC0→8h and Tmax of nifedipine in CNDE increased markedly and the Cmax of nifedipine in CNDE was significantly reduced compared to those in NDE. It is concluded that CNDE, which could lower the initial burst-out plasma concentration and maintain the plasma level of nifedipine over a longer period with bioavailability enhancement, might be one of potential alternatives to the marketed long acting oral delivery system for nifedipine.
Similar content being viewed by others
References
Ahn, H. J., Kim, K. M., and Kim, C. K., Enhancement of bioavailability of ketoprofen using dry elixir as a novel dosage form. Drug Dev. Ind. Pharm., 24, 697–701 (1998).
Amighi, K., Timmermans, J., Puigdevall, J., Baltes, E., and Moës, A. J., Peroral sustained-release film-coated pellets as a means to overcome physicochemical and biological drug-related problems. I. In vitro development and evaluation. Drug Dev. Ind. Pharm., 24, 509–515 (1998).
Hasegawa, A., Nakagawa, H., and Sugimoto, I., Bioavailability and stability of nifedipine-enteric coating agent solid dispersion. Chem. Pharm. Bull. (Tokyo), 33, 388–391 (1985a).
Hasegawa, A., Nakagawa, H., and Sugimoto, I., Application of solid dispersions of nifedipine with enteric coating agent to prepare a sustained-release dosage form. Chem. Pharm. Bull. (Tokyo), 33, 1615–1619 (1985b).
Hasegawa, A., Kawamura, R., Nakagawa, H., and Sugimoto, I., Physical properties of solid dispersions of poorly water-soluble drugs with enteric coating agents. Chem. Pharm. Bull. (Tokyo), 33, 3429–3435 (1985c).
Kerc, J., Srcic, S., Knez, Z., and Sencar-Bozic, P., Micronization of drugs using supercritical carbon dioxide. Int. J. Pharm., 182, 33–39 (1999).
Kim, C. K., Choi, J. Y., Yoon, Y. S., Gong, J. P., Choi, H. G., Kong, J. Y., and Lee, B. J., Preparation and evaluation of a dry elixir for the enhancement of the dissolution rate of poorly water-soluble drugs. Int. J. Pharm., 106, 25–32 (1994).
Kim, C. K. and Yoon, Y. S., Development of digoxin dry elixir as a novel dosage form using a spray-drying technique. J. Microencapsul., 12, 547–556 (1995).
Kim, C. K., Yoon, Y. S., and Kong, J. Y., Preparation and evaluation of flurbiprofen dry elixir as a novel dosage form using a spray-drying technique. Int. J. Pharm., 120, 21–31 (1995).
Lee, S. W., Kim, M. H., and Kim, C. K., Encapsulation of ethanol by spray drying technique: effects of sodium lauryl sulfate. Int. J. Pharm., 187, 193–198 (1999).
Menting, L. C. and Hoogstad, B., Volatiles retention during the drying of aqueous carbohydrate solutions. J. Food Sci., 32, 87–90 (1967).
Menting, L. C., Hoogstad, B., and Thijssen, H. A. G., Diffusion coefficients of water and organic volatiles in carbohydrate-water systems. Int. J. Food Sci. Technol., 5, 111–126 (1970).
Sato, J. and Kurusu, T., Process of manufacturing alcoholcontaining solid matter. U.S. Patent 3,786,159 (1974).
Sato, J., Kurusu, T., and Ota, M., Process for the preparation of alcohol-containing powders. U.K. Patent GB2110235A (1982).
Sugimoto, I., Kuchiki, A., Nakagawa, H., Tohgo, K., Kondo, S., Iwane, I., and Takahashi, K., Dissolution and absorption of nifedipine from nifedipine-polyvinylpyrrolidone coprecipitate. Drug Dev. Ind. Pharm., 6, 137–160 (1980).
Sugimoto, I., Sasaki, K., Kuchiki, A., Ishihara, T., and Nakagawa, H., Stability and bioavailability of nifedipine in fine granules. Chem. Pharm. Bull. (Tokyo), 30, 4479–4488 (1982).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Choi, JY., Jin, SE., Park, Y. et al. Development of coated nifedipine dry elixir as a long acting oral delivery with bioavailability enhancement. Arch. Pharm. Res. 34, 1711–1717 (2011). https://doi.org/10.1007/s12272-011-1015-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-011-1015-1