Improving Tenoxicam Solubility and Bioavailability by Cosolvent System
The formulation study of tenoxicam, a poorly water-soluble drug, was developed by use of a ternary cosolvent system and has significantly enhanced the solubility. Additionally, the relative bioavailability of testing formulation was also evaluated by New Zealand rabbit with a single i.m. injection. The three-phase diagram for dimethylsulfoxide (DMSO)/propylene glycol/water, DMSO/ethanol/water, and DMSO/polyethoxylated castor oil/ethanol system was developed. The volume ratio of 5:4:1 in the DMSO/polyethoxylated castor oil/ethanol system resulted in a more suitable vehicle than other systems, with a high solubility (20.73 mg/ml) and low viscosity (10.0 Cp). A pharmacokinetic study of bioequivalence (F rel = 0.89) was also obtained. The present study not only provides a novel strategy improving tenoxicam solubility but also helps further scientific knowledge for the development of parenteral formulations.
- C. Kim, Y. Y. Hwang, J. Y. Chang, H. G. Choi, S. J. Lim, and M. K. Lee. Development of a novel dosage form for intramuscular injection of titrated extract of Centella asiatica in a mixed micellar system. Int. J. Pharm. 220:141–147 (2001). CrossRef
- A. Yoshida, M. Yamamoto, T. Irie, F. Hirayama, and K. Uekama. Some pharmaceutical properties of 3-hydroxypropyl- and 2,3-dihydroxypropyl-beta-cyclodextrins and their solubilizing and stabilizing abilities. Chem. Pharm. Bull. (Tokyo). 37:1059–1063 (1989).
- P. Tilleul, B. Mons, C. Schmitt, J. M. Laporte, and D. Begue. Intravenous drug preparation practices: a survey in a French university hospital. Pharm. World Sci. 25:276–279 (2003). CrossRef
- J. S. Trivedi, and M. L. Wells. Solubilization using cosolvent approach. Liu IR, (eds.), Water-Insoluble Drug Formulation, Interpharm, Denver, Colorado, 2000, pp. 141–168.
- R. G. Strickley. Solubilizing excipients in oral and injectable formulations. Pharm. Res. 21:201–230 (2004). CrossRef
- N. Seedher, and S. Bhatia. Solubility enhancement of Cox-2 inhibitors using various solvent systems. AAPS PharmSciTech. 4:E33 (2003). CrossRef
- H. W. Hsu, Y. J. Cheng, L. K. Chen, Y. P. Wang, C. J. Lin, C. N. Lee, and W. Z. Sun. Differential analgesic effect of tenoxicam on the wound pain and uterine cramping pain after cesarean section. Clin. J. Pain. 19:55–58 (2003). CrossRef
- J. L. Mason, and G. J. Hobbs. Simple method for the analysis of tenoxicam in human plasma using high-performance liquid chromatography. J. Chromatogr. B Biomed. Appl. 65:410–415 (1995). CrossRef
- W. J. Loos, J. Szebeni, A. J. ten Tije, J. Verweij, D. M. van Zomeren, K. N. Chung, K. Nooter, G. Stoter, and A. Sparreboom. Preclinical evaluation of alternative pharmaceutical delivery vehicles for paclitaxel. Anticancer Drugs. 3:767–775 (2002). CrossRef
- H. Liu, C. Sabus, G. T. Carter, C. Du, A. Avdeef, and M. Tischler. In vitro permeability of poorly aqueous soluble compounds using different solubilizers in the PAMPA assay with liquid chromatography/mass spectrometry detection. Pharm. Res. 20:1820–1826 (2003). CrossRef
- B. K. Kang, J. S. Lee, S. K. Chon, S. Y. Jeong, S. H. Yuk, G. Khang, H. B. Lee, and S. H. Cho. Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs. Int. J. Pharm. 274:65–73 (2004). CrossRef
- D. K. Lee, and D. P. Wang. Formulation development of allopurinol suppositories and injectables. Drug Dev. Ind. Pharm. 25:1205–1208 (1999). CrossRef
- C. Udata, J. Patel, D. Pal, E. Hejchman, M. Cushman, and A. K. Mitra. Enhanced transport of a novel anti-HIV agent–cosalane and its congeners across human intestinal epithelial (Caco-2) cell monolayers. Int. J. Pharm. 250:157–168 (2003). CrossRef
- K. Kawakami, K. Miyoshi, and Y. Ida. Solubilization behavior of poorly soluble drugs with combined use of Gelucire 44/14 and cosolvent. J. Pharm. Sci. 93:1471–1479 (2004). CrossRef
- T. Stebler, and T. W. Guentert. Bioavailability of intramuscularly administered tenoxicam. Biopharm. Drug Dispos. 14:483–490 (1993). CrossRef
- D. Chen, D. Song, M. G. Wientjes, and J. L. Au. Effect of dimethyl sulfoxide on bladder tissue penetration of intravesical paclitaxel. Clin. Cancer Res. 9:363–369 (2003).
- G. Ehninger, U. Schuler, U. Renner, M. Ehrsam, K. P. Zeller, J. Blanz, R. Storb, and H. Deeg. Use of a water-soluble busulfan formulation–pharmacokinetic studies in a canine model. Blood. 85:3247–3249 (1995).
- M. Hassan, Z. Hassan, C. Nilsson, M. A. Rehim, S. Kumlien, B. Elfsson, and N. Kallberg. Pharmacokinetics and distribution of liposomal busulfan in the rat: a new formulation for intravenous administration. Cancer. Chemother. Pharmacol. 42:471–478 (1998). CrossRef
- U. S. Schuler, M. Ehrsam, A. Schneider, H. Schmidt, J. Deeg, and G. Ehninger. Pharmacokinetics of intravenous busulfan and evaluation of the bioavailability of the oral formulation in conditioning for haematopoietic stem cell transplantation. Bone Marrow Transplant. 22:241–244 (1998). CrossRef
- Improving Tenoxicam Solubility and Bioavailability by Cosolvent System
Volume 10, Issue 1 , pp 166-171
- Cover Date
- Online ISSN
- Springer US
- Additional Links
- cosolvent system
- poorly water-soluble drug
- Industry Sectors
- Author Affiliations
- 1. Department of Pharmacy Practice, Tri-Service General Hospital, Neihu, Taipei, Taiwan
- 2. School of Pharmacy, National Defense Medical Center, Neihu, Taipei, Taiwan
- 3. Institute of Preventive Medicine, National Defense Medical Center, Sansia, 90048-700, Taipei, Taiwan, Republic of China