Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
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Formulation Design and Evaluation of Ketorolac Tromethamine Hydrogel for Transdermal Delivery System

경피흡수를 위한 케토롤락 하이드로겔의 제제설계 및 평가

  • Cho, In-Sook (College of Pharmacy, Chungnam National University) ;
  • Lee, Gye-Won (Pharmaceutical Engineering, Konyang University) ;
  • Lee, Jong-Hwa (College of Pharmacy, Chungnam National University) ;
  • Jee, Ung-Kil (College of Pharmacy, Chungnam National University)
  • Published : 2003.03.20
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Abstract

Ketorolac tromethamine(KT) is a nonsteroidal agent with potent analgesic and moderate anti-inflammatory activity. The lipid-water partition coefficient of KT was evaluated and KT gel was formulated as a gel containing different pH, different concentrations of polymer (poloxamer 407, carbopol 941), propylene glycol, ethanol and various enhancers. The resulting KT gels were evaluated with respect to their viscosity, in vitro drug permeation rate through hairless mouse skin and stability. In n-octanol and chloroform, the lipid-water partition coefficient of KT was the highest at pH 4 phosphate buffer. The apparent viscosity of KT gel increased with an increase in gel pH, polymer and enhancer concentration. But the apparent viscosity of KT gel decreased with an increase in ethanol concentration. The permeation rate of KT through hairless mouse skin from gels different pH was maximum at pH 4 which is close to KT $pK_{a}$ 3.54. The permeation rate decreased with an increase in polymer, propylene glycol concentration. But the permeation rate increased with an increase in ethanol. The increase of drug concentration from 1 to 3% induced linear increase in permeation rate. The best enhancer was the combination of $Labrasol^{\circledR},\;Transcutol^{\circledR}$, oleic acid and l-menthol. In the accelerated stability test(25, 40 and $50{\circ}C$), pH 5 gel was most stable and pH 4 gel was most unstable for 90 days.

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References

  1. M.M.T. Buckley and R.N. Brogden, K-etorolac: A review ofits pharmacokinetic properties and therapeutic potential, Drugs, 39(1), 86-109 (1990) https://doi.org/10.2165/00003495-199039010-00008
  2. J.R. Gross, The evolution of absorbent materials : In Absorbent Polymer technology, L. Brannon-Peppas and R.S.Harland(Ed.), Elsevier, New York, U.S.A., PP. 3-22 (1990)
  3. A.S. Hoffman, Hydrogels-A Broad Class of Biomatehals : In Polymers in Medicine and Surgery, R.L. Kronenthal, Z.Oser and E. Martin(Ed.), Plenum Press, New York, U.S.A.,pp. 34-44 (1975)
  4. M.M. Welz and C.M. Ofner III, Examination of self-crosslinked gelatin as a hydrogel for controlled release, J.Pharm. Sci., 81(1), 85-90 (1992) https://doi.org/10.1002/jps.2600810117
  5. C.K. Shim and S.H Yeo, Albumin-crosslinked PVP hydrogel as a gastric retention platform, J. Kor. Pharm. Sci.,23(3), 145-153 (1993)
  6. H.L. Lueen, J.C. verhoef, G. Borchard, C.M. Lehr, A.G. de Boer and H.E. Junginger, Mucoadhesive polymers in peroral peptide drug delivery. II. Carbomer and polycarbophil arepotent inhibitors of the intestinal proteolytic enzyme trypsin, Pharm. Res., 12(9), 1293-1298 (1995) https://doi.org/10.1023/A:1016213405081
  7. M. Singh, R. Rathi, A. Singh, J. Heller, G.P. Talwar and J.Kopecek, Controlled release of LHRH-DT from bioerodible hydrogel microspheres, Int. J. Pharm., 76, R5-R8 (1991) https://doi.org/10.1016/0378-5173(91)90283-T
  8. R.M. Nalbandian, R.L. Henny and H.S. Wilks, Artificialskin II. Pluronic F-127 silver nitrate or silver lactate gel inthe treatment of thermal burns, J. Biomed. Mater. Res., 6, 583-590 (1972) https://doi.org/10.1002/jbm.820060610
  9. S. Miyazaki, Y. Ohkawa, M. Takeda and D. Attwood,Antitumor effect of Pluronic F-127 gel containing mitomycin C on sarcoma-180 ascites tumor in mice, Chem Pharm. Bull., 40(8), 2224-2265 (1992) https://doi.org/10.1248/cpb.40.2224
  10. S.H. Kam, E.S. Park and S.C. Chi, Skin permeation of indomethacin from gels, J. Kor. Pharm. Sci., 25(2), 129-136 (1995)
  11. C.M. Lehr, J.A. Bouwstra, W. Kok, A.G. de Boer, J.J. Tukker,J.C. Verhoef, D.D. Breimer and H.E. Jungmger, Effects of mucoadhesive polymer polycarbophil on the intestinal absorption of a peptide drug in the rat, J. Pharm. Pharmacol,4, 402-407 (1992)
  12. M.D. Vlachou, D.M. Rekkas, P.P. Dallas and N.H. Choulis,Development of and in vitro evaluation of gnseofulvin gelsusing Franz diffusion cells, Int. J. Pharm., 82, 47-52 (1992) https://doi.org/10.1016/0378-5173(92)90070-I
  13. K. Kakemi, T. Ahta, R. Hori and R. Konish, Absorption andexcretion of drugs XXX. Absorption of barbituric acid derivatives from rat stomach, Chem. Pharm. Bull., 15(10),1534-1539 (1967) https://doi.org/10.1248/cpb.15.1534
  14. P.C. Chen-Chow and S.G. Frank, In vitro release of lidocainefrom Pluronic F-127 gels, Int. J. Pharm., 8, 89-99 (1981) https://doi.org/10.1016/0378-5173(81)90013-2
  15. F. Kaiho, Y. Takahashi, R. Ichihara, A. Watanabe, T. Yamashitaand Y. Kato, Application of fatty alcohol to pharmaceuticaldosage form. III. Percutaneous absorption of indomethacin from fatty alcohol and propylene glycol (FAPG) bases consisting of a mixture of fatty alcohol and propylene glycol,Yakugaku Zasshi, 106(1), 47-53 (1986) https://doi.org/10.1248/yakushi1947.106.1_47