`
`Innopharma EX1010, Page 1
`
`

`

`

`

`Vol. 50, No. 4, April1961
`
`ES 2%, and Stepanol ME 1 %) surfactants used
`in the concentrations mentioned in parenthesis
`were studied for the release of medicament using
`three in vitro methods, (a) radioactive isotope,
`(b) ba:cteriological, and
`(c) physicochemical
`methods.
`2. The, general pattern of the release of me(cid:173)
`dicament from all of the ointment bases remained
`the same when tested by these methods.
`3., The ointment prepared with two per cent
`anionic surfactant, Sipon ES, was found to be the
`most satisfactory hydrophilic ointment base.
`The increase in concentration of Sipon ES re(cid:173)
`tarded the release of medicament from ointment
`bases in all three in vitro methods.
`4. A modified physicochemical method is
`suggested to increase the sensitivity and the speed
`of the color zones produced per unit of time.
`5. A comparative discussion of three in vitro
`methods has been presented and it was concluded
`
`305
`
`that the radioactive isotope method was superior
`in both sensitivity and accuracy as well as the
`quantitative results which can be obtained per
`unit of time.
`
`i!
`I
`
`REFERENCES
`(1) Lockie, L. D., and Sprowls, J. B., THis JoURNAL, 38,
`222(1949).
`(2) Stark, J. F., Christian, J. E., and DeKay, H. G., ibid.,
`47, 223(1958).
`.
`(3) Barker, E. Y., Christian, J, E., and DeKay, H. G.,
`ibid., 45, 501(1956).
`.
`(4) Wand, R. A., and Ramsay, A., Can. Med. Assbc. J.,
`48, 121(1943).
`(5) Ruehle, C. L. A., and Brewer, C. M., U.S. Food and
`Drug Admin. Circular, No. 198.
`(6) Izgu, E. and Lee, C. 0., J. Am. Pharm. Assoc., Pract.
`Pharm. Ed., 15, 395(1954).
`-
`(7) Urkami, C., and Christian, J. E., Tms JouRNAL,
`42, 179(1953).
`(8) Gemel, D. I-I. 0 .. and Morrison, ]. C., J. Pharm. and
`Pharmacal., 9, 641(1957).
`(9) Patel, K. C., Banker, G. S., and DeKay, H. G., THIS
`}OURNAL, 50, 294(1951),
`(10) "Visking Dialysis Tttbing-Technical Infonnation,"
`Viskiug Co., 6733 West 65th St., Chicago 38, Ill.
`(11) Livingood, J, J., and Seaborg, G. T., Physiol. Revs.,
`54, 775(1938).
`(12) Bell, R. E., and Gram, R. L., ibid., 86, 212(1952).
`(13) Fox, C. L., Winfield, J. M., Slobody, L. B., Swindler,
`C. M., and Lattimer, J, K., J. Am. Med, Assoc., 148, 827
`(1952),
`
`Solubilization of Anti~inflammatory Steroids by
`Aqueous Solutions of Triton WR-1339
`
`By D. E. GUTTMANt, W. E. HAMLIN,]. W. SHELL, and]. G. WAGNER
`
`Cleat· solutions 'of anti-inflammatory steroids, which have concentrations of steroid
`considerably greater than the water solubilities of the stet·oids, are being sold
`commercially for ophthalmic use. The present study was undertaken to obtain
`quantitative data on the solubilizing power of Triton WR-1339 for th1'ee anti-in(cid:173)
`flammatm·y steroids. The appat·ent solubility of each of the steroids, prednisolone,
`methylpt·ednisolone, and fluorometholone, in an aqueous solution of Triton WR-
`13 3 9 was found to be lineady dependent on the per cent Triton present. Both the
`slopes of the linear solubility plots and the watet· solubilities of the steroids at·e, in
`the ordet·, p1'ednisolone > methylprednisolone > fluorometholone. The marked
`diffet·ence in the solubility of fluorometholone in aqueous solutions of Triton WR-
`13 39 from the othet· two steroids having a 21-hydt'oxyl group indicates that an en(cid:173)
`tirely diffet•ent pha1'maceutical problem is involved with the steroid having the type
`of side chain present in fluo1'ometholone.
`
`vARIOUS AUTHORS (1-14) have reported the
`use of surface-active materials, e. g., proteins,
`bile salts, and surfactants, to solubilize steroid
`hormones. For ophthalmic use it is desirable to
`prepare clear solutions of anti-inflammatory
`steroids which have concentrations of steroid
`considerably greater than their water solubility.
`The surface-active materials used in such prep(cid:173)
`arations must have sufficient solubilizing power to
`attain the necessary steroid concentration and
`must be nonirritating and noninjmious .to the eye.
`Johnson (13, 14) studied a large number ·of
`
`Received June 3, 1950, ftotn the Research Laboratories,
`The Upjohn Co., Kalamazoo, Mich.
`Accepted for publication August 4, 1960.
`'I" Present address: College of Pharmacy, The Ohio State
`University,. Columbus.
`
`surfactants and found that both Triton WR-1339
`and Tween 80 were satisfactory for preparing
`suitable aqueous solutions of the adrenalcortical
`honnones. 1
`The present study was undertaken to obtain
`quantitative data on the solubilizing power of
`Triton WR-1339 for
`three anti-inflammatory
`steroids: prednisolone, methylprednisolone, ancl
`flttotometholone.
`
`EXPERIMENTAL
`
`Materials.-The prednisolone was recrystallized
`once from alcohol-water, then dried for twelve hours
`
`t Two of the comtnercial products are Eye Drops Optef,
`0. 2% and Eye Dl"Ops Neo-Deltef, 0. 2%, sold by The Upjohn
`Co.
`
`Innopharma EX1010, Page 3
`
`

`

`

`

`