Abstract
Sink conditions are often violated when using conventional release methods for dispersed systems. A novel reverse dialysis bag method was designed to overcome this problem. Model drug transport rates from submicron emulsions obtained using the conventional diffusion cell method and this novel method were compared. In the side-by-side diffusion cell method, emulsions were placed in the donor chamber and surfactant/buffer solutions in the receiver chamber. In the novel dialysis bag method, emulsions were diluted infinitely in the donor phase and surfactant/buffer solutions were placed in the receiver phase (dialysis bags). Slow release rates and linear release profiles were obtained using the side-by-side diffusion cell method apparently due to limited model drug solubility in the donor chamber resulting in violation of sink conditions. Biphasic release profiles were obtained using the dialysis bag method apparently due to an initial rapid release of free and micellar solubilized model drug from the donor to the receiver chambers followed by slow release from the oil droplets. Using both release methods, an initial increase and latter decrease in release rates were observed with increase in surfactant concentration. The initial increase was considered to be due to a decrease in the model drug oil-in-water partition coefficients and the subsequent decrease in release rates was due to micellar shape change (spheres to rods) causing a decrease in diffusion rates. Sink conditions were violated using the side-by-side diffusion cell method but were maintained in the dialysis bag method since emulsions were diluted infinitely in the donor phase.
Similar content being viewed by others
References
Hansrani PK, Davis SS, Groves MJ. The preparation and properties of sterile intravenous emulsions. J Parenter Sci Technol. 1983;37:145–150.
Davis SS, Hadgraft J, Palin KJ. Medical and pharmaceutical applications of emulsions. In. Becher P, ed. Encyclopedia of Emulsion Technology. New York: Dekker; 1985:159–238.
Davis SS, Washington C, West P, Illum L, Liversidge G, Sternson L. Kirsh R. Lipid emulsions as drug delivery systems. Ann N Y Acad Sci. 1987;507:75–88.
Singh M, Ravin JL. Parenteral emulsions as drug carrier systems. J Parenter Sci Technol. 1986;40:34–41.
Boyett JB, Davis CW. Injectable emulsions and suspensions. In: Liberman HA, Rieger MM, Banker GS eds. Pharmaceutical Dosage Forms: Disperse Systems. New York: Dekker; 1989:379–416.
Prankerd RJ, Stella VJ. The use of oil-in-water emulsions as a vehicle for parenteral drug administration. J Parenter Sci Technol. 1990;44:139–149.
Collins-Gold LC, Lyons RT, Bartholow LC. Parenteral emulsions for drug delivery. Adv Drug Deliv Rev. 1990;5:189–208.
Washington C. Evaluation of non-sink dialysis methods for the measurement of drug release from colloids: effects of drug partition. Int J Pharm. 1989;56:71–74.
Hashida M, Liao MH, Muranishi S, Sezaki H. Dosage form characteristics of microsphere-in-oil emulsion II. Examination of some factors affecting lymphotropicity. Chem Pharm Bull. 1980;28:1659–1666.
Miyazaki S, Hashiguchi N, Hou WM, Yokouchi C, Takada M. Preparation and evaluation in vitro and in vivo fibrinogen microspheres containing adriamycin. Chem Pharm Bull. 1986;34:3384–3393.
Armoury N, Fessi H, Devissauget JP, Puisieux F, Benita S. In vitro release kinetic pattern of indomethacin from poly (d,1-lactic) nanocapsules. J Pharm Sci. 1990;79:763–767.
Friedman D, Benita S. A mathematical model for drug release from o/w emulsions: Application to controlled release morphine emulsions. Drug Dev Ind Pharm. 1987;13:2067–2086.
Lostritto RT, Goei L, Silvestri SL. Theoretical considerations of drug release from submicron oil-in-water emulsions. J Parenter Sci Technol. 1987;41:215–219.
Sasaki H, Takakura Y, Hashida M, Kiamura T, Sezaki H. Antitumor activity of lipophilic prodrugs of mitomycin C entrapped in liposome or o/w emulsion. J Pharm Dyn. 1984;7:120–130.
Gupta PK, Hung CT, Perrier DG Quantiation of the release of doxorubicin from colloidal dosage forms using dynamic dialysis. J Pharm Sci. 1987;76:141–145.
Armoury N, Fessi H, Devissauget JP, Puisieux F, Benita S. Physicochemical characterization of polymeric nanocapsules and in vitro release evaluation of indomethacin as a drug model. Sci Technol Pract Pharm. 1989;5:647–651.
Desai MP, Labhasetwar V, Walter E, Levy RJ, Amidon GL. The mechanism of uptake of biodegradable microspheres in caco-2 cells is size dependant. Pharm Res. 1997;14:1568–1573.
Burgess DJ, Davis SS, Tomlinson E. Potential use of albumin microspheres as a drug delviery systems. I. Preparation and in vitro release of steroids. Int J Pharm. 1987;39:129–136.
Koosha F, Muller RH, Davis SS. A continuous flow system for in vitro evaluation of drug-loaded biodegradable colloidal barriers. J Pharm Pharmacol. 1988;40:131P.
Yoon KA, Burgess DJ. Mathematical modelling of drug transport in emulsion systems. J Pharm Pharmacol. 1988;50:601–610.
Silvestri S, Lostrito RT. Theoretical evaluation of dispersed droplet radii in submicron oil-in-water emulsions. Int J Pharm. 1989;50:141–146.
Author information
Authors and Affiliations
Corresponding author
Additional information
Published: August 31, 1999.
Rights and permissions
About this article
Cite this article
Chidambaram, N., Burgess, D.J. A novel in vitro release method for submicron-sized dispersed systems. AAPS PharmSci 1, 11 (1999). https://doi.org/10.1208/ps010311
Received:
Accepted:
Published:
DOI: https://doi.org/10.1208/ps010311