Submicron emulsions

Zeevi, A., Klang, S., Alard, V., Brossard, F. and Benita, S. (1994) The design and characterization of a positively charged submicron emulsion containing a sunscreen agent. International Journal of Pharmaceutics, 108 (1), 57-58. 

Youenang Piemi, M.P., Korner, D., Benita, S. and Marty, J.P. (1999) Positively and negatively charged submicron emulsions for enhanced topical delivery of antifungal drugs. Journal of Controlled Release, 58, 177-187. 

Ilan, E., Amselem, S., Weisspapir, M., Schwarz, J., Yogev, A., Zawoznik, E., and Friedman, D., Improved oral delivery of desmopressin via a novel vehicle mucoadhesive submicron emulsion, P/jarm. Res., 13 1083-1087 (1996). 

Bunjes H., Siekmann B., and Westesen K., Emulsions of supercooled melts a novel drug delivery system, in Submicron Emulsions in Drug Targeting and Delivery, Benita S., ed., Harwood Academic Publishers, Amsterdam, 1998, 175. 

Sznitowska M. et al.. Bioavailability of diazepam from aqueous-organic solution, submicron emulsion and solid lipid nanoparticles after rectal administration in rabbits, Eur. J. Pharm. Biopharm., 52, 159, 2001. 

M.P. Krafft, J.G. Riess, J.G. Weers, in S. Benita (Ed.), Submicronic Emulsions in Drug Targeting and Delivery, Harwood Academic Publication, Amsterdam, 1998, pp. 235—333. 

Spontaneous emulsification of oils carrying drugs make SEDDS good candidates for the oral delivery of hydrophobic drugs with adequate oil solubility since the drug will be presented as a fine (submicron) emulsion that has a large surface area across which diffusion can take place rapidly, thereby facilitating absorption into the body. 

Schwarz J, Weisspapir M, Friedman D. Enhanced transdermal delivery of diazepam by submicron emulsion (SME) creams. Pharm Res 995 12 687-692. 

Sznitowska M, Janicki S, Dabrowska EA, Gajewska M. Physicochemical screening of antimicrobial agents as potential preservatives for submicron emulsions. Eur J Pharm Sci 2002(Jun) 15(5) 489-495. 

Typically, emulsions for parenteral use should have droplet size less tlpan ((generally 100-1000 nm), and hence are often called submicron emulsions, or (less properly) nanoemulsions. Use of the latter term is unfortunate and can lead to confusion, since their droplet size is actually larger than the microemulsion systems described earlier. The term nanoemulsion has been proposed to include metastable emuisfotSO nm as well as thermodynamically stable microemulsions (Sarker, 2005). Manufacture of submicron emulsions require special homogenization equipment, as will be described later. 

In addition to the concepts such as emulsions, submicron emulsions, and microemulsions introduced in Chapter 10 (Part I Parenteral Applications), the following concepts and background information are important for oral formulations. 

Baluom, M., D.I. Friedman, and A. Rubinstein. 1997. Absorption enhancement of calcitonin in the rat intestine by carbopol-containing submicron emulsions. Int J Pharm 154 235. 

Emulsions are two-phase systems formed from oil and water by the dispersion of one liquid (the internal phase) into the other (the external phase) and stabilized by at least one surfactant. Microemulsion, contrary to submicron emulsion (SME) or nanoemulsion, is a term used for a thermodynamically stable system characterized by a droplet size in the low nanorange (generally less than 30 nm). Microemulsions are also two-phase systems prepared from water, oil, and surfactant, but a cosurfactant is usually needed. These systems are prepared by a spontaneous process of self-emulsification with no input of external energy. Microemulsions are better described by the bicontinuous model consisting of a system in which water and oil are separated by an interfacial layer with significantly increased interface area. Consequently, more surfactant is needed for the preparation of microemulsion (around 10% compared with 0.1% for emulsions). Therefore, the nonionic-surfactants are preferred over the more toxic ionic surfactants. Cosurfactants in microemulsions are required to achieve very low interfacial tensions that allow self-emulsification and thermodynamic stability. Moreover, cosurfactants are essential for lowering the rigidity and the viscosity of the interfacial film and are responsible for the optical transparency of microemulsions [136]. 

Muchtar, S., et al. 1992. A submicron emulsion as ocular vehicle for delta-8-tetrahydrocannabinol Effect on intraocular pressure in rabbits. Ophthalmic Res 24 142. 

Naveh, N., et al. 2000. A submicron emulsion of HU-211, a synthetic cannabinoid, reduces intraocular pressure in rabbits. Graefes Arch Clin Exp Ophthalmol 238 334. 

Naveh, N., S. Muchtar, and S. Benita. 1994. Pilocarpine incorporated into a submicron emulsion vehicle causes an unexpectedly prolonged ocular hypotensive effect in rabbits. J Ocul Pharmacol 10 509. 

Zurowska-Pryczkowska, K., M. Sznitowska, and S. Janicki. 1999. Studies on the effect of pilocarpine incorporation into a submicron emulsion on the stability of the drug and the vehicle. Eur J Pharm Biopharm 47 255. 

Sznitowska, M., et al. 2001. In vivo evaluation of submicron emulsions with pilocarpine The effect of pH and chemical form of the drug. J Microencapsul 18 173. 

Sznitowska, M., et al. 2000. Increased partitioning of pilocarpine to the oily phase of submicron emulsion does not result in improved ocular bioavailability. Int J Pharm 202 161. 

Melamed, S., et al. 1994. Adaprolol maleate in submicron emulsion, a novel soft (3-blocking agent, is safe and effective in human studies. Invest Ophthalmol Vis Sci 35 1387. 

Garty, N., and M. Lusky. 1994. Pilocarpine in submicron emulsion formulation for treatment of ocular hypertension A phase II clinical trial. Invest Ophthalmol Vis Sci 35 2175. 

Klang, S.H., et al. 1999. Evaluation of a positively charged submicron emulsion of piroxicam on the rabbit corneum healing process following alkali burn. J Control Release 57 19. 

Tamilvanan, S., et al. 2001. Ocular delivery of cyclosporin A.I. Design and characterization of cyclosporin A-loaded positively charged submicron emulsion. STP Pharm Sci 11 421. 

Benita, S., and Levy, M. Y. Submicron emulsions as colloidal drug carriers for intravenous administration Comprehensive physicochemical characterization. J. Pharm. Sci. 82 1069-1079, 1993. 

Muchtar, S., Abdulrazik, M., Frucht-Pery, J., and Benita, S. (1997), Ex-vivo permeation study of indomethacin from a submicron emulsion through albino rabbit cornea, /. Controlled Release, 44(1), 55-64. 

Benita, S. (1998), Introduction and overview, in Benita, S., Ed., Submicron Emulsion in Drug Targeting Delivery, Harwood Academic,The Netherlands, pp.1-5. 

Benita, S. (1999), Prevention of topical and ocular oxidative stress by positively charged submicron emulsion, Biomed. Pharm., 53,193-206. 

Abdulrazik, M., Tamilvanan, S., Khoury, K., and Benita, S. (2001), Ocular delivery of cyclosporin A II. Effect of submicron emulsion s surface charge on ocular distribution of topical cyclosporin A, STP Pharma Sci, 11, 427-432. 

Yang, S. C., and Benita, S. (2000), Enhanced absorption and drag targeting by positively charged submicron emulsions, Drug Dev. Res., 50,476 186. 

Swietlikowska, D. W., and Sznitowska, M. (2006), Partitioning of parabens between phases of submicron emulsions stabilized with egg lecithin, Int. J. Pharm., 312, 174-178. 

Tamilvanan, S., Schmidt, S., Muller, R. H., and Benita, S. (2005), In vitro adsorption of plasma proteins onto the surface (charges) modihed-submicron emulsions for intravenous administration, Eur. J. Pharm. Biopharm., 59,1-7. 

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