Preparation and evaluation of w/o/w type emulsions containing vancomycin.

The objective of this contribution is to summarize the preparation and application of water-in-oil-in-water type multiple emulsions (w/o/w emulsions) entrapping vancomycin (VCM). Formulations of the emulsions (the composition of an oily phase or the type and concentrations of surfactants) and emulsification methods (a stirring method and a membrane method) or conditions (rotation rates, pore sizes of membrane or operation pressures) were evaluated in order to prepare stable w/o/w emulsions. The pharmaceutical properties of the w/o/w emulsions - particle sizes, viscosity, phase separation and drug entrapment efficiency were measured and evaluated. We prepared stable w/o/w emulsions with a particle size of about 3 micrometer and an entrapment efficiency of VCM of about 70%. When this emulsion was administered intravenously to rats, plasma concentrations of VCM were prolonged compared to the VCM solution alone. The results of this study show the potential of the w/o/w emulsions for several clinical applications as one of the drug delivery systems.

[1]  T. N. Jaiswal,et al.  Haemorrhagic septicaemia vaccines. , 1998, Vaccine.

[2]  A. Brodin,et al.  Prlonged drug release from multiple emulsions. , 1978, Acta pharmaceutica Suecica.

[3]  J. Adler-Moore,et al.  Pharmacology and toxicology of a liposomal formulation of amphotericin B (AmBisome) in rodents. , 1991, The Journal of antimicrobial chemotherapy.

[4]  M. Hashida,et al.  Studies on pharmaceutical modification of anticancer agents. II. Enhanced delivery of bleomycin into lymph by emulsions and drying emulsions. , 1975, Chemical & pharmaceutical bulletin.

[5]  Y. Kawashima,et al.  Drug Release from the Water-in-Oil-in-Water Multiple Emulsion in Vitro. II. Effects of the Addition of Hydrophilic Surfactants to the Internal Aqueous Compartment on the Release Rate of Secretin , 1993 .

[6]  M. Gallarate,et al.  On the stability of ascorbic acid in emulsified systems for topical and cosmetic use. , 1999, International journal of pharmaceutics.

[7]  B. Bivins,et al.  Clearance of 141C3-labeled microspheres from blood and distribution in specific organs following intravenous and intraarterial administration in beagle dogs. , 1980, Journal of pharmaceutical sciences.

[8]  T. N. Jaiswal,et al.  Protection, humoral and cell-mediated immune responses in calves immunized with multiple emulsion haemorrhagic septicaemia vaccine. , 1997, Vaccine.

[9]  Y. B. Lee,et al.  Prolonged release of tegafur from S/O/W multiple emulsion. , 1998, Drug development and industrial pharmacy.

[10]  M. Nakano,et al.  Comparative Study of Two Preparation Methods of w/o/w Emulsions : Stirring and Membrane Emulsification , 1997 .

[11]  M. Morishita,et al.  Enhanced colonic and rectal absorption of insulin using a multiple emulsion containing eicosapentaenoic acid and docosahexaenoic acid. , 1998, Journal of pharmaceutical sciences.

[12]  D. Nixon,et al.  CTL induction using synthetic peptides delivered in emulsions--critical role of the formulation procedure. , 1997, Vaccine.

[13]  T. Uchida,et al.  In vivo release of water-soluble drugs from stabilized water-in-oil-in-water (W/O/W) type multiple emulsions following intravenous administrations using rats. , 1993, Biological & pharmaceutical bulletin.

[14]  N. Li,et al.  The immobilization of urease using liquid-surfactant membranes. , 1972, Biochemical and biophysical research communications.

[15]  B. Mishra,et al.  Prolonged release of pentazocine from multiple O/W/O emulsions , 1989 .

[16]  S. Mataumoto,et al.  FORMATION AND APPLICATIONS OF MULTIPLE EMULSIONS , 1989 .

[17]  I. M. Walker,et al.  Measurement of the yield of multiple emulsion droplets by a fluorescent tracer technique , 1983 .

[18]  A. Florence,et al.  The formulation and stability of multiple emulsions , 1982 .

[19]  M. Nakano,et al.  Pharmacokinetics of Vancomycin after Intravenous Administration of a W/O/W Emulsion to Rats , 1997 .

[20]  K. Shinoda,et al.  Emulsions and Solubilization , 1986 .

[21]  J. Santoro,et al.  Vancomycin. A new old agent. , 1989, Infectious disease clinics of North America.

[22]  M. L. Shively Multiple emulsions for the delivery of proteins. , 1997, Pharmaceutical biotechnology.

[23]  W. Leader,et al.  Pharmacokinetic Optimisation of Vancomycin Therapy , 1995, Clinical pharmacokinetics.

[24]  L. A. Elson,et al.  Enhancement of the cancer chemotherapeutic effect of the cell cycle phase specific agents methotrexate and cytosine arabinoside when given as a water-oil-water emulsion. , 1974, European journal of cancer.

[25]  J. C. Price,et al.  Effect of non-ionic surfactant concentration and type on the formation and stability of W/O/W multiple emulsions: Microscopic and conductometric evaluations , 1991 .

[26]  Taizo Kimura,et al.  The pharmacokinetics of water-in-oil-in-water-type multiple emulsion of a new tacrolimus formulation , 1997, Lipids.

[27]  I. Bekersky,et al.  AmBisome (Liposomal Amphotericin B): A Comparative Review , 1998, Journal of clinical pharmacology.

[28]  Yoshiaki,et al.  Stabilization of Water/Oil/Water Multiple Emulsion with Hypertonic Inner Aqueous Phase. , 1992 .

[29]  M. Shimizu,et al.  Arterial‐injection chemotherapy for hepatocellular carcinoma using monodispersed poppy‐seed oil microdroplets containing fine aqueous vesicles of epirubicin. Initial medical application of a membrane‐emulsification technique , 1995, Cancer.

[30]  S. Matsumoto,et al.  Effect of sugars on the physicochemical properties of W/O/W emulsions , 1991 .

[31]  J. Grossiord,et al.  A topical W/O/W multiple emulsion containing several active substances : formulation, characterization and study of release , 1993 .

[32]  M. Kohda,et al.  The viscosity of W/O/W emulsions: An attempt to estimate the water permeation coefficient of the oil layer from the viscosity changes in diluted systems on aging under osmotic pressure gradients , 1980 .

[33]  N. Jain,et al.  A stable multiple emulsion system bearing isoniazid: preparation and characterization. , 1998, Drug development and industrial pharmacy.

[34]  M. Kohda,et al.  An attempt to estimate stability of the oil layer in W/O/W emulsions by means of viscometry , 1980 .

[35]  D. Pode,et al.  Doxil (Caelyx): an exploratory study with pharmacokinetics in patients with hormone-refractory prostate cancer , 2000, Anti-cancer drugs.

[36]  R. Geary,et al.  Vancomycin and insulin used as models for oral delivery of peptides , 1993 .

[37]  G. Gregoriadis,et al.  Tissue distribution of liposomes exhibiting long half-lives in the circulation after intravenous injection. , 1985, Biochimica et biophysica acta.

[38]  M. Newman,et al.  Pharmacokinetics, Biodistribution and Therapeutic Efficacy of Doxorubicin Encapsulated in Stealth® Liposomes (Doxil®) , 1994 .

[39]  W. Seifriz Studies in Emulsions. III-V , 1924 .

[40]  Y. Nishihara,et al.  O/W lipid emulsions for parenteral drug delivery. I. Pharmacokinetics of the oil particles and incorporated sudan II. , 1994, Biological & pharmaceutical bulletin.

[41]  Masanori Kohda,et al.  Water permeability of oil layers in W/O/W emulsions under osmotic pressure gradients , 1980 .

[42]  S. Fukushima,et al.  Preparation of and drug release from W/O/W type double emulsions containing anticancer agents. , 1983, Chemical & pharmaceutical bulletin.

[43]  T. Whateley,et al.  Absorption and lymphatic uptake of 5-fluorouracil in the rat following oral administration of w/o/w multiple emulsions , 1990 .

[44]  A. Khopade,et al.  Effects of drug concentration in inner aqueous phase and additives in oleaginous phase on release and bioavailability of isoniazid from multiple emulsion. , 1998, Drug development and industrial pharmacy.

[45]  A. Sette,et al.  Peptide vaccination using nonionic block copolymers induces protective anti-viral CTL responses. , 1999, Vaccine.

[46]  A. Florence,et al.  Some features of breakdown in water-in-oil-in-water multiple emulsions , 1981 .

[47]  B. Mishra,et al.  Multiple water-oil-water emulsions as prolonged release formulations of pentazocine , 1990 .

[48]  R. Hunter,et al.  Strong mucosal adjuvanticity of cholera toxin within lipid particles of a new multiple emulsion delivery system for oral immunization , 1997, European journal of immunology.

[49]  N. Jain,et al.  Lectin-functionalized multiple emulsions for improved cancer therapy. , 1998, Journal of drug targeting.

[50]  A. Florence,et al.  The Nature of the Oil Phase and the Release of Solutes from Multiple (w/o/w) Emulsions , 1986, The Journal of pharmacy and pharmacology.

[51]  S. Matsumoto W/O/W-type multiple emulsions with a view to possible food applications , 1986 .

[52]  M. Shimizu,et al.  Size of lipid microdroplets effects results of hepatic arterial chemotherapy with an anticancer agent in water-in-oil-in-water emulsion to hepatocellular carcinoma. , 1999, The Journal of pharmacology and experimental therapeutics.

[53]  M. Hashida,et al.  Dosage Form Characteristics of Microsphere-in-oil Emulsions. I : Stability and Drug Release , 1980 .

[54]  D. Burgess,et al.  Influence of Interfacial Rheological Properties of Mixed Emulsifier Films on the Stability of Water‐in‐Oil‐in‐Water Emulsions , 1998, The Journal of pharmacy and pharmacology.

[55]  孝也 田中,et al.  Methicillin resistant Staphylococcus aureus感染症に対するvancomycin持続投与の有用性と安全性 , 1994 .

[56]  I. M. Walker,et al.  [5] Multiple emulsions as targetable delivery systems , 1987 .

[57]  S. Matsumoto,et al.  PREPARATION OF W/O/W EMULSIONS IN AN EDIBLE FORM ON THE BASIS OF PHASE INVERSION TECHNIQUE , 1985 .

[58]  C. Elson In defense of mucosal surfaces. Regulation and manipulation of the mucosal immune system. , 1997, Advances in experimental medicine and biology.

[59]  S. Magdassi,et al.  A kinetic model for release of electrolytes from w/o/w multiple emulsions , 1986 .

[60]  B. K. Gupta,et al.  In vitro : in vivo correlation of indomethacin release from prolonged release W/O/W multiple emulsion system , 1993 .

[61]  K. Sugibayashi,et al.  Detoxication capacity of a multiple (w/o/w) emulsion for the treatment of drug overdose: drug extraction into the emulsion in the gastro-intestinal tract of rabbits. , 1979, Chemical & pharmaceutical bulletin.

[62]  D. Wasan,et al.  Formulation and Characterization of a Multiple Emulsion for Use as a Red Blood Cell Substitute , 1988 .

[63]  M. Shimizu,et al.  Particle control of emulsion by membrane emulsification and its applications. , 2000, Advanced drug delivery reviews.

[64]  J. Grossiord,et al.  Kinetics of swelling-breakdown of a W/O/W multiple emulsion: possible mechanisms for the lipophilic surfactant effect. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[65]  D. Whitehill,et al.  Stabilization of water/oil/water multiple emulsions by polymerization of the aqueous phases , 1982, The Journal of pharmacy and pharmacology.

[66]  S. Fukushima,et al.  Preparation of and drug release from W/O/W type double emulsions containing anticancer agents using an oily lymphographic agent as an oil phase. , 1987, Chemical & pharmaceutical bulletin.