Prolonged release, from multiple emulsions

Brodin AF, Kavaliunas DR, Frank SG. 1978. Prolonged drug release from multiple emulsions. Acta Pharm Suec 15 1-10. 

Nakhare S, Vyas SP. Prolonged release of rifampicin from internal phase of multiple w/o/w emulsion systems. Indian ] Pharm Sci 1995 57 71-77. 

Multiple emulsions usually refer to series of complex two-phase systems that result from dispersing an emul sion into its dispersed phase. Such systems are often referred to as water-in-oil-in-water (W/OAV) or oil-in-water-in-oil (O/W/0) emulsions, depending on the type of internal, intermediate, and continuous phase. Multiple emulsions were early recognized as promising systems for many industrial applications, such as in the process of immobilization of proteins in the inner aqu eous phase (37) and as liquid membrane systems in extraction processes (38). W/O/W emulsions have been discussed in a number of technical applications, e.g., as prolonged drug-delivery systems (39-44), in the context of controlled-release formulations (45), and in pharmaceutical, cosmetic, and food (46) applications. 

Ketamine leaves the blood very rapidly to be distributed into the tissues. The recommended dosage of intravenous Ketamine is 2.5—20 mg/kg. The objective of the study was to test the concept that a multiple emulsion could be formulated which has high porosity and lower viscosity at 37°C consistent with its intended use for sustained drug release and to prolong the half-life of the anesthesia. The results showed that 8.2% of the Ketamine was released (100 mg/ml in the inner phase) after 10 min, 67.0% at 30 min, and 95.5% at 60 min from the Ketamine/OAV multiple emulsion in a well-controlled manner (Figs. 23 and 24). 

Yoshioka T, Ikeuchi K, Hashida M, Muranishi S, Sezaki H. 1982. Prolonged release of bleomycin from parenteral gelatin sphere-in-oil-in-water multiple emulsion. Chem... 

The absence of monomeric surfactant in the intermediate aqueous phase of the multiple emulsion prevented uncontrolled release of the drug through micellar diffusion controlled transport. Flumethrin release rates from the inner oil phase (Oi) imply that an interfacial barrier prolonged the release of the entrapped drug at a rate governed by its ability to partition into and to diffuse through the interfadal inner polymeric film as well as through the intermediate aqueous phase. 

The use of pharmaceuticals in form of emulsions is of special interest. Thus, for example, o/w emulsions stabilised by surfactants, such as mono- and diglycerides, are successfully used as pseuo-doxime-proxetil protection from intestinal lumen hydrolysis through oral administration [128]. Multiple w/o/w emulsions stabilised by Tween 20/Span 20 or Tween 80/Span 80 mixtures contributed to a prolonged retention of cytarabine in one of the phases, and its gradual release ensured a prolonged action of the drug [129]. 

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