Multiple emulsions drug release from

Mechanisms of drug release from multiple emulsion systems include diffusion of the dmg molecules from the internal droplets (1), from the medium of the external droplets (2), or by mass transfer due to the coalescence of the internal droplets (3), as shown in Fig. 7.16(b) 

Figure 22 Drug-release profile of isoniazid from multiple emulsion based on imi/oligo/droplet internal phase. (From Ref 57.)

Brodin AF. 1978. Drug release from oil-water-oil (O/W/O) multiple emulsion systems. Acta Pharm Suec 15 111-113. 

The release of electrolytes and drugs from multiple emulsions can, in principle, proceed via two possible mechanisms  

For drug delivery applications, it is clear that the release from W/O/W multiple emulsion occurs either by transport through the oily membrane or by its breakdown. In the first case, and depending on the affinity of the molecule for the oily phase, the transport is due to molecular diffusion (Fick diffusion) or to diffusion facilitated by certain surfactants that take on the role of carriers. Transport through the oily membrane will not be considered here. This chapter is devoted to an examination of the breakup mechanisms, as are produced by swelling or under shear. 

Figure 19 Drug release studies from various Rifampicin formulations W/O/W multiple emulsions uneoated (X), coated ( ), uncoated formulation with serum (V), coated formulation with serum (+), plain drug (O). drug with albumin (A) (125).

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

Omotosho JA, Florence AT, Whateley TL. 1989. Release of 5-fluorouracil from intramuscular W/OAV multiple emulsions. Biopharm Drug Dispos 10 257-268. 

Omotosho, J.A. Whateley, T.L. Florence, A.T. Release of 5-fluorouracil from intramuscular w/o/w multiple emulsions. Biopharm. and Drug Disposit 1989,10, 257-268. 

A kinetic model, adapted from that of Higuchi for release of dispersed drugs from polymeric matrices, was found to be suitable for the release of electrolytes from multiple emulsions. The existence of a diffusion-controlled mechanism was experimentally confirmed. This mechanism is facilitated as the concentration of reverse micelles formed in the oil phase increases.  

Miyakawa T, Zhang W, Uchida T, Kim NS, Goto S. 1993. In vivo release of water-soluble drugs from stabilized water-in-oil-in-water (W/OAV) type multiple emulsions following intravenous administrations using rats. Biol Pharm Bull 16(3) 268-272. 

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). 

We have shown that the NMR self-diffusion method is sensitive to the mean displacement of a molecule of interest on the time scale of the NMR experiment (A). This fact allows us to measure molecular transport inside the emulsion droplets, as in the case of determination of droplet sizes, and the exchange between the emulsion droplets, as in the case of highly concentrated emulsions. In more complex systems the NMR self-diffusion method is sensitive to the molecular exchange between the emulsion droplets and the continuous phase, as in the case of multiple emulsions. Many emulsion systems are currently used as carriers for drugs or other bioactive substances, such as pesticides. The selective measurement of the diffusivity of the individual components within flic emulsion system is therefore of theoretical and practical relevance. The NMR self-diffusion technique is an appropriate tool to study the drug release from emulsion droplets. This useful information may be obtained in a rapid and nondestructive way. 

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