Biopharmaceutical aspects of emulsions

Kakemi and co-workers have studied the mechanisms of intestinal absorption of drugs from O/W emulsions extensively using in vitro and in vivo models. In their first paper [220] on the topic they use as their starting point the equation of Bean and Heman-Ackah [221] derived for a preservative-emulsion system in which the concentration of active agent in the aqueous phase was related to the overall concentration in the system 

The authors argue that not only the concentration of drug but also the absolute amount has to be taken into account in considering the absorption process. The absorption of acetanilide from isopropyl palmitate emulsions (P = 1.05) decreased with increase in [D ]/[Dt] is almost unity over the whole range of 0 while decreased with increase of O. Comparison of percentage absorption 

It would be wrong to consider the oil phase as an inert carrier or even simply as a reservoir. Recent work has shown that the oil phase exerts some biological 

Modification of gastric residence times in determining absorption from oils and emulsions has also been implicated by Bates and Sequeira [226], a view recently confirmed by Palin et ai [227]. 

Oral administration to rats of DDT in solution in three oils of different chemical composition was found to yield significantly different plasma-concentration time curves (see Table 8.9). Emulsification of the oils with 6 % v/v Tween 80 had different effects on both the rate and extent of absorption and was dependent upon the nature of the oil. The effect of each oil on the total gut transit time of a co-administered Tc-sulphur colloid was investigated. The time taken for 50 % of the marker to be excreted was determined from faecal recoveries and whole body gamma scintigraphy. The sulphur colloid was most rapidly cleared in the presence of liquid paraffin (r5o . = 9.8 3.6h). There was no significant difference in the total transit times in the presence of Miglyol 812 ( 50% = 15.5 2.0h) and arachis oil (tso% = 14.1 1.1 h). Therefore, the differences in DDT absorption may only be explained in part by the effect of oils on total gut transit time. 

Traditionally, emulsions have been used to deliver oils (castor oil, liquid paraffin) in a palatable form. This is now a minor use, but there is a growing interest in the possibility of improving delivery by the use of lipid o/w emulsions as vehicles for lipophilic dmgs (e.g. diazepam, propofol) for intravenous use. Griseofulvin, presented as an emulsion, exhibits enhanced oral absorption an emulsion of indoxole has superior bioavailability over other oral forms. Medium-chain triglycerides and mono- and diglycerides promote the absorption of ceftriaxone and cefoxitin as well as ciclosporin. 

In the case of griseofulvin, administration in a fatty medium enhances absorption. Fat is emulsified by the bile salts, and the administration of an already emulsified form increases the opportunity for solubilisation and hence transport across the microvilli by fat absorption pathways. The influence of the emulsifier on membrane permeability is one factor that must be considered. Knowledge that particles may be absorbed from the gut by the gut-associated lymphoid tissue suggests that we may have to revise our views on the nature of absorption of many dmgs from the gastrointestinal tract. 

Dmg release from emulsions is related to the partition coefficient of the dmg and the volume of the disperse phase, as well as to the concentration of surfactant which might solubilise the dmg in the aqueous phase. 

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