Oral solubilisates

Formulations of the kind described above have been used quite widely in solubilising lipophilic drugs and vitamins, for oral, parenteral, and transdermal drug delivery. We consider the 2 design plus centre point tested in an animal model for the pharmacokinetic profile or pharmacological effect of the solubilised active substance. If each of the formulation was tested in two animals, with no testing of different formations on the same animal, the analysis would be identical to that of the solubility experiment above. The major part of the variance consists of that between animals and within the same animal o/, where cF = + a/. It is... 

Another, though less well-characterised, determinant of oral drug absorption is biliary function, which affects the ability to solubilise and absorb lipophilic drugs. Immature transportation and secretion of biliary salts in the neonatal period may affect drug absorption. 

Ten healthy subjects were given a single 10-mg/kg oral dose of ciclosporin with and without a 0.1-mL/kg oral dose of vitamin E (d-alpha tocopheryl polyethylene glucose 1000 succinate Liqui-E). The AUC of the ciclosporin increased by 60%, and it was suggested that absorption was increased due to improved solubilisation and micelle formation within the gut, or that decreased intestinal metabolism occurred. In contrast, another study in 12 healthy subjects found that vitamin E 800 units daily for 6 weeks reduced the AUC of a single 5-mg/kg dose of ciclosporin by 21%.2... 

The properties of the active substance dominate and often restrict the choice of the type of oral liquid. Oral liquids are classified according to their physical properties as solutions, suspensions, emulsions and solubilisates. Solutions and suspensions are treated in depth because they are most often dealt with in daily practice. 

Solutions Suspensions Emulsions Solubilisates Oral liquids Syrup Flavour Acceptable daily intake Colour Taste Feeding mbe Preparation Formulation... 

Biopharmaceutical aspects are shortly dealt with, followed by formulation and preparation method of oral solutions, suspensions, emulsions and solubilisates. 

Solubilisates for oral use colloidal solutions of a liquid active substance in an inuniscible liquid this term is not on the list of EDQM standard terms. 

Different oral liquid dosage forms offer the possibility to adjust the dosage form optimally to the requirements. The options are solutions, suspensions, emulsions or solubilisates. The flow scheme in Fig. 5.1 shows a route to the oral liquid form that is to be preferred due to the qualities of the active substance, particularly solubility, stability and taste. The required concentration influences the choice as well. 

The main choice will be between an oral solution and an oral suspension. For some active substances an emulsion or solubilisate is the appropriate form. However in some cases (e.g. because of an intermediate solubility of the active substance) the pharmacist will have no other option than to dispense an oral solid dosage form and instruct the patient how to manipulate it safely (see Sect. 37.6.2). Proper consideration of the options may prevent formulation mistakes with probably severe consequences. This especially applies to the unreflected use of suspending bases for rendering an oral solid into an oral liquid. 

Water supports the growth of micro-organisms, therefore oral aqueous solutions, suspensions, emulsions and solubilisates in multidose containers should be preserved. Preservatives may be used for that purpose as well as excipients with preservative properties, such as propylene glycol. See Sect. 23.8 for extensive information on preservatives. Table 5.18 summarises preservatives with properties especially relevant for oral liquids. 

Many poorly water soluble substances can, molecularly disperse, adsorb or absorb on or into micelles. These micellar solutions are optically clear. This is called solubilisation. Examples from the Dutch formulary FNA are oral aqueous preparations with vitamin A (retinol palmitate) or D (chole-calciferol (Table 18.15)). Another example is a licensed oral mixture with ciclosporin. 

Syrups are a very commonly used form of sugars. They contain approximately 45-65 % of sugar, water and a preservative. Sometimes a flavouring is added. The preservative is most often methyl parahydroxybenzoate 0.1-0.15 %. Syrups can be very useful for improving the taste of oral liquid preparations and sometimes they can be used to stabilise a solubilisate of oil and polysorbate, e.g. in a vitamin A micellar solution (Table 23.12). 

In pharmacy preparations several different types of disperse systems are found. Liquid dispersions are dispersions in which a solid substance is dispersed into a liquid substance, such as suspensions for cutaneous applications and oral suspensions, and dispersimis in which a liquid is dispersed in a non-miscible liquid, such as emulsions and solubilisations. 

The dispersion of a liquid into another liquid with which it is immiscible to obtain a sufficiently physically stable product is only possible by emulsifying or solubilising, using surface-active substances (tensides, surfactants). This process is applied in the preparation of creams and solubilisations. In oral emulsions surface-active substances are not used, but instead viscosity enhancers that possess little surface activity. Below the preparation of emulsirMis and solubilisations is briefly discussed. 

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