Colloidal anhydrous silica suppositories

Morphine sulphate in a matrix of a fatty base (Witepsol W25) with colloidal anhydrous silica (Aerosil R 972 ) and hydroxypropylmethylceUulose (HPMC 4000) [10] showed an absorption rate and a biological availability equivalent to orally given morphine sulphate retard tablets (MS Contin ). Such suppositories can be made as a regular pharmacy preparation [11] but in our opinion this requires more convincing evidence that morphine release is sufficiently reproducible. MS-Contm suppositories (not available in all countries) have a fatty base with sodium alginate and calcium phosphate [12]. 

Wetting of strongly hydrophobic active substances can be so difficult that the solid particles will not get dispersed properly and float on the water. Polysorbate 80 (0.1-0.15 %) can be added to the water to prevent this. Alternatively the solid active substance can be triturated with povidone or colloidal anhydrous silica, see Sect. 29.3. Addition of a surfactant such as polysorbate should be considered carefully, because unless in small amounts it may adversely affect the absorption comparable with the addition of surfactants to suppositories (see Sect. 11.3.2). 

Lubricants can counteract the formation of agglomerates of small particles and disperse pre-existing agglomerates. Colloidal anhydrous silica is added for this purpose in the preparation of suppositories (see Sect. 11.4.6) and in the preparation of oral suspensions (see Sect. 5.4.6). 

When silica is used, it should be considered that the release of aqueous soluble to very soluble active substances may be reduced. Silica increases the viscosity of the base which may impair the transport of the active substance to the interface between water and fat, thereby impairing active substance release. For water-soluble active substances, crossing the interface is rate determining (Sect. 16.2.4). For this reason the amount of silica has to be limited to 1 % of the weight of the active substance. A negative influence of anhydrous colloidal silica on active substance release is evident for amounts above 1.5-2 % of the suppository base [8i]. Concentrations above 1.5-2 % are used only for suppositories with an intentionally delayed release profile. 

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