Solutol HS15, a nonionic surfactant, consisted of 70% of polyglycol mono- and di-esters of 12-hydroxystearic acid and 30% of free polyethylene glycol, could enhance the solubility of poor-water soluble drugs. Solutol HS15 has been reported to be a drug solubilizer, absorption, and permeation enhancer in solid dispersions, micelles, and liposomes. It can efficiently stabilize insoluble drugs by reducing the surface energy of the fine particles and preventing agglomeration and crystal growth.
Fig.1 The chemical structure of Solutol HS15.
The main penetration enhancing component, macrogol-15-hydroxystearate (e.g. Solutol HS15) is a composite material. Solutol HS15 has been found to enable the solubilisation of poorly soluble drugs and also inhibit to some degree the P-glycoprotein efflux mechanism. Hence for poorly soluble drugs, Solutol HS15 enables a higher degree of transport of drug into the systemic circulation and hence a higher bioavailability. Solutol HS15 was found by scientists to enhance the transport of hydrophilic drugs such as peptides and proteins (that are not poorly soluble nor a substrate for P-glycoprotein efflux) across the nasalmucosa in early studies in rats. When administering hGH nasally in rats with increasing concentrations of Solutol HS15, it was found that for a 10% w/v solution formulation a bioavailability of 49% was obtained in the first 2 h after administration. Furthermore, it was shown that the most effective ratio of Solutol HS15 to hGH was 4:1 on an mg to mg basis. Histopathology studies in rats after 5 days of repeated nasal administration showed that Solutol HS15 had no toxic effect on the nasal mucosa. It can be concluded that Solutol HS15 as a principle absorption enhancing component in this system, is a potent and non-toxic nasal absorption enhancer that warrants further development.
Fig.2 hGH serum levels in SD rats (0-6 h) after intranasal (I.N.) administration of hGH with Solutol HS15 at various concentrations, compared to subcutaneous injection (S.C.). (Illum, 2012)
Solubility of curcumin at physiological pH was significantly increased by forming solid dispersion (SD) with Solutol HS15. SD preparation transformed curcumin into an amorphous form and facilitated micellar incorporation, thereby preventing hydrolysis in an aqueous medium. In vitro drug release in pH6.8 buffer revealed that SD (1:10) improved the dissolution of curcumin with approximately 90% release of the drug within 1 h and was physically stable for an experimental period of 12 weeks. In vivo study in rats revealed that SD was effective in enhancing bioavailability significantly. Hence, the present formulation offers an effective means of overcoming problems related to the solubility, stability, and bioavailability of curcumin. Moreover, the present approach is simple and safe and can be designed as an oral dosage form filled into soft-gelatin or hard-gelatin capsules.
Fig.3 Dissolution profiles of curcumin, physical mixture, melting mixture and solid dispersion in pH6.8 buffer. (Seo, 2012)
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