Examples of Solid Dispersion

Solid dispersion is mainly used to improve dissolvability in water of a poorly water-soluble drug in a pharmaceutical composition (disclosed in U.S. Patents 6,753,330, 6,899,899, 6,677,362), to mask the taste of the drug substance (disclosed in U.S. Patents 7,115,280 and 7,112,336), and to prepare rapid disintegration oral tablets (disclosed in U.S. Patent 6,899,899). However, solid dispersions are used to produce sustained-release microspheres using tedious methods such as water-in-oil emulsions (disclosed in U.S. Patent 5,556,642).  Three methods are commonly used for such preparation, and they are solvent-based method, fusion-melt method and fusion-solvent method. And here, we review how this technology applied to the drug products:

1. Modigraf® (Tacrolimus): This immunosuppressant medication uses spray drying technology to disperse tacrolimus in a solid matrix, significantly improving its oral bioavailability compared to the crystalline form. (1)

2. Zortress® (Everolimus): Similar to Modigraf®, Zortress® utilizes spray drying to enhance the oral absorption of everolimus, another immunosuppressant drug. This improves its effectiveness in treating certain cancers and preventing transplant rejection. (1)

3. Norvir® (Ritonavir): This HIV protease inhibitor probably employs melt extrusion technology to disperse ritonavir, leading to higher and faster blood levels compared to the traditional tablet form. This allows for reduced dosing frequency and improved viral suppression. (2)

4. Onmel® (Itraconazole): This antifungal medication leverages melt extrusion to transform poorly soluble itraconazole into a highly bioavailable solid dispersion. This translates to shorter treatment durations and potentially fewer side effects. (3)

Reference

1. John M. Baumann, et al, Engineering Adv. in Spray Drying for Pharmaceuticals, Annual Reviews

2. Hengqian Wu et al, Effect of different seed crystals on the supernaturation state of ritonavir tablets prepared by hot-melt extrusion, Eur. J. of Pharm. Sci. 185(2023) 106440.

3, Venkata Raman Kallakunta et al, An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part I Expert Opin Drug Deliv. 2019 May ; 16(5): 539–550.