A solid dispersion is a dispersion of one or more compound(s) in an inert carrier at solid state. The dispersed compounds can be in individual molecule unities or in clusters, such as in particles. Solid dispersion is commonly prepared by three different methods and they are solvent-based, fusion-melt and hybrid fusion-solvent methods.
[1] Solvent-based Method
The solvent-based method commonly uses a co-solvent to intimately disperse or dissolve the drug and carrier molecules together, and then evaporates the solvent by evaporation. Then, the researchers collect the solid dispersion as a powdered mass. This process is lengthy and expensive.
[2] Fusion-melt Method
The fusion-melt involves melting the compound(s) and the carrier components together at temperatures at or above the melting point of all components. In the fusion process, researchers blend the compound and carrier in a suitable mixer. They heat, melt the blend and then cool the molten mixture rapidly to provide a congealed mass. They mill this mass to produce powders at desired particle size ranges.
[3] Fusion-solvent Method
Researchers often use hybrid fusion-solvent method if thermal instability and immiscibility between the compound(s) and the carrier are present. In the process, the researchers first dissolve the compound in a small quantity of organic solvent and added to the molten carrier. Researchers then evaporate the solvent to generate the mass. They mill this mass to produce powder at desired particle size ranges.
Generally, 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). Solid dispersion has also been used to produce sustained-release microspheres using tedious methods such as water-in-oil emulsions (disclosed in U.S. Patent 5,556,642).
Generally, 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). Solid dispersion has also been used to produce sustained-release microspheres using tedious methods such as water-in-oil emulsions (disclosed in U.S. Patent 5,556,642).
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.
