Classification of solid dispersion systems (P2)

Solid dispersion is a system consisting of a hydrophobic drug dispersed in at least one hydrophilic carrier, which increases the surface area of ​​the drug and improves the dissolution rate (and possibly solubility) of the drug. Solid dispersions can be classified based on the carrier or structure.

1. Classification of solid dispersion systems based on carriers

• Generation I: Drug delivery systems with crystalline structures (mannitol, dextrose, fructose) are used. These are combined with the drug in one of two ways: as a physical mixture or as a eutectic mixture of the two components, which increases the solubility of the drug. However, these mixtures are thermodynamically unstable.
• Generation II: Generation 2 overcomes the disadvantages of generation 1 by using amorphous polymer carriers (including HPMC, cyclodextrin (CDs), PVP, PEG, etc.). This system includes drugs dispersed in polymer carriers and reaching a supersaturated state. The smaller particle size, improved wettability, and increased water solubility of the drug are all benefits of this system.
• Generation III: Drug delivery systems with carriers that are mixtures of surfactants and polymers or mixtures of surfactants/polymers are the most effective. Surfactants and other hydrophilic carriers are adsorbed onto the solid surface, reducing the surface tension of the two solid-liquid phases. They play a crucial role in wetting and dispersing, significantly improving the solubility of the drug. The most commonly used surfactants are Gelucire 44/14 or 50/13, Compritol 888 ATO, Poloxamer 407 or 188 (Pluronic F117 or F68), …

  

2. Classification of solid dispersions based on structure

The structure is an eutectic mixture

It is a mixture with a fixed ratio of components so that the melting temperature of the mixture is lowest compared to the melting temperature of each component in the mixture as well as the melting temperature of the mixture with different proportions. Eutectic mixtures have the advantage of very small particle size of the components (microcrystalline structure) and the lowest melting temperature of the mixture. Therefore, it is used to increase the stability and solubility of the drug.

The structure is a solid solution

A solid solution is a dispersion in which the particles of solids are of atomic or molecular sizes. For example, solid particles of a hydrophobic drug are evenly dispersed in solid particles of a hydrophilic carrier. There are two main types of solid solutions: continuous and discontinuous. These are classified based on the miscibility and molecular size of the components that make up the solid solution:

– Continuous solid solution: The components in this system can and will dissolve completely in each other in all proportions. The binding force between them is stronger than the binding force in each component when standing alone. This improves the physical properties of the mixture, including the solubility and dissolution rate of the drug, making it easier for the body to absorb the drug.

– Discontinuous solid solution: is a system in which the solubility of the components is limited, meaning that they cannot dissolve into each other completely but only to a certain extent. This results in a limited amount of each component being able to dissolve in the solid solvent. Discontinuous solid solutions are divided into two types:

• Substitutional solid solutions, figure A: Solute molecules replace solvent molecules in the crystal lattice. That is, solute molecules occupy the positions that would otherwise belong to solvent molecules.
• Interstitial solid solutions, figure B: The solute molecules do not replace the solvent molecules, but rather fill the spaces between the solvent molecules in the crystal lattice. This usually occurs when the solute molecules are much smaller than the solvent molecules.

  

Glass solution or glass suspension

A solid dispersion system in which the drug is completely dissolved or dispersed in a solvent that exists in a “glass” state. The glass state is defined by two characteristics: transparency and brittleness. These properties are observed in both solutions and suspensions below the glass transition temperature (Tg).

In summary, the division of solid dispersion systems according to carrier or structure is an effective method for dispersing drugs into carriers to increase contact areas and binding energies among drug molecules – carriers – and solvents (over than that between drug mocules – drug mocules). This approach improves solubility and solubility of drugs.

Tham khảo:
1. Application of Solid Dispersion in Improving Solubility (P1)

2. https://www.mdpi.com/1999-4923/11/3/132