Application of Solid Dispersion Technology in Formulation Development

2020-08-13

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Technology create value, the first platform for drug CMC technology exchange”, the 2020 Drug CMC International Summit Forum was successfully held in Nanjing. Zhou Xiaotang, senior director of Medicilon Biopharmaceutical Preparation Department, shared the “Solid Dispersion Technology in Preparation Research and Development” at the conference The theme report of “Applications of Solid Dispersions” introduces the application and preparation strategies of solid dispersions in detail. This article briefly summarizes the report of Director Zhou Xiaotang. If you have more questions about solid dispersion technology and preparation requirements, please contact us!

Zhou Xiaotang, Senior Director of Medicilon Biopharmaceuticals Department

Solid dispersion is an extremely promising solubilization technology. Preparation of poorly soluble drugs and polymer raw materials into solid dispersions by hot-melt extrusion and spray drying techniques can significantly improve the solubility and dissolution rate of poorly soluble drugs, thereby increasing the bioavailability. This technology is widely used, and the types of solid dispersion drugs currently on the market include:
Listed solid dispersion drugs

Classification of common solid dispersions

Solid solution – The drug is dissolved in a solid carrier in a molecular state to form a homogeneous system. The dispersibility of the drug in the solid solution is often higher than that in the eutectic mixture. Therefore, its dissolution rate is particularly large, and it can be subdivided into displacement type and filling type;
Co-precipitate – a non-crystalline amorphous substance formed by a solid drug and a carrier in an appropriate ratio. The commonly used carrier is a polyhydroxy compound;
Eutectic mixture – The drug and the carrier are fused to form a completely miscible liquid, stirred evenly, and quickly cooled and solidified to become a dispersion. The drug is dispersed in the carrier in the form of microcrystals to become a physical mixture.

Application of solid dispersion

Increase solubility – increase dispersion, high-energy wettability, inhibit crystallization, and improve bioavailability;
Sustained and controlled release preparations – short half-life, sustained release/enteric-coated, low eutectic, microcrystalline;
Increase drug stability – reduce fluidity, high Tg, inhibit recrystallization, and maintain supersaturation;
In addition, solid dispersions have good applications in solidified medicines, dripping pills, medicine taste masking technology and patent evasion.

Common preparation methods

—	Advantages	Disadvantages
Spray drying	High speed Adjustable particle size Continuous process Strong mixing	solvent remains high cost
Freeze drying	Mild conditions No high temperature	high cost solvent remains
Supercritical	Mild conditions No high temperature	high cost Solubility
Hot melt extrusion	Solvent free Dust-free Continuous process Small footprint Good reproducibility low cost	Pay attention to temperature Post-processing

Techniques for preparing solid dispersions

Hot melt extrusion method: In the hot melt extrusion process, after the mixture of API, carrier and excipient enters the extruder, the material is first melted under the heating of the extruder barrel and strong shearing force, and then dispersed, distributed and mixed Finally, the material is extruded from the die by the extruder screw extrusion. Technology for preparing solid dispersion-hot melt extrusion method

Spray drying method:After filtering and heating, the air enters the air distributor on the top of the dryer, and the hot air enters the drying chamber evenly in a spiral shape. The material liquid passes through the high-speed centrifugal atomizer on the top of the tower, and (rotating) sprays into very fine misty liquid beads, which can be dried into finished products in a very short time in cocurrent contact with hot air.Technology for preparing solid dispersion-spray drying method

Medicilon’s preparation department can provide the following services: