Common Solid Dispersion Preparation Methods (P3)

There are numerous methods to enhance the solubility of APIs, including the preparation of nano-sized particles, salt formation, and solid dispersion (SD) systems. Among these techniques, SD is considered a promising option due to its ability to improve solubility. The choice of SD preparation method depends on the physicochemical properties of the API, carrier, dosage form, and available equipment.

Introduction

Solid Dispersion – SD is a widely used pharmaceutical formulation technique to enhance the dissolution rate and oral bioavailability cof poorly water-soluble drugs. Essentially, SD is a dispersion of a drug in a solid carrier in a solid state, creating a system with a larger surface area, thereby increasing the dissolution rate and drug absorption. There are various SD preparation methods, each with its own advantages and disadvantages.

Common Solid Dispersion Preparation Methods

Here are some common SD preparation methods:

Fusion method: This is the simplest and most economical method, in which the drug and carrier are mixed thoroughly and heated until completely melted at a temperature slightly above the eutectic mixture point. The mixture is then rapidly cooled in an ice bath and ground into fine particles. The advantage of this method is its simplicity and the absence of solvent use. However, this method is not suitable for drugs that are easily degraded at high temperatures.
Hot-melt extrusion method: A mixture of drug, carrier, and plasticizer is passed through an extruder at high temperature. The advantages of this method include the absence of solvent use, control over the shape of the product, and no need to grind the final product. The disadvantage is that this method is not suitable for heat-sensitive drugs due to the high temperature during extrusion.
Melt Agglomeration: This is a solid dispersion preparation technique using a binder as a carrier. There are two ways to create SD using this method. The first is to spray the drug dispersed onto the melted binder, and the second is to melt a mixture of binder, drug, and other excipients at a temperature higher than the melting point of the binder. This method is similar to the fusion method but uses a binder instead of a conventional carrier.

Solvent evaporation method: This method is suitable for heat-sensitive drugs as the drug and carrier are dissolved in a volatile solvent, and then the solvent is removed by evaporation. The advantage of this method is that it avoids the degradation of the drug and carrier due to low evaporation temperature. The disadvantage is that this method requires the use of a solvent, which may leave solvent residues in the final product.
Spray drying method: A solution of drug and carrier is sprayed into a drying chamber with a hot air stream. The solvent evaporates rapidly, forming dry SD particles. The advantages of this method are the production of SD with uniform particle size and good control. The disadvantages are the high cost of equipment and the possibility of drug degradation due to the drying temperature.

Các phương pháp bào chế hệ phân tán rắn phổ biến

In addition to traditional preparation methods, researchers are currently investigating and developing new SD preparation methods such as using supercritical fluid technology. Supercritical fluid technology uses CO2 in a supercritical state as a solvent or anti-solvent to create SD with ultrafine particle size, enhancing drug solubility and bioavailability.

In conclusion, the choice of suitable SD preparation method depends on the properties of the drug, carrier, and the requirements of the dosage form. The research and development of new, more effective, and safer SD preparation methods is ongoing