ZHANG Xiaoyang^a, YING Zehua^a, GUO Shubo^a, LI Wenlong^{a, b}

(a. College of Pharmaceutical Engineering of Traditional Chinese Medicine,b. Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China)

Abstrac

Significance Drug solubilization is an essential step for orally administered medications to be absorbed systemically. Unfortunately,many drugs have poor water solubility, which severely limits their clinical applications. During drug Research & Development,various methods have been tried to overcome the poor water solubility of drug candidates, including salt formation, micritization,solid-lipid nanoparticles, nanosuspensions, and solid dispersions (SDs). Among them, SDs technology stands out for the advantages of simplicity, rapidity, and maturity, making it oone of the most successful strategies for improving the dissolution properties of insoluble drugs. SDs. Hence, SDs have emerged as a hot research topic in the past decade.

Progress So far, many techniques have emerged for the preparation of SDs, which are derived from the following methods, including the melting method, solvent method, melt-solvent method, and milling-based method. Among them, melt-based hot melt extrusion technology (HME) has gained prominence as a solvent-free, commercially scalable method for various drug delivery systems. Additionally, spray drying technology known for its extremely fast solvent removal efficiencies and good scale-up capabilities, has become the most popular solvent method. The fluidized bed drying method stands out for its ability to prepare SDs with both good flowability and dissolution properties. Furthermore, 3D printing technology offers the advantages in personalization and dosage form customization for pharmaceutical production. Despite the availability of these techniques, the selection of apprpriate preparation techniques for SDs remains a challenge due to the complex and variable physicochemical properties of APIs and polymers as well as the lack of in-depth knowledge of the preparation techniques. Although many drug products based on SDs technology have been successfully marketed since 1989, the current quality control of SDs was still limited to the solid state, drug -polymer interactions, and dissolution, neglecting the crucial powder properties of SDs. Notably, SDs serve as formulation intermediates and need further processing into tablets, pills, capsules, and granules for convenient consumption. The powder properties of SDs play a pivotal role in ensuring the smoothness of downstream processing and the overall quality of the final products.

Conclusions and Prospects It was the prerequisite for the correct selection of preparation techniques to have a deeper understanding of the application scenarios, advantages, and limitations of various preparation techniques. Furthermore, the significance of the physicochemical properties of drugs and polymers in selecting suitable preparation strategies should not be overlooked. These properties are related to the thermal and physical stability of the final product and should be thoroughly reviewed in the future.Although many techniques have been applied to prepare SDs, several challenges persist. Many issues such as the use of toxic solvents and the possible risk of thermal degradation of the drug still need careful addressing. In addition, the current choice of commercially viable SDs preparation techniques is still very limited. Future research endeavors should try to develop simpler, more efficient, and scalable techniques for the SDs preparation. In terms of quality control of SDs, in addition to examining the solid state, drug-polymer interactions, and dissolution, researchers are required to conduct accurate and comprehensive assessments of the powder chemistry properties of SDs. The creation of SDs with both excellent flowability and dissolution properties undoubtedly holds the promise to significantly contribute to the successful commercialization of SDs products.

Keywords: solid dispersion; hot melt extrusion; melt condensation; three-dimensional printing; fluidized bed; supercritical fluids; electrospinning

Get Citation:ZHANG X Y, YING Z H, GUO S B et al. Research progress on the preparation techniques and quality control of solid dispersions[J]. China Powder Science and Technology, 2024, 30(2): 96-112.

DOI:10.13732 / j.issn.1008-5548.2024.02.009

CLC No: TB4; R943                   Type Code:A

Serial No:1008-5548(2024)02-0096-17