Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Amorphous solid dispersions (ASDs) are popular for enhancing the solubility and bioavailability of poorly water-soluble drugs. Various approaches have been employed to produce ASDs and novel techniques are emerging. This review provides an updated overview of manufacturing techniques for preparing ASDs. As physical stability is a critical quality attribute for ASD, the impact of formulation, equipment, and process variables, together with the downstream processing on physical stability of ASDs have been discussed. Selection strategies are proposed to identify suitable manufacturing methods, which may aid in the development of ASDs with satisfactory physical stability.

Download the full (Journal pre-proof) article here: Pharmaceutical amorphous solid dispersion- A review of manufacturing strategies

or continue reading here: Sonal V. Bhujbal, Biplob Mitra, Uday Jain, Yuchuan Gong, Anjali Agrawal, Shyam Karki, Lynne Taylor, Sumit Kumar, Qi Zhou, Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies, Acta Pharmaceutica Sinica B, 2021, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2021.05.014 (https://www.sciencedirect.com/science/article/pii/S2211383521001805)

Commonly used polymers for ASD preparation

Polymer	Tg(°C)	Solubility in solvents
Hydroxypropyl methylcellulose	175‒185	Water, ethanol:dichloromethane (1:1, 2:1), methyl acetate:methanol (1:1)
Hydroxypropyl methylcellulose acetate succinate	100‒110	Caustic water, acetone, methanol, dichloromethane, chloroform
Hydroxypropyl methylcellulose phthalate	133‒137	Water, acetone, ethyl acetate, methyl ethyl ketone, ethanol:dichloromethane (1:1) methanol, dichloromethane, tetrahydrofuran
Polyvinylpyrrolidone	175‒180	Water, acetone, ethanol, methanol, ethyl acetate, methyl ethyl ketone, dichloromethane, tetrahydrofuran
Polyvinylpyrrolidone/vinyl acetate	70‒110	Water, acetone, ethanol, methanol, ethyl acetate, methyl ethyl ketone, dichloromethane, tetrahydrofuran
Polymethacrylates derivatives (Eudragit®-L100, S100)	>150	Water (only L100), acetone, ethanol, methanol, ethanol:dichloromethane (1:1)
Cellulose acetate phthalate	160‒170	Acetone, ethyl acetate, methyl ethyl ketone
Soluplus®	72	water, acetone, ethanol, methanol, dichloromethane

Source: Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Conclusions
A successful development of amorphous solid dispersion formulations depends on three primary factors: active pharmaceutical ingredient properties, stabilizing polymer, and processing technology. Polymers provide the basic and essential foundation for a stable drug amorphization and the process supplies the energy required to transform the system to an amorphous form. The effectiveness of the process is critical to generate, capture, and preserve the amorphous form. The success of these processes is dependent on the processing time and the supersaturation conditions that are being generated during the formation of the solid dispersion.

Despite the discovery of solid dispersions in the early 1960s, the application of the solid dispersion concept to solve solubility challenges had been limited for several decades partly due to the lack of commercially viable processing technologies. However, the past two decades have seen remarkable progress in developing pharmaceutical ASD products as our understanding of ASD systems and their manufacturing technologies have evolved considerably, leading to several commercial products in addition to numerous in development. Spray drying and HME have become the mainstay of ASD preparation in the pharmaceutical industry, while newer methods are constantly being added into the toolbox that promise to improve the quality, productivity, and/or better performance of the products.