E-mail us

Development and Production Application Case Study of Amorphous Solid Dispersions: Spray Drying

In the previous article, we introduced the application of hot-melt extrusion technology in the development of amorphous solid dispersions in pharmaceutical formulation. Spray drying (SD) is another common method for preparing amorphous solid dispersions. It involves dissolving solid substances including API, polymers, and surfactants into a solvent, and then using a spray drying device to atomize the solution, allowing it to come into contact with heated gas, rapidly evaporating and drying to obtain amorphous solids. Spray drying methods have been widely used in the development of poorly soluble drug formulations due to the relatively mature process from small-scale testing to commercial production, which fully complies with the requirements of Good Manufacturing Practice (GMP). Table 1 lists some drugs that have been marketed using spray drying technology to prepare amorphous solid dispersions.

crystalpharmatech-2023913-80.jpgTable 1: Oral formulations on the market using spray drying technology (examples)

The schematic diagram of a spray drying system is shown in Figure 1. The spray drying process mainly includes:


Figure 1: Schematic diagram of the spray drying process

crystalpharmatech-2023913-82.pngFigure 2: Spray Dryer Used by Crystal Pharmaceuticals

(Buchi B-290;GEA PSD-1)

Advantages vs. Disadvantages

Advantages and Disadvantages of Spray Drying in Amorphous Solid Dispersion (ASD) Preparation:



(Note: These disadvantages are relative, and ongoing improvements in spray drying equipment and processes, along with continuous technological innovations, are better managing these challenges. Due to its applicability to a wide range of drug molecules and its inherent advantages, spray drying has become one of the most widely adopted methods for preparing amorphous solid dispersions.)

Case Study



the structure of Deucravacitinib

In this case study, Deucravacitinib, which was approved in the United States in September 2022 for the treatment of moderate to severe plaque psoriasis in adult patients suitable for systemic therapy or phototherapy, is discussed. It is the world's first approved oral selective tyrosine kinase 2 (TYK2) modulator, marketed under the brand name Sotyktu, available in a 6 mg oral tablet formulation. The innovator company, Bausch Health, predicts peak sales of up to $4 billion for this drug.

Deucravacitinib is classified as a BCS Class II drug, which means it has low solubility but high permeability. Its solubility is pH-dependent, with higher pH levels resulting in lower solubility. For example, at pH 1.05, the solubility of the free base crystal form is greater than 3 mg/mL, while at pH 6.5, it is only 0.009 mg/mL. To address this pH-dependent solubility and improve drug performance, the innovator company conducted research into various salt forms and crystalline polymorphs. They discovered that the hydrochloride salt form exhibited higher bioavailability and reduced pH dependence compared to the free base and other salt forms. In dogs, the hydrochloride salt form had an average bioavailability 60% higher than the free base. Consequently, the hydrochloride salt form was chosen for the early clinical trials, formulated as capsules.

However, the hydrochloride salt of Deucravacitinib was prone to racemization, which required the capsules to be stored under refrigeration for extended periods to prevent conversion to the free base during storage. This significantly increased the drug storage costs and inconvenience. To enable long-term storage at room temperature while maintaining high bioavailability and low pH dependence, a new formulation strategy was implemented during Phase III clinical trials—amorphous solid dispersion (ASD). In this method, the free base crystal form of the drug was mixed with hydroxypropyl cellulose acetate succinate (HPMCAS) in a solvent mixture of acetone and water to form a solution. The solution was then spray-dried to create an ASD, which was subsequently mixed with excipients, granulated, milled, blended, and compressed into final products—film-coated immediate-release tablets. This formulation achieved an absolute bioavailability of up to 99%.

In this case, the innovator company initially selected the hydrochloride salt as the active form due to its enhanced bioavailability and reduced pH dependence. However, concerns about racemization and the need for refrigeration during storage led to further optimization of both the solid form of the drug and the formulation strategy. Ultimately, the free base crystal form was chosen as the active pharmaceutical ingredient (API), and an amorphous solid dispersion (ASD) was developed using spray drying to significantly improve solubility and bioavailability while addressing the pH dependence issue. This optimized formulation allowed for long-term storage at room temperature and achieved high bioavailability.

Crystal Pharmaceutical's Advantages in Solid Dispersion (SD)

Crystal Pharmaceutical's core team possesses backgrounds in polymer materials, chemical engineering, and mechanics, guided by principles of rheology and engineering. They have extensive experience in both fundamental theory and large-scale processes, and have led formulation teams to successfully bring blockbuster SD drugs to market. Leveraging our world-class process equipment and analytical instruments for small- to large-scale processes, we have the confidence to assist global innovative pharmaceutical companies in providing high-quality drugs based on spray drying technology.

Related Updates in Crystal Pharmatech

Contact Us
bd_global@crystalpharmatech.com +1-609-604-8303
Suite 500-B, 3000 Eastpark Blvd, Cranbury, New Jersey 08512, USA
6800 Kitimat Rd, Unit 1, Mississauga, Ontario, Canada L5N 5M1
Suite B4-101, Biobay, 218 Xinghu Street, Suzhou Industrial Park, Suzhou, China, 215123
Suite 500-B, 3000 Eastpark Blvd, Cranbury, New Jersey 08512, USA
bd_global@crystalpharmatech.com +1-609-604-8303