Spray drying can improve the bioavailability of drugs

Recently, for many drugs administered in fixed doses, it has become extremely important to formulate drugs with good efficacy but poor solubility into controlled-release formulations and to improve their bioavailability. This article focuses on the use of spray-drying technology to produce controlled-release and/or high-bioavailability products, including nanoparticles, microencapsulates, solid amorphous dispersions, and dry emulsions.

Due to the very large specific surface area of the product particles and the extremely high heat transfer coefficient, spray drying is a very rapid drying method. The large specific surface area of the product particles also allows drying to be conducted at moderate to low temperatures. Rapid drying and moderate temperatures make spray drying suitable for heat-sensitive materials. Rapid drying and the resulting rapid stabilization of the material make spray drying particularly well-suited for encapsulation and the production of dry emulsions or amorphous materials. Particle engineering possibilities also encompass powder properties such as aerodynamic particle size, particle geometry, particle size distribution, and powder flow characteristics.

Spray drying of nanoparticles involves drying nanoparticles suspended in a suitable liquid (such as water). Through spray drying, the original particles can be protected while simultaneously acquiring new, more desirable powder properties. That is, the powder exhibits good flow properties and a reduced tendency to generate dust, or it possesses good flow properties and a smaller aerodynamic particle size.

Microencapsulation can be achieved using spray drying and spray condensation processes. The material used for microencapsulation via spray drying is a liquid in which a drug is present in a suspended or dissolved state within the encapsulating material. Suitable solvents include water, alcohol, acetone, and others. An alternative method is spray condensation, in which the coating solution is replaced with a molten coating material. Through spray drying or spray condensation, particle size can be easily adjusted to suit controlled-release formulations and to achieve other desirable powder properties.

Dry emulsions are a variation of microencapsulation technology. In a dry emulsion, the material to be encapsulated consists of microdroplets—that is, an oil solution containing an oil-soluble drug. The material required to produce a dry emulsion via spray drying is an emulsion containing a dissolved solid carrier. After spray drying, the dry emulsion can be re-aggregated to retain the original droplet size, thereby improving the drug’s bioavailability while achieving other desirable powder properties.

Solid amorphous dispersions/solutions can be produced using spray drying. The feedstock used to produce amorphous solid dispersions consists of the drug and a suitable solvent containing stabilizing agents. Suitable solvents include alcohol, acetone, and dichloromethane. Spray-dried amorphous solid dispersions can improve drug bioavailability and enhance drug stability, while also providing other desirable powder properties, such as flowability and direct compression suitability.

Drying

When a drug exhibits thermoplastic properties and has a high affinity for solvents, it becomes difficult to dry the product. For drugs with high solvent affinity, achieving a specific residual solvent content level in the final product requires either higher drying temperatures or lower solvent vapor content in the exhaust gas—a significant challenge, particularly for products that are also thermoplastic. For drugs that are thermoplastic and have a low transition temperature, the effective temperature range for drying is quite limited. Two conflicting factors determine this limited temperature range: the product temperature must be low enough to ensure product stability and prevent caking; at the same time, the drying temperature must be high enough to dry the material within an effective timeframe before the droplets or particles collide with the drying tower wall. To make matters worse, the solvent in the material acts as a plasticizer, lowering the product’s permissible temperature. Incorrect drying conditions can result in very low yields due to material buildup on the tower walls; both excessively low and excessively high drying temperatures can lead to this outcome.

In spray drying, it is crucial to distinguish between the dryer inlet temperature, product temperature, drying temperature, and dryer outlet temperature. In a well-designed co-current spray dryer, the drying temperature and the dryer outlet temperature are the same.

Due to the evaporation of solvents in the product, the product temperature is lower than the dryer outlet temperature, typically by 5–20°C.

The drying of the particles is primarily determined by the spray dryer outlet temperature and the solvent vapor content in the spray dryer exhaust. A higher spray dryer outlet temperature or a lower solvent vapor content in the spray dryer exhaust will both affect product drying. For a fixed spray dryer outlet temperature and drying gas flow rate, lowering the dryer inlet temperature will result in a decrease in feed rate, a decrease in evaporation rate, and a decrease in the solvent vapor content of the spray dryer exhaust. Therefore, the parameters of spray drying must be balanced very carefully; the solution can usually be found within a “window of opportunity.”

The spray drying window may allow drying to proceed at a high yield, but this may simultaneously result in the final product failing to meet the required residual solvent content levels. For many products, effective drying time is of greater importance. When solvent diffusion in the product is constrained, a single-stage dryer cannot achieve effective drying, and in many cases, an additional drying stage must be added.

The thermoplastic properties exhibited by some drugs make them unsuitable for drying in conventional spray dryers. In such cases, low-pressure spray drying can be an alternative. Operating the spray dryer at 0.5–0.7 bar allows for a significant reduction in drying temperature.

Dryer Configurations

The principle behind the PSD is to design a series of units with similar performance but varying capacities, capable of processing batches ranging from a few grams to several metric tons of powder. The consistent performance of PSD units enables a smooth scale-up process from early-stage development to final full-scale production. PSD equipment consists of numerous modules combined to meet specific requirements, regardless of operating temperature, operating pressure, solvent, throughput, or other factors. Consequently, dryers with the same throughput capacity may differ entirely in design, configuration, and physical dimensions. PSD dryers are designed to use hot air or, when drying non-aqueous materials, nitrogen as the drying gas (to eliminate the risk of combustion). They can be used to dry a wide variety of materials based on acetone, dichloromethane, alcohol, and other organic solvents. When organic solvents and nitrogen are used, the dryers typically operate in a closed-loop system to minimize nitrogen loss and prevent the volatilization and leakage of organic solvents.

Summary

Through careful selection of operating parameters, drugs exhibiting thermoplastic properties and solvent affinity can be produced via spray drying. Spray drying offers unparalleled advantages for the production of amorphous materials with controlled-release properties, such as encapsulated formulations, dry emulsions, and/or drugs designed to enhance the efficacy of biopharmaceuticals.