Bioavailability Enhancement: When to Use Hot-Melt Extrusion versus Spray Drying - Pharmaceutical Technology

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Bioavailability Enhancement: When to Use Hot-Melt Extrusion versus Spray Drying
Enhancing bioavailability can be achieved through hot-melt extrusion or spray drying. The drug product's API properties and stage of development are important factors to consider when deciding which technique to use.

Pharmaceutical Technology
Volume 36, Issue 8, pp. 44-45

Advantages and disadvantages of each technique

PharmTech: What are the advantages and disadvantages of using HME compared with spray drying to produce the amorphous solid dispersion?

Bend Research: HME has two primary advantages. First, no solvents are used, so solvent cost and recovery are not a factor in cost-of-goods or environmental health and safety considerations. Second, the equipment footprint for HME is relatively small when the process is scaled up.

The primary disadvantage of HME is that the compound must be melted or dissolved in molten polymer at high temperatures. Thus, it is less applicable to compounds with higher melting temperatures or those that are thermally labile. This disadvantage can be partially remedied by including nonvolatile and volatile plasticizers in the formulation, which lower the temperatures required to produce an amorphous dispersion. Because an ideal amorphous dispersion is homogeneous at the molecular level, a second disadvantage is that the homogeneity of the final dispersion can be affected by process parameters such as temperature, screw configuration, screw speed, and feed rates; this aspect, combined with the relatively large minimum batch size, results in cost and risk during early development.

PharmTech: What are the advantages/disadvantages of using spray drying compared with HME to the amorphous solid dispersion?

Bend Research: Spray drying offers the following advantages: it is applicable to a broader chemical space for the API and types of dispersion polymers that can be used (due to dissolution of the API in a volatile organic solvent); it does not expose the API to excessive heat during manufacture of the amorphous dispersion; and it can be scaled down, requiring smaller quantities of API during formulation screening.

Spray drying has a few disadvantages as well: solvents are used and must be recovered, equipment footprints are larger, and capital and operating costs are higher. These considerations must be taken into account when designing later-stage or commercial processes and facilities, but they are not insurmountable—as evidenced by successful operation of Hovione's PSD-4 and PSD-5 spray-drying facilities and the fact that spray drying is used extensively outside of the pharmaceutical industry at large scales.

Achieving desired bioavailability

PharmTech: Can you be specific in terms of achieving desired bioavailability/solubility of the resulting product, stability of the resulting product, the ease and/or scalability of the manufacturing process, and other process conditions that are important in deciding which approach to use?

Bend Research: As mentioned previously, both spray drying and HME can be used effectively to manufacture amorphous dispersions. A formulation produced by either process would be expected to yield similar bioavailability and physical stability as long as both processes yield a homogeneous amorphous dispersion with appropriate final-powder particle size, which generally requires milling for HME. If either of the processes fails to produce a homogeneous amorphous dispersion, the resulting formulation will likely underperform. This situation is most common when a compound fails to completely dissolve during the HME process due to either the high melting temperature of the compound, or the low solubility of the compound in the molten polymer, resulting in crystallization or phase separation when the melt cools.

Spray drying and HME are readily scaled. Commercial-scale equipment is available at many pharmaceutical organizations and several contract research organizations.


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