Drying of Biopharmaceuticals: Recent Developments, New Technologies and Future Direction

Abstract

The dehydration of biopharmaceutical products through dr ying provides numerous benefits, including ease of handling and storage, reduction in transportation costs, and improved stability. Typically, the drying of biotherapeutics is accomplished through freeze-drying, however, the removal of water by lyophilization possesses several drawbacks, including lengthy drying times, low energy efficiency, and the high cost of purchasing and maintaining the equipment. Furthermore, freezedr ying is a batch process which may be challenging to adapt and implement with the recent push for continuous manufacturing. These limitations have led to the search for next-generation drying technologies that can be applied to the manufacture of biotherapeutic products. Several alternative dr ying methods to freeze-dr ying have been developed and implemented in industries outside of pharmaceuticals, such as food and agriculture, and some are at an advanced state. With the aim of applying lessons learned from technologies in various industries, herein, we review several processing technologies with particular emphasis on the advantages and disadvantages of each in comparison to lyophilization and their potential to be adapted and utilized for drying biotherapeutic compounds.

Drying Technologies for the Stability and Bioavailability of Biopharmaceuticals

“…To achieve the desirable stability of proteins in formulations, solid-state dosage form is preferred to liquid-state dosage form, because it can provide a better shelf-life in storage. Numerous drying technologies, including FD, SD, SFD, and SCFD, have been used for dried protein formulations, and they have become an important method for the manufacture, storage, and delivery of protein-based biopharmaceuticals [ 14 , 25 , 26 , 37 ]. However, dried protein formulations still have challenges of stability and further optimization for desirable pharmacokinetic properties [ 3 , 83 ].…”

“…Numerous reviews of drying strategies have been published [ 23 , 24 ]. However, most of these reviews focus on small molecules, and reviews of using drying methods to improve stability or pharmacokinetic properties of therapeutic proteins are relatively few [ 25 , 26 ]. Because proteins are sensitive to environmental stresses, the techniques available for producing dried biopharmaceuticals are limited by factors such as production time, temperature, and various process-related stresses [ 26 ].…”

Accelerated Production of Biopharmaceuticals via Microwave-Assisted Freeze-Drying (MFD)

“…With emerging patient-centered drug manufacturing in the biopharmaceutical industry [ 5 ], small batch sizes create an increasing need for time-saving technologies and flexibility. Hence, numerous new drying technologies and approaches are being developed to speed up the lengthy process [ 1 , 6 , 7 , 8 , 9 ].…”

Electrospinning scale-up and formulation development of PVA nanofibers aiming oral delivery of biopharmaceuticals

“…Biopharmaceutical formulations are more stable in the solid state than in liquid form; in addition, it has many advantages like storage at ambient temperature, longer shelf-life, easier product shipping and the possibility of controlled drug delivery [2]. Currently, the pharmaceutical industry is typically applying freeze drying and spray drying processes in order to obtain solid biopharmaceuticals, however, both technologies have disadvantages [3,4]. Freeze drying is a time-consuming batch technology, has high energy consumption, and the freezing can cause degradation of the biomolecules.…”