Controlling in situ crystallization of pharmaceutical particles within the spray dryer

ABSTRACT

Introduction: Simultaneous solidification and in situ crystallization (or partial crystallization) of droplets within the drying chamber are commonly encountered in the spray drying of pharmaceuticals. The crystallinity developed will determine the functionality of the powder and its stability during storage. This review discusses strategies that can be used to control the in situ crystallization process.

Areas covered: The premise of the strategies discussed focuses on the manipulation of the droplet drying rate relative to the timescale of crystallization. This can be undertaken by the control of the spray drying operation, by the use of volatile materials and by the inclusion of additives. Several predictive approaches for in situ crystallization control and new spray dryer configuration strategies are further discussed.

Expert opinion: Most reports, hitherto, have focused on the crystallinity of the spray dried material or the development of crystallinity during storage. More mechanistic understanding of the in situ crystallization process during spray drying is required to guide product formulation trials. The key challenge will be in adapting the mechanistic approach to the myriad possible formulations in the pharmaceutical industry.

KEYWORDS:

• Spray drying
• crystallization
• pharmaceuticals
• mannitol
• lactose
• amino acids
• drying history
• excipients
• protein stability

Article highlights

• This review discusses the mechanistic approach to control the in-situ crystallization process of pharmaceutical particles in spray dryers.

• Strategies include the manipulation of the spray drying condition, the usage of volatile solvent and the use of additives.

• A list of reports providing mechanistic insights on the in-situ crystallization process is presented.

• New spray drying configurations to control the in-situ crystallization process are introduced.

• The development of mathematical approaches to predict the in-situ crystallization process is reviewed.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.