Controlling solid-state and particle properties of pharmaceutical materials by spray drying

Spray drying is a continuous manufacturing technique which has added significant value to the pharmaceutical industry. The chapters herein highlight various advantageous applications of spray drying beyond commonly used applications including formulating amorphous solid dispersions (ASDs) and particles for pulmonary delivery. In this thesis, spray drying has been applied to control the solid-state and particle properties of pharmaceutical materials. This is made feasible through the particle engineering capabilities of spray drying governed by variable input process parameters.

Chapter 1, the introduction chapter, outlines an overview of the theory related to the topics discussed herein. This chapter aims to support the succeeding chapters by providing more background to the explored concepts and pplications. A section of this chapter was adapted from our review paper published in the European Journal of Pharmaceutical Sciences (DOI: 10.1016/j.ejps.2024.106931).

Chapter 2, the first experimental chapter, focuses on spray drying the active pharmaceutical ingredient (API), carbamazepine (CBZ). In this work spray drying is applied to control the polymorphic form of the spray dried powder produced. Currently, research in the areas of polymorphic control by spray drying has been less investigated. In this work. a pure, metastable polymorphic form of CBZ was isolated in a controlled manner. This chapter has been published in the Royal Society of Chemistry Journal CrystEngComm (DOI: 10.1039/D2CE01041K).

Chapter 3 builds on the investigation in chapter 2 and applied the same spray drying technique of varying the atomising gas flowrate parameter to another API, chlorothiazide (CTZ). The chapter further highlights the control offered by spray drying polymorphic APIs as a novel polymorphic form of CTZ was isolated. The last polymorph of an API to be discovered by spray drying was in 1982. The polymorphic form obtained was the fourth polymorphic form of CTZ and has not been isolated by another technique. Chapters 2 and 3 demonstrate how spray drying can both control and lead to the discovery of polymorphic forms of pharmaceutical materials. Chapter 3 has been accepted for publication by the Royal Society of Chemistry (RSC) Pharmaceutics Journal.

Chapter 4 investigated another application of spray drying; a fixed dose combination co-amorphous system of CBZ and CTZ was spray dried. Co-amorphous systems, although advantageous in terms of solubility, pose a great challenge in terms of stability. As the stability of metastable polymorphic forms of CBZ and CTZ were controlled using the spray drying method outlined in chapters 2 and 3, in this chapter spray drying is applied to stabilise a co-amorphous mixture of the two APIs. This chapter demonstrated that a spray dried co?amorphous system consisting of the two APIs can be stabilised at accelerated stability conditions for three months. This chapter has been published in the RSC Pharmaceutics Journal.

Chapter 5 outlines a collaborative project carried out at Johnson and Johnson (J&J) Innovative Medicine in Beerse, Belgium. This project investigated an additional application of spray drying pharmaceutical materials with the addition of comparing conventional spray drying with an emerging spray drying technique, electrostatic spray drying. The aim was to produce spray dried powder that can be stored at room temperature to be reconstituted with the same properties as the original suspensions mitigating the need for cold chain storage. In this work two pharmaceutical suspensions of two different APIs were spray dried. One API is a commercially available API, indomethacin (IND) and the other is a J&J API, referred to as API D. This chapter shows that spray drying can be applied to produce powder that can remain stable at room temperature for one month and can be reconstituted with the same properties as the original suspensions. This chapter has been submitted to Powder Technology.

Chapter 6 is the conclusion chapter which ties the conclusions of each of the experimental chapters together. Chapter 7 is the final chapter herein which outlines the future prospectives of the work in this thesis.