Wet granulation is a common industrial operation for particle size enlargement, which traditionally has been performed in batch-based operations. However, the potential advantages of continuous granulation such as improved quality, rapid API sparing development and greater flexibility have drawn attention to this technology. One of the common equipment evaluated to perform continuous granulation is the twin-screw granulator (TSG). The advantage of this equipment is the flexibility offered from

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... he high number of possible working environments achieved by changing different sections of the screw assembly, different segment geometries or feed port locations. However, the current state of art of this technology does not yet allow the implementation into the pharmaceutical process. The introduction of this technology requires an increased knowledge of the granules properties as well as the acceptable working limits of the TSG equipment. In this thesis, both issues have been addressed. On one side, a homogeneity factor to transform particle size distributions in a percentage easing the creation of design workspaces was developed. Also, the verification of the channel fill methodology to an 11 mm twin screw granulator and its relationship with another iv process parameters was explored. Furthermore, a method to use microencapsulated sensors (CAMES) whose rupture is directly dependant on their experienced shear stress was developed for first time for TSG. On the other side, an algorithm to extract selected parts from inside the granule was developed and applied to granules obtained by both batch and continuous. In addition, the effect of the liquid availability and drying effect in the formation of granules was studied obtaining significant morphological differences depending on the temperature. Furthermore, it was found that nuclei obtained a different liquid to solid ratio were similar in size but different in number which suggest that the granules size is directly dependant on the liquid availability. v Acknowledgements This PhD has been a long journey that fortunately I didn't make alone. I am so grateful to all the people who have helped me in a way or another to complete it. First of all, I want to thank both of my supervisors: Prof. Gavin Halbert and Dr. Dimitrios Lamprou. I am so pleased to have worked with both of them. They always helped me to "go for it" meanwhile they gave me the freedom and confidence necessary to finish this PhD. Also more a friend than a supervisor, I want to thank to Dr. Robertson for being a daily support in every aspect with our coffee gatherings. A very special thanks to Dr. Thomas McGlone who is not only the best lab manager I had the opportunity to work with, he is also a great friend. I also want to thank to Dr. Deborah Bowering, Dr. Tariq Islam and Dr. Elke Prassad for always having a smile when they provided me training and support. I cannot forget to thank two of my PhD fellows: Fred Doerr and Lauren Connor who performed the NanoCT and STA analysis and with whom I really enjoyed to work with. Also, Bilal Ahmed for proofreading my work and avoid my Spanglish. In the computational part, I would like to thank Dr. Javier Cardona and Dr. Tony Vassileiou for helping me to go a step further with my codes and even more important for being great friends. A very special gratitude goes out to all down at CMAC for helping and providing the funding for my work. Also, I would like to thank R&D Platform Technology & Science GSK group in Ware and vi especially to Richard Elks and Lee Gorringe for the opportunity of working with them during my placement. Less related to my work but essential to my PhD journey, I want to thank my full coffee team: Alice, Arabella, Bruce and SJ with occasional appearances of Antonia and Mike. You have been my main reason to make it at a reasonable hour in the morning. Also, I am very happy to be part of the "Friday pints group" because in many ways you have made all these years full of crazy fun and good conversations. A special remark goes for three of my favourite drama people: Carla, Georgia and Scott. There are some people who supported me all the way here. First of all, I want to thank my friends from Santiago (Lu, Ade, Quinte, Roi, Colo, Dibua, Mac y Lara). I hope we keep meeting for many years to come. Also, my friends from Allariz (Lore, Brais, Pau and Manza) who always 'confian' even if when I don't do it. A special remark goes to Maro and Vado who have been one of my main constant supports during this PhD never mind the 2500 km in the middle. Special mention to Rosa, my chemistry teacher who was the first one to introduce me her love for science. And finally, last by no means least, to my family and especially to my parents who have been always a source of inspiration, love and support. I doubt you can be luckier than to be raised in a home so full of laughter and joy. I am quite certain I owe you any achievement I make, os quiero muchisimo. Also, to my primi who is more a sister than a cousin. Finally to Paul, who is the one who gave me the biggest encouragement in this PhD and to be fair, in my life in general, you are okay+, Polpol.