Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.442086
Title: Industrial crystallisation and polymorphism of active pharmaceutical ingredients
Author: Colli, Corrado
ISNI:       0000 0001 3560 4208
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2005
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Abstract:
The present work is a study of the crystal forms, crystallisation conditions and structures of some small organic molecules of pharmaceutical interest. The attention is pointed mainly on three features: 1. control of polymorphism; 2. Control of solvates forms; 3. Control of particle the size distribution. Polymorphism: In Chapter 2 are presented two cases of crystallisations where polymorphism problems have shown up: the first case, is a very simple case of a HOI salt where two polymorphs are present, but only one (the thermodynamically stable) is desired. The crystallisation method has been optimised to obtain the pure desired form. The second case presented in Chapter 2, is quite complicated because of the large number of polymorphs and the possibility of Isolating several forms in metastable conditions. The compound, in the present study, has shown four polymorphs and one solvate from toluene. The desired polymorph is called form I, but a certain amount of another polymorph with a very similar stability (called form IB) can be accepted in the final product. The other forms should be absent. All the forms can be isolated in pretty similar conditions, so a lot of attention has to be paid to small details. The solvent mixture is always the same, but the crystallisation conditions are different. Solvates: In Chapter 3 is presented a case where a compound called 'SC HCI' shows 4 solvate forms and one non solvate In this case the optimisation of the precipitation and crystallisation of a compound (it is an intermediate of an API) brought many advantages, both technological and economical. The conditions to constantly obtain the desired non-solvate form have been found. Particle size distribution: in Chapter 4 are presented three cases of crystallisation where the particle size distribution was the main problem. The first is the case of an optimisation of a known process in order to obtain larger crystals, the second is a compound in which the complete synthetic route has been developed including the final crystallisation where the particle size has some specifications (the compound shows up polymorphism problems) and the third case is a process where the particle size has to be very small, but the target has to be reached in a system where the formation of polymorphs and an amorphous phase are possible. Structure solution: Chapter 5 is dedicated to the structure solution by x-ray diffraction. In the first section the structures are solved using the classical technique of single crystal xray diffraction. The second section is dedicated to powder x-ray diffraction. This technique has been used for many years to identify the crystal phases by comparing the patterns obtained. Now the powder x-ray diffraction can be used, in some cases, to solve structures. This opportunity has to be considered very important in the study of polymorphism as many times only one form is thermodynamically stable and single crystals can be grown, but the other polymorphs are metastable and can be obtained only in powder form. In section 2 of chapter 5 are presented some cases where the structure has been studied using powder x-ray diffraction.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.442086  DOI: Not available
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