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Pharmaceutical cocrystals: formation mechanisms, solubility behaviour and solid-state properties
Luleå tekniska universitet, Institutionen för hälsovetenskap, Medicinsk vetenskap.ORCID-id: 0000-0002-6050-0432
2012 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

The primary aim of pharmaceutical materials engineering is the successful formulation and process development of pharmaceutical products. The diversity of solid forms available offers attractive opportunities for tailoring material properties. In this context, pharmaceutical cocrystals, multicomponent crystalline materials with definite stoichiometries often stabilised by hydrogen bonding, have recently emerged as interesting alternative solid forms with potential for improving the physical and biopharmaceutical properties of a drug substance. There are, however, gaps in our understanding of the screening, scale-up and formulation operations required for effective use of cocrystals in drug product development. The objective of this thesis was to improve fundamental understanding of the formation mechanisms, solution behaviour and solid-state properties of pharmaceutical cocrystals. The solution chemistry and solubility behaviour of a diverse set of cocrystals were studied. It was found that the thermodynamic stability regions of the cocrystals and their components were defined by the phase solubility diagrams. Spray drying was introduced as a new method of preparing cocrystals; the formation mechanisms are illustrated. The cocrystals were more soluble than the respective drugs alone and the solubility-pH profiles were able to be predicted by mathematical models using a eutectic point determination approach. The cocrystal solubility was pH-dependent and could be engineered by the choice of coformers; this is valuable information for designing robust formulations. The solubility advantage of cocrystals was retained by the use of excipients that imparted kinetic and thermodynamic stability. The retention of drug-coformer association in processed cocrystals has been revealed, introducing a novel concept with potential implications for solid dosage form development. The final study demonstrated that the structure of the crystals and the particle engineering processes affected the solidstate and bulk particle properties of the cocrystals.This thesis contributes to the field of pharmaceutical science by advancing our understanding of crystallization processes and formulation development, thus enabling pharmaceutical cocrystals into drug products.

Ort, förlag, år, upplaga, sidor
Luleå: Luleå tekniska universitet, 2012. , s. 77
Serie
Doctoral thesis / Luleå University of Technology 1 jan 1997 → …, ISSN 1402-1544
Nyckelord [en]
Cocrystal, formation, solubility, pH, dissolution, surface properties, Pharmaceutics, Pharmacy
Nyckelord [sv]
Farmaci
Nationell ämneskategori
Annan hälsovetenskap
Forskningsämne
Hälsovetenskap
Identifikatorer
URN: urn:nbn:se:ltu:diva-26478Lokalt ID: e70f8030-e420-4b27-98f2-953356eff33aISBN: 978-91-7439-421-4 (tryckt)OAI: oai:DiVA.org:ltu-26478DiVA, id: diva2:999640
Anmärkning
Godkänd; 2012; 20120322 (amjalh); DISPUTATION Opponent: Professor emeritus Peter York, School of Pharmacy, University of Bradford, United Kingdom Ordförande: Professor Yelverton Tegner, Institutionen för Hälsovetenskap, Luleå tekniska universitet Tid: Torsdag den 26 april 2012, kl. 10.00 Plats: C305, Luleå tekniska universitetTillgänglig från: 2016-09-30 Skapad: 2016-09-30 Senast uppdaterad: 2018-05-31Bibliografiskt granskad

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