Polymorphism in the Pharmaceutical Industry

Rolf Hilfiker , Markus von Raumer 지음

Wiley-VCH 2018년 12월 14일 출간

작품소개

책소개

"Polymorphism in the Pharmaceutical Industry - Solid Form and Drug Development" highlights the relevance of polymorphism in modern pharmaceutical chemistry, with a focus on quality by design (QbD) concepts. It covers all important issues by way of case studies, ranging from properties and crystallization, via thermodynamics, analytics and theoretical modelling right up to patent issues. As such, the book underscores the importance of solid-state chemistry within chemical and pharmaceutical development. It emphasizes why solid-state issues are important, the approaches needed to avoid problems and the opportunities offered by solid-state properties. The authors include true polymorphs as well as solvates and hydrates, while providing information on physicochemical properties, crystallization thermodynamics, quantum-mechanical modelling, and up-scaling. Important analytical tools to characterize solid-state forms and to quantify mixtures are summarized, and case studies on solid-state development processes in industry are also provided. Written by acknowledged experts in the field, this is a high-quality reference for researchers, project managers and quality assurance managers in pharmaceutical, agrochemical and fine chemical companies as well as for academics and newcomers to organic solid-state chemistry.

목차

Preface to the Second Edition xv 1 Solid State and Polymorphism of the Drug Substance in the Context of Quality by Design and ICH Guidelines Q8 Q12 1Markus von Raumer and Rolf Hilfiker 1.1 Introduction 1 1.2 A Short Introduction to Polymorphism and Solid-State Development 1 1.3 A Short Introduction to Quality by Design (QbD) 3 1.4 The Solid State in the Context of Pharmaceutical Development 7 1.4.1 Typical Drug Discovery and Development 7 1.4.2 The Solid State at the Interface of Drug Substance and Drug Product 10 1.4.3 Biopharmaceutics and Bioavailability of Solids 11 1.4.4 Pharmaceutical Quality Assessment 14 1.5 Solid-State Development at Various Stages of the Pharmaceutical Development Process 15 1.5.1 The Solid State in the Discovery Phase 16 1.5.2 Salt and Co-crystal Screening and Selection 16 1.5.3 Polymorph Screening, Polymorph Landscape, and Polymorph Transformations 17 1.5.4 Crystallization and Downstream Processes 20 1.5.5 Formulation 21 1.5.6 AnalyticalMethods for Characterization and Physical Purity Determination 22 1.6 Conclusions 23 References 23 2 Alternative Solid Forms: Salts 31P.H. Stahl, Bertrand Sutter, Arnaud Grandeury and Michael Mutz 2.1 Introduction 31 2.2 Salt Formation and Polymorphism in Pharmaceutical Development 31 2.3 Target Properties of Active Substances for Drug Products 33 2.3.1 Injectables 34 2.3.2 Solid Dosage Forms 35 2.3.3 Dosage Forms for Other Routes of Application 36 2.3.3.1 Inhalation 36 2.3.3.2 Topical Products and Transdermal Route 36 2.4 The Basics of Salt Formation 37 2.4.1 Dissociation Constant 37 2.4.2 Ionization and pH 39 2.4.3 Solubility 40 2.4.4 Disproportionation 43 2.5 Approaches to Salt Preparation and Characterization 45 2.5.1 Initial

작가정보

저자(글) Rolf Hilfiker

Rolf Hilfiker is vice president and head of the department Solid-State Development at Solvias AG in Kaiseraugst, Switzerland. He obtained his PhD in physical chemistry from Basel University (Switzerland) and then did postdoctoral work at Stony Brook University (New York). He returned to Basel University as a research fellow and then moved to Ciba-Geigy (now Novartis) in Basel. In 1997 he became head of the Stability & Kinetics group at Novartis. In 1999 he participated in a management buyout to form Solvias AG. He has taught physical chemistry in New York and Basel, as well as numerous courses in solid-state development in Europe, Asia, and the US. Markus von Raumer is director and group leader of Preformulation and Preclinical Galenics at Idorsia Pharmaceuticals Ltd. in Allschwil, Switzerland. He obtained his PhD in physical chemistry from the University of Fribourg (Switzerland) and then did postdoctoral work in the field of mass spectrometry at the University of Warwick (UK). In 1997 he became head of laboratory of Physical Chemistry at Novartis in Basel, Switzerland. Two years later he moved to Solvias AG in Basel where he was project manager for Solid-State Development until 2008. He then joined Actelion Pharmaceuticals Ltd. in Allschwil where he built up and led the Material Science lab until 2017.

저자(글) Markus von Raumer