Polymorphism, Salts & Crystallization Brochure

Polymorphism, Salts & CrystallizationAn Integrated Approach to Solid-State Development Amazing where you can go-1-Introduction: Solid-State DevelopmentThe majority of drugs are administered as solids. This means that apart from the molecular structure of the active ingredient, solid-state properties significantly influence the performance of the final product.Often new substances with pharmaceutical ac-tivity are weak acids or bases or may have sub-optimal solid-state properties. In such cases it may be preferable to develop the drug as a salt or co-crystal form. When only amorphous forms are known, specially designed crystallization screenings can help to find crystalline candidates, often improving the chemical purity and stability.Selection of the best available crystalline candi-date should be based on the following physical and chemical parameters:• Stability (chemical and physical) • Solubility/dissolution/bioavailability • Hygroscopicity• Melting point • Polymorph landscape complexity and polymorphic transformations• Number of polymorphs • Processability • Ease of preparation In addition to its impact on chemical and physical properties, salt and co-crystal forma-tion is also relevant for intellectual property considerations because solids with superior properties can be patent protected. -2-At Solvias......we support you every step of the waySolid Form SelectionIn a well-designed salt/co-crystal screening process, the optimal salt/co-crystal will be chosen quickly, based on parameters such as solubility, hygroscopicity, crystallinity, stability, and ease of production.Solvias solid-state development programs provide you…Polymorph Screening and CharacterizationOptimizing the experimental effort in polymor-phism screening requires using the appropriate number of precisely designed experiments to address the specific questions and stage of de-velopment of the drug substance under study. Our polymorphism screening strategy has been optimized through decades of experience and is readily tailored to our customers’ needs. Characterization of relevant polymorph prop-erties provides the understanding needed for subsequent substance development, including crystallization process scale-up.…with time and money saving solutions…Crystallization ScreeningTogether, experience and technology work to provide effective screening for the crystalli-zation of amorphous and hard-to-crystallize substances.High-Throughput ScreeningOur robust technology provides the maximum information with the minimum amount of your valuable drug substance.Polymorphic Purity/Amorphous ContentAccurate and sensitive determination of poly-morphic purity in both the drug substance and the drug product as well as the amorphous content in the drug substance assures product quality and reliability.…adapted to your substance…Crystallization DevelopmentProper solid-state characterization combined with a proven crystallization development pro-gram leads to robust, reproducible, and scalable crystallization processes that generate the de-sired crystalline form, size, and shape. …and development stage.Consulting and Patent SupportOur experts can provide evaluation of studies or individual data, along with comprehensive reports and testimonials. Our patent and search teams provide an effective resource for pro-tecting your valuable intellectual property and maintaining a competitive advantage.Solvias provides comprehensive physical chemistry services for the identification and selection of polymorphs, salts, and co-crystals, including method development for polymorphic purity and the optimization of crystallization processes. With years of drug development experience as a former research group of a major pharmaceutical company, we can help you crystallize your ideas.-3-Polymorphism, Salts & Crystallization An Integrated Approach to Solid-State DevelopmentPolymorphismScreeningSelection ofBest Form forDevelopmentCrystallizationOptimizationCrystallizationMonitoringQuality ControlKinetic Stability(DS/DP)Method forPolymorphPurity (DS/DP)Co-Crystal ScreeningSalt ScreeningCrystallizationScreeningPatentingFor the best overall results, Solvias provides an integrated and comprehensive approach to solid-state development – from systematic salt, co-crystal, and polymorph screening to controlled scale-up of the crystallization process, all complemented with the full range of physico-chemical studies performed in our laboratories.Polymorphism, Salts & CrystallizationSchematic and abbreviated diagram of the developmental phases of a drug with highlighted specific solid form tasks.Solvias specifically adapts its services to the developmental stage of your drug and provides you with the most valuable information precisely when you need it.Phase 1 Phase 2 Phase 3 Approval & MarketingPreclinical Phase From preclinical development through manufacture of the final drug product, the identification, selection, and understanding of the solid forms will have an enormous practical and commercial impact. At Solvias we follow specifically designed strategies to best fit the development process of drugs.Solid form considerations, screening and selectionFormulation Intellectual property for salts, co-crystals and polymorphsManufacturing process, crystallizationQuality controlProduct life cycle managementSpecific Solid-State Development Tasks General Solid-State Activities during Development - Salt and Co-Crystal Screening and Selection - Early Phase Polymorphism- Crystallization ScreeningLate Phase PolymorphismFinalCrystallization Process-4-Selection of the Best Solid Form -5-Screening• Salt and co-crystal screening • Crystallization screeningSelection• Physico-chemical parameters • Chemical stability • Solubility • HygroscopicityPolymorphism• Number of polymorphs • Hydrates• Polymorphic transformations• Complexity Solvias Salt and Co-Crystal Screening ProgramsSolvias Crystallization Screening ProgramsSolvias Characterization Programsfor Free Drug, Salts, and Co-Crystals• Physico-chemical parameters • Stability programs• Bulk propertiesSolvias Polymorphism Programs• Early phase• Late phase• HTSImportant Physical and Chemical Parameters for Selection of the Best Crystalline Solid Form• Stability (chemical and physical) • Solubility/dissolution• Hygroscopicity• Melting point• Polymorph landscape complexity and polymorphic transformations• Number of polymorphs• Processability• Ease of preparation-6-Free DrugCrystallineCandidates?Salt and/orCo-CrystalScreeningCandidates:• Free Drug• Co-CrystalsCandidates:• Free Drug• Salts• Co-CrystalspKa(s)?CharacterizationGoodSolid Forms?Select BestSolid FormCrystallizationScreeningno yesyesyesnonoServicesSolvias Solid-State Development Programs Designed to Meet Your NeedsSolid Form Screening and Selection• Polymorphs, salts, and co-crystals• Selection of the best solid form • High-throughput screening as well as conventional approach• Understanding of polymorphic transformations• Preformulation characterization • From mg to kg scale• Menu-style programs, tiered approach Crystallization• Crystallization screening to crystallize amorphous and difficult to crystallize compounds• Crystallization optimization to improve polymorphic purity, chemical purity, yield, rate, size, and morphology• Scale-up developmentMethod Development and Validation• Polymorphic purity• Amorphous content• Polymorphic form in drug product Support• Troubleshooting• Consulting• Patent support• Expert reports and testimonialsQuality Control • Drug substance• Drug product Quality Management• ISO-9001-certified QM system SQS• cGMP inspected and approved contract laboratory• GLP on request• Efficient integrated approach, proven study strategies• Flexibility: modular approach, with decision points throughout the programs• Large solid-state group with an outstanding track record• Generation of intellectual property for the customer• Ability to handle highly potent and cytotoxic compounds• Complete project management • State-of-the-art technology and hyphenated techniques to explore the polymorph landscape and understand the polymorphic transformationsFeatures & Key Success Factors-7-Solvias AGRömerpark 24303 KaiseraugstSwitzerland Tel. +41 61 845 60 00 Fax +41 61 845 69 00info@solvias.comwww.solvias.com 2.07.6e-8-