Introduction to Properties of Solids

1. Introduction to Properties of Solids Kausar Ahmad Kulliyyah of Pharmacy http://staff.iiu.edu.my/akausar PHM1213 Physical Pharmacy 1 2008/9

2. Contents • General properties • Intermolecular forces • Types of solids • Amorphous • Crystalline • Crystal structure • Crystallisation • Crystal growth PHM1213 Physical Pharmacy 1 2008/9

3. What is solid…..to pharmacy? • Majority of drugs and excipients exist as solids • Various dosage forms are preparede.g. tablets, emulsions PHM1213 Physical Pharmacy 1 2008/9

4. General Properties • Maintain shape • Not fluid • Molecules/atoms/ions are held closely by • intermolecular • interatomic • ionic forces PHM1213 Physical Pharmacy 1 2008/9

5. Intermolecular forces • Van der Waals forces • Dipole-dipole (Keesom) • Dipole-induced dipole (Debye) • Induced dipole-induced dipole (London) • Ion dipole and ion-induced dipole forces • Hydrogen bonds PHM1213 Physical Pharmacy 1 2008/9

6. Classification of Solids • Amorphous • Crystalline PHM1213 Physical Pharmacy 1 2008/9

7. Amorphous Solids • E.g. silica gel, synthetic plastics/polymers • Irregular shape - molecules are arranged in a random manner • No definite melting point- no crystal lattice to break • Exhibit characteristic glass transition temperature, Tg • Flow when subject to pressure over time • Isotropic i.e. same properties in all direction • Affect therapeutic activity e.g. amorphous antibiotic novobiocin is readily absorbed and therapeutically active compared to the crystalline form PHM1213 Physical Pharmacy 1 2008/9

8. Crystalline Solids • E.g. diamond, graphite • Regular shape i.e. fixed geometric patterns • Incompressible • Definite /specific boiling points • Diffract X-rays PHM1213 Physical Pharmacy 1 2008/9

9. Crystal Structure • Crystals contain highly ordered molecules or atoms held together by non-covalent interactions • E.g. NaCl has the cubic structure PHM1213 Physical Pharmacy 1 2008/9

10. Cubic- sodium chloride Tetragonal- urea Hexagonal - iodoform Rhombic- iodine Monoclinic- sucrose Triclinic- boric acid Trigonal Types of Crystal Structure PHM1213 Physical Pharmacy 1 2008/9

11. CrystalSites: CrystalHome StrukturberichtDesignation PearsonSymbol SpaceGroup PrototypeIndex FAQ References OtherSites NRLSites: NRLHome MSCT6000 MSTD6300 CCMS6390 Index by Space Group Space groups are listed in the order they appear in the Crystallographic Tables. Where it conflicts with the Crystallographic Tables we use the notation in Pearson's Handbook. Space Group generators, Wyckoff positions, etc., are available online via the very useful Bilbao Crystallographic Server, and at the National Research Council of Canada's Generation of standard and alternate settings of the 230 Space Groups page. The easiest way to find information about a given space group is to use the Table of Space Group Symbols. We also have more information on how space groups are presented here. Each class of space groups corresponds to certain Pearson Symbols. Clicking on the appropriate symbol will take you to that part of the Pearson Symbol Index, Space Group Classes: Go back to Crystal Lattice Structure page. TRICLINIC MONOCLINIC ORTHOROMBIC HEXAGONAL TETRAGONAL TRIGONAL PHM1213 Physical Pharmacy 1 2008/9 The appearance of external hyperlinks does not constitute endorsement by the United States Department of Defense, the United States Department of the Navy, and the Naval Research Laboratory of the linked web sites, or the information, products or serveices contained therein. For other than authorized activities such as military exchanges and Morale, Welfare, and Recreation (MWR) sites, the United States Department of Defense, the Department of the Navy, and the Naval Research Laboratory does not exercise any editorial control over the information you may find at these locations. Such links are provided consistent with the stated purpose of this DoD web site. Return to CCMS home page

12. End-centred Monoclinic orthorombic Face-centred Cubic (NaCl) Orthorombic Body-centred Cubic tetragonal Orthorombic Total of 14 possible types of unit cells For drugs, only 3 types: Triclinic Monoclinic Orthorombic Bravais Lattices PHM1213 Physical Pharmacy 1 2008/9

13. Small spheres represent Na+ ions,large spheres represent Cl- ions. Each sodium ion is octahedrally surrounded bysix chloride ions and vice versa. FCC Structure of NaCl PHM1213 Physical Pharmacy 1 2008/9

14. Binding Forces PHM1213 Physical Pharmacy 1 2008/9

15. Crystallisation Crystallisation steps from solution:- • Supersaturation of the solutione.g. cooling, evaporation, addition of precipitant or chemical reaction • Formation of crystal nucleie.g. collision of molecules, deliberate seeding • Crystal growth around the nuclei PHM1213 Physical Pharmacy 1 2008/9

16. Crystal Growth Steps involved: • Transport of molecules to the surface • Arrangement in the lattice • Degree of agitation in the system affects the diffusion coefficient, thus affects crystal growth. PHM1213 Physical Pharmacy 1 2008/9

17. Precipitation • Induced by altering pH of solution to reach saturation solubility. • By chemical reaction to produce precipitate from a homogeneous solution. • The rate of reaction is important in determining habit. PHM1213 Physical Pharmacy 1 2008/9

18. Crystallization from Supersaturated Solutions of Sodium Acetate end lecture here • Description: A supersaturated solution of sodium acetate is crystallized by pouring it onto a seed crystal, forming a stalagmite-like solid. Heat is radiated from the solid. • Source: Shakhashiri, B.Z. Chemical Demonstrations: A Handbook for Teachers of Chemistry PHM1213 Physical Pharmacy 1 2008/9

19. End of lecture 1 of 2 PHM1213 Physical Pharmacy 1 2008/9

20. Crystallisation PHM1213 Physical Pharmacy 1 2008/9

21. Contents - 2 • Properties of solids and implications • Crystal habits • Types of crystal habit • Factors affecting habits • Polymorphism • Methods to characterise solids PHM1213 Physical Pharmacy 1 2008/9

22. Crystal Habits • Variation in size • Number of faces • Kind of faces • Habits describe the overall shape of the crystal e.g. acicular (needle), prismatic, pyramidal, tabular, equant, columnar & lamellar types. PHM1213 Physical Pharmacy 1 2008/9

23. Factors affecting types of habits • Temperature • Solvent • Crystal growth ratee.g. at high rate, acicular form of phenylsalicylate is formed • Viscositye.g. less viscous media favours coarse and equidimensional forms of minerals • Addition of impuritiese.g.sulfonic acid dyes alter habits of ammonium, sodium and potassium nitrates • Presence of surfactantse.g. anionic & cationic surfactants on adipic acid crystals PHM1213 Physical Pharmacy 1 2008/9

24. EQUANT Any three perpendicular axis through the crystal are more or less equal. Can be used to describe rounded as well as angular crystals. Fluorite forms crystals that are a good example of equant crystals. ACICULAR Long and needle-like, thinner than prismatic but thicker than fibrous.Natrolite crystals can be good examples of acicular crystals. PHM1213 Physical Pharmacy 1 2008/9

25. PRISMATIC One of the most common of crystal habits. Prismatic crystals are "pencil-like", elongated crystals that are thicker than needles (see acicular). Indicolite (a variety of elbaite) forms good examples of prismatic crystals. TABULAR Book-like (tablets) that are thicker than platy but not as elongated as bladed.Wulfenite forms crystals that are a good example of tabular crystals. PHM1213 Physical Pharmacy 1 2008/9

26. Sodium Chloride Class: Halides Uses: Major source of salt and as mineral specimens. PHM1213 Physical Pharmacy 1 2008/9

27. Exercise How many forms of Adipic acid crystals exist? Refer Florence & Attwood PHM1213 Physical Pharmacy 1 2008/9

28. Polymorphisms • When compounds crystallise as different polymorphs, properties change. • Molecules arrange in two or more ways in the crystal: packed differently in crystal lattice, different orientation, different in conformation of molecules at lattice site. • X-ray diffraction patterns change. PHM1213 Physical Pharmacy 1 2008/9

29. ExamplePolymorphism of Spironolactone • A diuretic (no potassium loss) • 2 polymorphic forms and 4 solvated crystalline • Form 1: spironolactone powder is dissolved in acetone at a temperature near boiling point and cooled to 0 deg. C within a few hours – needle-like • Form 2: powder dissolved in acetone or dioxane or chloroform at RT and acetone allowed to evaporate for several weeks - prism PHM1213 Physical Pharmacy 1 2008/9

30. Polymorphs of spironolactone 1 PHM1213 Physical Pharmacy 1 2008/9

31. Properties of Spironolactone Polymorphs PHM1213 Physical Pharmacy 1 2008/9

32. Polymorphism in Pharmaceutical compounds PHM1213 Physical Pharmacy 1 2008/9

33. Solubility of chloramphenicol palmitate Form B 1: 1 Form A PHM1213 Physical Pharmacy 1 2008/9

34. Characterisation of Solids • Microscopy – polarised light • X-ray crystallography - single crystal- on the basis that crystals can diffract X-rays- wavelengths same magnitude as distance between atoms/molecules in crystal- enable the determination of the distances of various planes in crystals. Thus, structures.- e.g. penicillin • X-ray diffraction– powder sample >>polymorphic state PHM1213 Physical Pharmacy 1 2008/9

35. Continue characterisation of solids • Differential scanning calorimetry – Tg, Tc and Tm • Infrared spectrometry • Melting point – pure solid & liquid in equilibrium normal at 1 atm • Heat of fusion ( Hf) – heat required to melt (increase intermolecular distance) 1 g of solid • Solubility PHM1213 Physical Pharmacy 1 2008/9

36. References • AT Florence & D AttwoodPhysicochemical Principles of Pharmacy 3rd. Ed, Macmillan (1998) Chapter 1 • EA Rawlins, Bentley’s Textbook of Pharmaceutics • ME Aulton, Pharmaceutics: The Science of Dosage Form Design • JT Cartensen, Advance Pharmaceutical Solids, Marcel Dekker, New York (2001) • BD Cullity & SR Stock, Elements of x-ray diffraction 3rd Ed., Prentice Hall, New Jersey (2001) PHM1213 Physical Pharmacy 1 2008/9