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KAUSAR AHMAD KULLIYYAH OF PHARMACY PHM1153 Physical Pharmacy 1 2011/12 1 Solids

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Presentation on theme: "KAUSAR AHMAD KULLIYYAH OF PHARMACY PHM1153 Physical Pharmacy 1 2011/12 1 Solids"— Presentation transcript:

1 KAUSAR AHMAD KULLIYYAH OF PHARMACY PHM1153 Physical Pharmacy /12 1 Solids

2 Contents PHM1153 Physical Pharmacy /12 2 General properties Types of solids Amorphous Crystalline Crystal structure Crystallisation Crystal growth

3 What is solid… pharmacy? PHM1153 Physical Pharmacy /12 3 Majority of drugs and excipients exist as solids Various dosage forms are prepared e.g. tablets, emulsions Types of solids affect Processing Efficacy

4 General Properties PHM1153 Physical Pharmacy /12 4 Maintain shape Not fluid Molecules/atoms/ions are held closely by intermolecular interatomic ionic forces

5 Intermolecular forces PHM1153 Physical Pharmacy / Van der Waals forces i.Dipole-dipole (Keesom) e.g. HCl ii.Dipole-induced dipole (Debye) iii.Induced dipole-induced dipole (London) 2.Ion dipole and ion-induced dipole forces 3.Hydrogen bonds e.g. H2O In solids, average kinetic energy << strength of intermolecular forces Hence, each molecule can only move short distances around a fixed position.

6 Classification of Solids PHM1153 Physical Pharmacy /12 6 Amorphous Crystalline

7 Amorphous Solids PHM1153 Physical Pharmacy /12 7 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

8 Crystalline Solids PHM1153 Physical Pharmacy /12 8 E.g. diamond, graphite Regular shape i.e. fixed geometric patterns Incompressible Definite /specific boiling points Diffract X-rays

9 Crystal Structure Crystals contain highly ordered molecules or atoms held together by non- covalent interactions E.g. NaCl has the cubic structure PHM1153 Physical Pharmacy /12 9 Source:

10 PHM1153 Physical Pharmacy /12 10 Crystal Sites: Crystal Home Strukturbericht Designation Pearson Symbol Space Group Prototype Index FAQ References Other Sites NRL Sites: NRL Home MSCT 6000 MSTD 6300 CCMS 6390 Crystal Lattice Structures: Reference Date:Reference Date: 1 Jan 1998 Last Modified:Last Modified: 18 Jan 2003 Index by Space Group Space groups are listed in the order they appear in the Crystallographic Tables. Crystallographic Tables Where it conflicts with the Crystallographic Tables we use the notation in Pearson's Handbook.Crystallographic TablesPearson's Handbook Space GroupSpace 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.Wyckoff positionsBilbao Crystallographic ServerGeneration of standard and alternate settings of the 230 Space GroupsTable of Space Group Symbols We also have more information on how space groups are presented here.more information 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,Pearson Symbols Space Group Classes: ClassPearson Symbols Triclinic Structures (#1-#2) aPn Monoclinic Structures (#3-#15) mPn mCn mPnmCn Orthorhombic Structures (#16-#74) oPn oFn oIn oCn oPnoFnoInoCn Tetragonal Structures (#75-#142) tPn tIn tPntIn Trigonal Structures (#143-#167) hPn hRnhPnhRn Hexagonal Structures (#168-#194) hPn Cubic Structures (#195-#230) cPn cFn cIn cPncFncIn Go back to Crystal Lattice Structure page. S t r u c t u r e s i n d e x e d b y : S t r u k t u r b e r i c h t D e s i g n a t i o n S t r u k t u r b e r i c h t D e s i g n a t i o n P e a r s o n S y m b o l P e a r s o n S y m b o l P r o t o t y p e P r o t o t y p e Current URL: page was created at theNaval Research LaboratoryCenter for Computational Materials ScienceSend comments and corrections to (Privacy Advisory) Current URL: page was created at theNaval Research LaboratoryCenter for Computational Materials ScienceSend comments and corrections to (Privacy Advisory) 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 TRICLINIC boric acid MONOCLINIC sucrose ORTHOROMBIC iodine TRIGONAL ? TETRAGONAL urea HEXAGONAL iodoform

11 Crystal Lattices in 3D Crystal latticeEnd centred Side centred Face centred Body centred Bravais/ Total Cubic1113 Triclinic11 Monoclinic112 Orthorhombic11114 Hexagonal11 Rhombohedral11 Tetragonal112 Total unit cells714 PHM1153 Physical Pharmacy /12 11

12 Lattices for drugs For drugs, only 3 types: 1. Triclinic 2. Monoclinic 3. Orthorombic PHM1153 Physical Pharmacy /12 12

13 FCC Structure of NaCl PHM1153 Physical Pharmacy /12 13 Small spheres represent Na + ions, large spheres represent Cl - ions. Each sodium ion is octahedrally surrounded by six chloride ions and vice versa.

14 Binding Forces PHM1153 Physical Pharmacy /12 14 SolidCrystal structure Binding force NaClcubicElectrostatic attraction Diamond?Covalent GraphitehexagonalCovalent Fatty acids?Van der Waals & hydrogen bonding Gold?? Mefenamic acid?? Salicylic acid??

15 Crystallisation PHM1153 Physical Pharmacy /12 15 Crystallisation steps from solution:- 1. Supersaturation of the solution e.g. cooling, evaporation, addition of precipitant or chemical reaction 2. Formation of crystal nuclei e.g. collision of molecules, deliberate seeding 3. Crystal growth around the nuclei

16 Crystal Growth PHM1153 Physical Pharmacy /12 16 Steps involved: 1. Transport of molecules to the surface Degree of agitation in the system affects the diffusion coefficient, thus affects crystal growth. Affinity of solute to solvent 2. Arrangement in the lattice

17 Precipitation PHM1153 Physical Pharmacy / Induced by altering pH of solution to reach saturation solubility. 2. By chemical reaction to produce precipitate from a homogeneous solution. The rate of reaction is important in determining habit.

18 Crystallization of Sodium Acetate end lecture here PHM1153 Physical Pharmacy /12 18 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

19 PHM1153 Physical Pharmacy /12 19 End of lecture 1 of 2

20 Crystallisation PHM1153 Physical Pharmacy /12 20

21 Contents - 2 PHM1153 Physical Pharmacy /12 21 Properties of solids and implications Crystal habits Types of crystal habit Factors affecting habits Polymorphism Methods to characterise solids

22 Crystal Habits PHM1153 Physical Pharmacy /12 22 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.

23 Factors affecting types of habits PHM1153 Physical Pharmacy /12 23 Temperature Solvent/s Crystal growth rate e.g. at high rate, acicular form of phenylsalicylate is formed Viscosity e.g. less viscous media favours coarse and equidimensional forms of minerals Addition of impurities e.g.sulfonic acid dyes alter habits of ammonium, sodium and potassium nitrates Presence of surfactants e.g. anionic & cationic surfactants on adipic acid crystals

24 Types of Habits PHM1153 Physical Pharmacy /12 24 ACICULAR Long and needle- like, thinner than prismatic but thicker than fibrous. e.g. Natrolite prismatic fibrous Natrolite EQUANT Any three perpendicular axis through the crystal are more or less equal. Can be used to describe rounded as well as angular crystals. e.g. Fluorite Fluorite PRISMATIC Common crystal habit. Prismatic crystals are "pencil-like", elongated crystals that are thicker than needles. 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. platybladed Wulfenite

25 Sodium Chloride PHM1153 Physical Pharmacy /12 25

26 Exercise PHM1153 Physical Pharmacy /12 26 How many forms of adipic acid crystals exist? Refer Florence & Attwood

27 Polymorphisms PHM1153 Physical Pharmacy /12 27 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.

28 Example: Polymorphism of Spironolactone PHM1153 Physical Pharmacy /12 28 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

29 Polymorphs of Spironolactone PHM1153 Physical Pharmacy /

30 Properties of Spironolactone Polymorphs PHM1153 Physical Pharmacy /12 30

31 Polymorphism in Pharmaceutical Compounds DrugsCrystallineAmorphous Ampicillin10 Cortisone acetate80 Chloramphenicol palmitate31 Erythromycin20 PHM1153 Physical Pharmacy /12 31

32 Solubility of Chloramphenicol Palmitate PHM1153 Physical Pharmacy /12 32 Form B Form A 1: 1 Form B Form A

33 Characterisation of Solids PHM1153 Physical Pharmacy / Microscopy – polarised light 2. 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 3. X-ray diffraction – powder sample >>polymorphic state

34 Continue characterisation of solids PHM1153 Physical Pharmacy / Differential scanning calorimetry – Tg, Tc and Tm 5. Infrared spectrometry 6. Melting point – pure solid & liquid in equilibrium normal at 1 atm 7. Heat of fusion ( H f ) – heat required to melt (increase intermolecular distance) 1 g of solid 8. Solubility

35 References PHM1153 Physical Pharmacy /12 35 Atkins, P & de Paula, J. (2002). Atkins Physical Chemistry 7 th Ed. New York: Oxford. Cartensen, J. T. (2001). Advance Pharmaceutical Solids. New York: Marcel Dekker. Cullity, B. D. & Stock, S. R. (2001). Elements of x-ray diffraction 3 rd Ed. New Jersey: Prentice Hall. Florence, A. T. & Attwood, D. (1998). Physicochemical Principles of Pharmacy 3 rd. Ed. London: Macmillan. Martin, A. (1993). Physical Pharmacy 4 th Ed. Baltimore: Lippincott. Note: The 6 th edition is now available. Smart, L. E. & Moore, E. A. (2005). Solid State Chemistry 3 rd Ed. Boca Raton: CRC West, A. R. (1999). Basic Solid State Chemistry 2 nd Ed. West Sussex: Wiley

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