Presentation on theme: "PHM1213 Physical Pharmacy 1 2008/91 Introduction to Properties of Solids Kausar Ahmad Kausar Ahmad Kulliyyah of Pharmacy"— Presentation transcript:
PHM1213 Physical Pharmacy /91 Introduction to Properties of Solids Kausar Ahmad Kausar Ahmad Kulliyyah of Pharmacy
PHM1213 Physical Pharmacy /92 Contents General properties Intermolecular forces Types of solids Amorphous Crystalline Crystal structure Crystallisation Crystal growth
PHM1213 Physical Pharmacy /93 What is solid…..to pharmacy? Majority of drugs and excipients exist as solids Various dosage forms are prepared e.g. tablets, emulsions
PHM1213 Physical Pharmacy /94 General Properties Maintain shape Maintain shape Not fluid Not fluid Molecules/atoms/ions are held closely by Molecules/atoms/ions are held closely by intermolecular interatomic ionic forces
PHM1213 Physical Pharmacy /95 Intermolecular forces 1)Van der Waals forces a) a)Dipole-dipole (Keesom) b) b)Dipole-induced dipole (Debye) c) c)Induced dipole-induced dipole (London) 2)Ion dipole and ion-induced dipole forces 3)Hydrogen bonds
PHM1213 Physical Pharmacy /97 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 /911 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 TRICLINICMONOCLINICORTHOROMBIC TRIGONAL TETRAGONAL HEXAGONAL
PHM1213 Physical Pharmacy /912 Bravais Lattices End-centred i. i. Monoclinic ii. ii. orthorombic Face-centred i. i. Cubic (NaCl) ii. ii. Orthorombic Body-centred i. i. Cubic tetragonal ii. ii. Orthorombic Total of 14 possible types of unit cells For drugs, only 3 types: 1. Triclinic 2. Monoclinic 3. Orthorombic
PHM1213 Physical Pharmacy /913 FCC Structure of NaCl Small spheres represent Na + ions, large spheres represent Cl - ions. Each sodium ion is octahedrally surrounded by six chloride ions and vice versa.
PHM1213 Physical Pharmacy /915 Crystallisation Crystallisation steps from solution: Supersaturation of the solution e.g. cooling, evaporation, addition of precipitant or chemical reaction Formation of crystal nuclei e.g. collision of molecules, deliberate seeding Crystal growth around the nuclei
PHM1213 Physical Pharmacy /916 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 /917 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 /918 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. Handbook for Teachers of Chemistry Source: Shakhashiri, B.Z. Chemical Demonstrations: A Handbook for Teachers of Chemistry
PHM1213 Physical Pharmacy /919 End of lecture 1 of 2
PHM1213 Physical Pharmacy /920 Crystallisation
PHM1213 Physical Pharmacy /921 Contents - 2 Properties of solids and implications Crystal habits Crystal habits Types of crystal habit Types of crystal habit Factors affecting habits Factors affecting habits Polymorphism Polymorphism Methods to characterise solids
PHM1213 Physical Pharmacy /922 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 /923 Factors affecting types of habits Temperature Solvent 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
PHM1213 Physical Pharmacy /924 ACICULAR Long and needle-like, thinner than prismatic but thicker than fibrous. Natrolite crystals can be good examples of acicular crystals.prismaticfibrous 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. Fluorite forms crystals that are a good example of equant crystals.Fluorite
PHM1213 Physical Pharmacy /925 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. acicularIndicoliteelbaite 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
PHM1213 Physical Pharmacy /926 Sodium Chloride Class: HalidesHalides Uses: Major source of salt and as mineral specimens.
PHM1213 Physical Pharmacy /927 Exercise How many forms of Adipic acid crystals exist? Refer Florence & Attwood
PHM1213 Physical Pharmacy /928 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 /929 Example Polymorphism 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 /930 Polymorphs of spironolactone 1
PHM1213 Physical Pharmacy /931 Properties of Spironolactone Polymorphs ParametersForm 1Form 2 Unit cellorthorombic Dimension of a, b, c axes 0.998, 3.557, , 1.900, Crystal habitNeedle-likeprisms Melting point205 deg. C210 deg. C
PHM1213 Physical Pharmacy /932 Polymorphism in Pharmaceutical compounds drugspolymorphsamorphouspseudo ampicillin100 cortisone acetate 800 chlorampheni col palmitate 310 erythromycin200
PHM1213 Physical Pharmacy /933 Solubility of chloramphenicol palmitate Form B Form A 1: 1
PHM1213 Physical Pharmacy /934 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 /935 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 ( H f ) – heat required to melt (increase intermolecular distance) 1 g of solid Solubility
PHM1213 Physical Pharmacy /936 References AT Florence & D Attwood Physicochemical Principles of Pharmacy 3 rd. Ed, Macmillan (1998) Chapter 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 3 rd Ed., Prentice Hall, New Jersey (2001)