1. PHM1153 Physical Pharmacy 1 2010/11 Kausar Ahmad Kulliyyah of Pharmacy
Solids
Kausar Ahmad
Kulliyyah of Pharmacy
PHM1153 Physical Pharmacy /12

2. Contents General properties Types of solids Amorphous Crystalline
Crystal structure
Crystallisation
Crystal growth
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3. What is solid…..to pharmacy?
Majority of drugs and excipients exist as solids
Various dosage forms are prepared e.g. tablets, emulsions
Types of solids affect
Processing
Efficacy
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4. General Properties Maintain shape Not fluid
Molecules/atoms/ions are held closely by
intermolecular
interatomic
ionic forces
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5. Intermolecular forces
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Intermolecular forces
Van der Waals forces
Dipole-dipole (Keesom) e.g. HCl
Dipole-induced dipole (Debye)
Induced dipole-induced dipole (London)
Ion dipole and ion-induced dipole forces
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.
Exercise
Describe in your own words the action of each force above and give examples.
Arrange the forces in decreasing strength.
Dipole-Induced Dipole Forces
A dipole-induced dipole attraction is a weak attraction that results when a polar molecule induces a dipole in an atom or in a nonpolar molecule by disturbing the arrangement of electrons in the nonpolar species.
Ion-Induced Dipole Forces
An ion-induced dipole attraction is a weak attraction that results when the approach of an ion induces a dipole in an atom or in a nonpolar molecule by disturbing the arrangement of electrons in the nonpolar species.
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6. Classification of Solids
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Classification of Solids
Amorphous
Crystalline
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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
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8. Crystalline Solids E.g. diamond, graphite
Regular shape i.e. fixed geometric patterns
Incompressible
Definite /specific boiling points
Diffract X-rays
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9. PHM1153 Physical Pharmacy 1 2010/11
Crystal Structure
Crystals contain highly ordered molecules or atoms held together by non-covalent interactions
E.g. NaCl has the cubic structure
But the cubic structure in 3D can be further classified into symmetrical lattices i.e. it may be face centred, body centred or simply a primitive cube. What is meant by a primitive cube? This is basically the most simple form of a cube.
During crystal growth, depending on the crystallisation conditions, the Na+ and Cl- ions may arrange themselves in a different manner. Why?
Let’s say the crystallisation takes place at a high temperature. We would expect that the ions would have far greater kinetic energy compared to crystallisation that takes place at lower temperature.
In this instance, there would be a higher possibility for the ions to arrange themselves in the lattice in a way that would not obstruct their movement that much. Hence, the primitive cubic structure is dominant.
If the crystallisation temperature is very low, the ions would be able to arrange themselves neatly in the cubic structure, in a more dense fashion , which would give the face centred cubic structure.
You will appreciate this more when you do the experiment on the polymorphism of L-glutamic acid in Dosage Design 1.
Source:
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10. PHM1153 Physical Pharmacy 1 2010/11
           
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:  1 Jan 1998
Last Modified: 18 Jan 2003
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:
Class
Pearson Symbols
                 
Triclinic Structures (#1-#2)
aPn
Monoclinic Structures (#3-#15)
   mPn    mCn   
                
Orthorhombic Structures (#16-#74)
   oPn    oFn    oIn    oCn   
Tetragonal Structures (#75-#142)
   tPn    tIn   
Trigonal Structures (#143-#167)
   hPn    hRn
                  
Hexagonal Structures (#168-#194)
   hPn   
Cubic Structures (#195-#230)
   cPn    cFn    cIn   
Go back to Crystal Lattice Structure page.
Structures indexed by:
Strukturbericht Designation
Pearson Symbol
Prototype
Current URL: lattice/spcgrp/index.html This page was created at the Naval Research Laboratory Center for Computational Materials Science Send comments and corrections to (Privacy Advisory)
PHM1153 Physical Pharmacy /11
TRICLINIC
boric acid
ORTHOROMBIC
iodine
MONOCLINIC
sucrose
In some texts, the crystal structure consists of only six types. The reason is, the trigonal is considered as a part/subset of the hexagonal.
The crystal structure is considered a point group. Once the atom, ions or molecules arranged themselves in the lattice, the trigonal structure transforms to a rhombohedral lattice.
TRIGONAL ?
TETRAGONAL
urea
HEXAGONAL
iodoform
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11. PHM1153 Physical Pharmacy 1 2010/11
Crystal Lattices in 3D
Crystal lattice
End centred
Side centred
Face centred
Body centred
Bravais/ Total
Cubic 1 3
Triclinic
Monoclinic 2
Orthorhombic 4
Hexagonal
Rhombohedral
Tetragonal
Total unit cells 7 14
Bravais lattices is a set of space lattices in 3D.
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12. PHM1153 Physical Pharmacy 1 2010/11
Lattices for drugs
For drugs, only 3 types:
Triclinic
Monoclinic
Orthorombic
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13. 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.
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14. PHM1153 Physical Pharmacy 1 2010/11
Binding Forces
Solid
Crystal structure
Binding force
NaCl
cubic
Electrostatic attraction
Diamond ?
Covalent
Graphite
hexagonal
Fatty acids
Van der Waals & hydrogen bonding
Gold
Mefenamic acid
Salicylic acid
Most organic compounds
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15. 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
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16. Crystal Growth Steps involved: 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
Arrangement in the lattice
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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.
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18. Crystallization 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
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19. End of lecture 1 of 2
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20. Crystallisation
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21. Contents - 2 Properties of solids and implications Crystal habits
Types of crystal habit
Factors affecting habits
Polymorphism
Methods to characterise solids
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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.
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23. Factors affecting types of habits
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
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24. Types of Habits EQUANT ACICULAR PRISMATIC TABULAR
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
ACICULAR
Long and needle-like, thinner than prismatic but thicker than fibrous. e.g. Natrolite
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.
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25. Sodium Chloride
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26. Exercise How many forms of adipic acid crystals exist?
Refer Florence & Attwood
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27. 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.
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28. 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
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29. Polymorphs of Spironolactone1
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30. Properties of Spironolactone Polymorphs
Parameters
Form 1
Form 2
Unit cell
Orthorombic
Dimension of
a, b, c axes
0.998, 3.557, 0.623
1.058, 1.900, 1.101
Crystal habit
Needle-like
Prisms
Melting point
205 deg. C
210 deg. C
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31. Polymorphism in Pharmaceutical Compounds
Drugs
Crystalline
Amorphous
Ampicillin 1
Cortisone acetate 8
Chloramphenicol palmitate 3
Erythromycin 2
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32. Solubility of Chloramphenicol Palmitate
Form B
Form B
1: 1
Form A
Form A
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33. 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
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34. 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
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35. References
Atkins, P & de Paula, J. (2002). Atkins’ Physical Chemistry 7th 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 3rd Ed. New Jersey: Prentice Hall. Florence, A. T. & Attwood, D. (1998). Physicochemical Principles of Pharmacy 3rd. Ed. London: Macmillan. Martin, A. (1993). Physical Pharmacy 4th Ed. Baltimore: Lippincott. Note: The 6th edition is now available. Smart, L. E. & Moore, E. A. (2005). Solid State Chemistry 3rd Ed. Boca Raton: CRC West, A. R. (1999). Basic Solid State Chemistry 2nd Ed. West Sussex: Wiley
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