PHM1213 Physical Pharmacy 1 2008/91 Introduction to Properties of Solids Kausar Ahmad Kausar Ahmad...

PHM1213 Physical Pharmacy 1 2008/9PHM1213 Physical Pharmacy 1 2008/9 11

Introduction to Properties of Solids

Kausar AhmadKausar Ahmad

Kulliyyah of PharmacyKulliyyah of Pharmacy

http://staff.iiu.edu.my/akausarhttp://staff.iiu.edu.my/akausar


ContentsContents

General propertiesIntermolecular forces

Types of solidsAmorphousCrystalline

Crystal structure

CrystallisationCrystal growth


What is solid…..to pharmacy?

Majority of drugs and excipients exist as solids

Various dosage forms are preparede.g. tablets, emulsions


General PropertiesGeneral Properties

Maintain shapeMaintain shape

Not fluidNot fluid

Molecules/atoms/ions are held closely byMolecules/atoms/ions are held closely by

intermolecular

interatomic

ionic forces


Intermolecular forcesIntermolecular forces

1)1) Van der Waals forcesVan der Waals forces

a) Dipole-dipole (Keesom)

b) Dipole-induced dipole (Debye)

c) Induced dipole-induced dipole (London)

2)2) Ion dipole and ion-induced dipole forcesIon dipole and ion-induced dipole forces

3)3) Hydrogen bondsHydrogen bonds


Classification of SolidsClassification of Solids

AmorphousAmorphous

CrystallineCrystalline


Amorphous SolidsAmorphous 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


Crystalline SolidsCrystalline Solids

E.g. diamond, graphite

Regular shape i.e. fixed geometric patterns

Incompressible

Definite /specific boiling points

Diffract X-rays


Crystal StructureCrystal Structure

Crystals contain

highly ordered

molecules or atoms

held together by non-

covalent interactions

E.g. NaCl has the

cubic structure


Types of Crystal StructureTypes of Crystal Structure

1. Cubic

- sodium chloride

2. Tetragonal

- urea

3. Hexagonal

- iodoform

4. Rhombic

- iodine

5. Monoclinic

- sucrose

6. Triclinic

- boric acid

7. Trigonal


TRICLINIC MONOCLINIC ORTHOROMBIC

TRIGONAL TETRAGONAL HEXAGONAL


Bravais LatticesBravais Lattices

1. End-centred

i. Monoclinic

ii. orthorombic

2. Face-centred

i. Cubic (NaCl)

ii. Orthorombic

3. Body-centred

i. Cubic tetragonal

ii. Orthorombic

Total of 14 possible types of unit cells

For drugs, only 3 types:

1.1. TriclinicTriclinic

2.2. MonoclinicMonoclinic

3.3. OrthorombicOrthorombic


FCC Structure of NaClFCC 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.


Binding ForcesBinding Forces

Solid Type Binding force

NaCl cubic Electrostatic attraction

diamond tetragonal Covalent

graphite hexagonal Covalent

fatty acids ? Van der Waals & hydrogen bonding

metallic ? ?


CrystallisationCrystallisation

Crystallisation steps from solution:-

1. Supersaturation of the solutione.g. cooling, evaporation, addition of precipitant or chemical reaction

2. Formation of crystal nucleie.g. collision of molecules, deliberate seeding

3. Crystal growth around the nuclei


Crystal GrowthCrystal Growth

Steps involved:

1. Transport of molecules to the surface

2. Arrangement in the lattice

Degree of agitation in the system affects the diffusion coefficient, thus affects crystal growth.


PrecipitationPrecipitation

1. 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.


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 ChemistryHandbook for Teachers of Chemistry


End of lecture 1 of 2End of lecture 1 of 2


CrystallisationCrystallisation


Contents - 2Contents - 2

Properties of solids and implications

Crystal habitsCrystal habits

Types of crystal habitTypes of crystal habit

Factors affecting habitsFactors affecting habits

PolymorphismPolymorphism

Methods to characterise solids


Crystal HabitsCrystal Habits

Variation in sizeNumber of facesKind of facesHabits describe the overall shape of the

crystal e.g. acicular (needle), prismatic, pyramidal, tabular, equant, columnar & lamellar types.


Factors affecting types of habitsFactors 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 impuritiese.g.sulfonic acid dyes alter habits of ammonium, sodium and potassium nitrates

Presence of surfactantse.g. anionic & cationic surfactants on adipic acid crystals


ACICULARLong and needle-like, thinner than prismatic but thicker than fibrous. Natrolite crystals can be good examples of acicular crystals.

EQUANTAny 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.


PRISMATICOne 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.

TABULARBook-like (tablets) that are thicker than platy but not as elongated as bladed. Wulfenite forms crystals that are a good example of tabular crystals.


Sodium Chloride Class: Halides Uses: Major source of salt and as mineral specimens.


ExerciseExercise

How many forms of

Adipic acid crystals

exist?

Refer Florence & Attwood


PolymorphismsPolymorphisms

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.


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


Polymorphs of spironolactone

1


Properties of Spironolactone Polymorphs

Parameters Form 1 Form 2

Unit cell orthorombic 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


Polymorphism in Pharmaceutical compounds

drugsdrugs polymorphspolymorphs amorphousamorphous pseudopseudo

ampicillinampicillin 11 00 00

cortisone cortisone acetateacetate

88 00 00

chloramphenichloramphenicol palmitatecol palmitate

33 11 00

erythromycinerythromycin 22 00 00


Solubility of chloramphenicol palmitateSolubility of chloramphenicol palmitate

Form B

Form A

1: 1


Characterisation of Solids

1. 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


Continue characterisation of solids

4. 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 ( Hf) – heat required to melt

(increase intermolecular distance) 1 g of solid

8. Solubility


References

1. AT Florence & D AttwoodPhysicochemical Principles of Pharmacy 3rd. Ed, Macmillan (1998) Chapter 1

2. EA Rawlins, Bentley’s Textbook of Pharmaceutics

3. ME Aulton, Pharmaceutics: The Science of Dosage Form Design

4. JT Cartensen, Advance Pharmaceutical Solids, Marcel Dekker, New York (2001)

5. BD Cullity & SR Stock, Elements of x-ray diffraction 3rd Ed., Prentice Hall, New Jersey (2001)

PHM1213 Physical Pharmacy 1 2008/91 Introduction to Properties of Solids Kausar Ahmad Kausar Ahmad...

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