1- States of matter & phase equilibria - part 1 (Physical Pharmacy)

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Khalid T MaaroofMSc. Pharmaceutical sciences

School of pharmacy – Pharmaceutics department

Online access: bit.ly/physicalpharmacy

States of matter

Physical Pharmacy

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This lectureBonds

IntermolecularVan der vals and dipole bonds

Ionic bonds & Ion dipole bonds

Hydrogen bonds

Intramolecular

States of matterSolids

Crystalline solidsPolymorphs

SolvatesMelting point and heat of

fusionAmorphous solids

Liquids

GasesIdeal gas law

Liquefaction of gases

Aerosols

Other states of interest

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Bonding forces

Intermolecular forces

Intramolecular forces

Repulsive forces

Attractive forces

In order for molecules to exist in aggregates in gases, liquids, and solids, intermolecular forces must exist.

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Inte

rmol

ecul

ar fo

rces

Van derWaals Forces

H- Bonding

Ion-Ion interactions

Ion-dipole interactions

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Dipole

• A polar molecule that has two poles.

Van derWaals Forces

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Van der Waals Forces

• nonionic interactions between molecules, yet they involve charge–charge interactions

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Hydrogen bond or hydrogen bridge

• Because of the small size of a hydrogen atom and its large field, it can move in close to the electronegative atom (fluorine, oxygen, or nitrogen) and form an electrostatic connection.

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Ion–Ion InteractionsStrong forces between counter ions.

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Ion-dipole and ion-induced dipole forces

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Questions !

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States of matter• Gases, liquids, and crystalline solids are the

three primary states of matter.

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Solids

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Melting point of crystalline solids

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The temperature at which a liquid passes into the solid state is known as the freezing point. It is also the melting point of a pure crystalline compound.

Normal freezing or melting point (at 1 atm)

heat of fusion: the heat required to increase the interatomic or intermolecular distances in crystals, thus allowing melting.

How intermolecular forces affect heat of fusion???

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Crystalline solids

• The units that constitute the crystal structure can be atoms, molecules, or ions. The sodium chloride crystal, consists of a cubic lattice of sodium ions interpenetrated by a lattice of chloride ions, the binding force of the crystal being the electrostatic attraction of the oppositely charged ions.

• In diamond and graphite, the lattice units consist of atoms held together by covalent bonds.

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• In organic compounds, the molecules are held together by van der Waals forces and hydrogen bonding, which account for the weak binding and for the low melting points of these crystals.

• ionic and atomic crystals in general are hard and brittle and have high melting points

• molecular crystals are soft and have relatively low melting points.

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Molecular weight, type of intermolecular bonds and molecular configuration, all can affect melting and freezing point of compounds.

In the picture below even number chains have higher melting points compared to odd number chains (No, of carbons) Why???

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Polymorphism• When a substance exists in more than one crystalline form, the

different form are designated as polymorphs and the phenomenon as polymorphism.

• Polymorphs have different stabilities and may spontaneously convert from the metastable form at a temperature to the stable form.

• carbon: diamond in a cubic (tetrahedral lattice arrangement )

• Graphite in sheet of a hexagonal lattice

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Depending upon their relative stability, one of the several polymorphic form will be physically more stable than others.

Stable polymorph represents the lowest energy state, has highest melting point and least aqueous solubility.

Metastable form represent the higher energy state, have lower melting point and high aqueous solubility .

Metastable form converts to the stable form due to their higher energy state.

Metastable form shows better bioavailability and therefore preferred in formulations.

Only 10% of the pharmaceuticals are present in their metastable form.

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Amorphous Solids They differ from crystalline solids in that they tend to

flow when subjected to sufficient pressure over a period of time, and they do not have definite melting points.

Whether a drug is amorphous or crystalline has been shown to affect its therapeutic activity.

the crystalline form of the antibiotic novobiocin acid is poorly absorbed and has no activity, whereas the amorphous form is readily absorbed and therapeutically active.

This is due to the differences in the rate of dissolution

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The Liquid state

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Boiling

If a liquid is placed in an open container and heated until the vapor pressure equals the atmospheric pressure, the vapor will form bubbles that rise rapidly through the liquid and escape into the gaseous state. The temperature at which

the vapor pressure of the liquid equals the external or atmospheric pressure is known as the boiling point.

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The boiling point may be considered the temperature at which thermal agitation can overcome the attractive forces between the molecules of a liquid. Therefore, the boiling point of a compound, like the heat of vaporization and the vapor pressure at a definite temperature, provides a rough indication of the magnitude of the attractive forces.

The boiling points of normal hydrocarbons, simple alcohols, and carboxylic acids increase with molecular weight. WHY??

Polar molecules usually have higher boiling point than nonpolar. WHY??

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Heat of Vaporization & critical temperature

• Clausius–Clapeyron Equation:

where p1 and p2 are the vapor pressures at absolute temperatures T1 and T2, and ∆Hv is the molar heat of vaporization, that is, the heat absorbed by 1 mole of liquid when it passes into the vapor state.

Heats of vaporization vary somewhat with temperature. For example, the heat of vaporization of water is 539 cal/g at 100◦C; it is 478 cal/g at 180◦C,

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Gases

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• Ideal Gases

• Real Gases

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Ideal gas law

Molar gas constant:

= 0.08205 liter atm/mole K= 8.314 × 106 erg/mole K = 1.987 cal/mole deg

For calculations related to this slide refer to the book

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Molecular weight Molecular weight can be determined using

ideal gas law:

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The van derWaals Equation for Real Gases

internal pressure per moleresulting from the intermolecular forces of attraction betweenthe molecules

incompressibility of themolecules, that is, the excluded volume, which is about fourtimes the molecular volume

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When the volume of a gas is large, the molecules are well dispersed. Under these conditions, a/V2 and b become insignificant with respect to P and V, respectively. Under these conditions, the van der Waals equation for 1 mole of gas reduces to the ideal gas equation, PV = RT, and at low pressures, real gases behave in an ideal manner.

Refer to the book example 2-5 chapter 2

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Liquefaction of Gases When a gas is cooled, it loses some of its kinetic energy

in the form of heat, and the velocity of the molecules decreases.

critical temperature: Above which it is impossible to liquefy a gas irrespective of the pressure applied

critical pressure: The pressure required to liquefy a gas at its critical temperature which is also the highest vapor pressure that the liquid can have.

The further a gas is cooled below its critical temperature, the less pressure is required to liquefy it.

The critical temperature of water is 374◦C, or 647 K. and its critical pressure is 218 atm,

At critical temperature ∆Hv of water = ???32 10/31/2015

Aerosols Advantages of aerosols. [refer to the book] Gases can be liquefied under high pressures in a closed

chamber as long as the chamber is maintained below the critical temperature.

When the pressure is reduced, the molecules expand and the liquid reverts to a gas.

Propellant: material that is liquid under the pressure conditions existing inside the container but that forms a gas under normal atmospheric conditions.

If the drug is nonvolatile, it forms a fine spray as it leaves the valve orifice; at the same time, the liquid propellant vaporizes off.

Chlorofluorocarbons and hydrofluorocarbons nitrogen and carbon dioxide. Metered dose inhalation products???

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Other Phases of matter

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The liquid crystalline state: Liquid Solid

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Supercritical fluid state: Liquid Gas

Critical temperature and pressure?

High density close to liquids, and low viscosity close to gases A gas that may have little to no ability to

dissolve a compound under ambient conditions can completely dissolve the compound under high pressure in the supercritical range.

They are used for: extraction, crystallization, and preparation of formulations

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Advantages of supercritical fluids when used as solvents

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the potential for low temperature extractions selectivity of the extracted compounds lower energy requirement and lower viscosity

than solvents. reduced toxicity and need for hazardous solvents

that require expensive disposal

An example is supercritical CO2, and the process of decaffeination of coffee.

Refer to the book p37

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Questions !

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