LEC 3Solid state

by Dr Manal AL Soub

Process of Dissolution

DISSOLUTION MECHANISM• 1. Interfacial reaction that results in liberation of solute molecule from the solid phase, The solution in contact with solid will become saturated (Cs).• 2. The solute molecules migrate through the boundary layers surrounding the crystal to the bulk of solution, at which concentration is (C).• Boundary layer is nearly static and surround all wetted surface of the solid.• Mass transfer is slowly through the boundary layer to the bulk of solution.

DISSOLUTION MECHANISM• Interfacial reaction that results in liberation of

solute molecule from the solid phase, The solution in contact with solid will become saturated (Cs).

• The solute molecules migrate through the boundary layers surrounding the crystal to the bulk of solution, at which concentration is (C).

• Boundary layer is nearly static and surround all wetted surface of the solid.

• •Mass transfer is slowly through the boundary layer to the bulk of solution.

NOYES-WHITNEY EQUATION The rate of dissolution will depend on the slowest step, migration throughboundary layer Where K is the dissolution rate constant • k = DA/δ• Cs is the concentration of the solute at surface available for migration• D is the diffusion coefficient (m2/s)• A is the area available for molecular migration• δ is the thickness of the boundary layer

Mechanism of dissolution

Dissolution determines the cumulative amount of drug that goes into solution as a function of time

Steps involved liberation of the solute or drug from the formulation

matrix (disintegration) dissolution of the drug (solubilization of the drug

particles) in the liquid mediumThe overall rate of dissolution depends on the slower

of these two steps

RELATIONSSMALLER THE DRUG PARTICLE, GREATER THE

SURFACE AREA.

1.PARTICLE SIZE INVERSELY PROPOTIONAL TO : SURFACE AREA

ABSORPTION BIOAVALABILITY

2.PARTICLE SIZE IS DIRECTLY PROPORTIONAL TO: DOSE ADMINISTERED FLOW PROPERTY .

Reduction in Particle size improve solubility of drug.

Basically reduction in particle size increase contact surface area of the particle, there by ultimately it increase rate of solubility of drug.

Reduction Of Particle size

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Conclusion :

• Conclusion As the particle size and powder properties ultimately effects the drug release from the dosage form, importance should given to it while designing the dosage form for the good release of the drug and to avoid side effects. Particle size is an important parameter both for the production of medicines containing particulate solids and in the efficacy of the medicine administration.

Wetting of powdersThe wettability is Penetration of water into

tablets or into granules precedes dissolution. The wettability of the powders, as measured by the contact angle (θ) of the substance with water

contact angle

• The measurement of the contact angle gives an indication of the nature of the surface.

• The behaviour of crystalline materials can be related to the chemical structure of the materials

Wetting of powders• Hydrophobic drugs have dual

problems: they are not readily wetted, and even when wetted they have low solubility. On the other hand, because they are lipophilic , absorption across lipid membranes is facilitated.

The wetting of a solid when a liquid spreads over its surface is referred to as spreading wetting. The forces acting on a drop on the solid surface are represented by Young’s equation:

γS/A = γS/L + γL/A cos θ• where γS /A is the surface tension of the solid,• γS /L is the solid–liquid interfacial tension, • γL /A is the surface tension of the liquid and• θ is the contact angle.

• The tendency for wetting is expressed by the spreading coefficient S , as:

S = γL/A (cos θ – 1)

•For complete spreading of the liquid over the solid surface, S should have a zero or positive value. If the contact angle is larger than 0°, the term ( cos θ – 1) will be negative, as will the value of S.

spontaneous wetting is thus a zero value for the contact angle

Wettability and Dissolution Rate of powders

The first step in the process of dissolution is wetting of the dissolving surface ,which is in contact with the dissolution medium.

The condition for complete wetting of a solid surface is that the contact angle should be Zero.

This condition is fulfilled only when the forces of attraction between the liquid and solid are equal to or greater than those between liquid and liquid.

Solid – Dispersion System

• Definition :

Solid dispersion is defined as dispersion of one or more active ingredients in an inert carrier or matrix at solid state prepared by the melting, solvent or melting solvent method.

Classification(Based on Fast Release Mechanism) • Simple Eutectic Mixtures

• Solid Solutions

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A. Eutectic Mixtures• When two or more substances are

mixed together they liquefy due to the lowering of melting point than their individual melting point. Such substances are called as eutectic substances.

e.g. paracetamol-urea, griseofulvin-urea

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Phase diagram (temperature versus composition) showing boundaries between liquid and solid

phases, andthe eutectic point, E.

• The following factors may contribute to faster dissolution rate of drug dispersed in the eutectic mixtures:-1. Increase in drug solubility.2. Solubilization effect by the carrier which completely dissolves in a short time in diffusion layer surrounding drug particles.3. Absence of aggregation and agglomeration between fine crystallites of pure hydrophobic drug. 21

A. Eutectic Mixtures

4. Excellent wettability and dispersibility of a drug as the encircling soluble carrier readily dissolves and causes water to contact as wet drug particles.

5. Crystallization of drug in a metastable form after solidification from fused solution, which has high solubility.

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A. Eutectic Mixtures

• Eutectics are easy to prepare and economical with no solvents involved. The method however cannot be applied to: - Drugs which fail to crystallize from

mixed melt. - Thermolabile drugs. - Carriers such as succinic acid that decompose at melting point. 23

A. Eutectic Mixtures

B. Solid Solutions• It is made up of a solid solute dissolved in a solid

solvent. It is often called a “mixed crystal” because the two components crystallize together in a homogenous phase system.

• It is prepared by fusion method.

• A solid solution of poorly soluble drug in a rapidly soluble carrier achieves a faster dissolution because particle size of drug is reduced to molecular size.

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