Vous êtes sur la page 1sur 18

Pharmacy and Biotechnology

Department of Pharmaceutical Technology

Pharmaceutics I
PHTC 311

Tutorial 5: Factors Affecting Solubility and Dissolution Rates

Course Instructors:
Prof. Dr. Samar Mansour
Dr. Salma Tammam
Dr. Mai Rady

Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 1


Factors Affecting Solubility and Dissolution Rates

Solubility Dissolution Rates

The extent to which the dissolution


proceeds under a given set of The amount of solutes dissolves by time
experimental conditions.

Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 2


How dissolution Occur?
Solids: The intermolecular cohesive
forces between solid materials are very
high, spaces between molecules are the
least and molecules only vibrate.

Solute Solvent Gases: The intermolecular cohesive


A molecule from the surface of the solute forces are the least, spaces between
is removed, reallocated into cavities of molecules are wide and molecules move
solvent.
freely in space.

Liquids: They are intermediate between


solids and gasses.
Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 3
Factors Affecting Solubility and Dissolution Rates

Dissolution
Solubility
Rate
Surface Area(A)
Temperature Solubility of the solute(CS)
Chemical Structure Diffusion Coefficient of Solute (D)
Polarity of the solvent The Solubility of Solute in the
Bulk(C)

Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 4


Factors Affecting Solubility

Temperature
Increasing temp. increases solubility
in endothermic processes

Chemical Polar solvents


Higher
structure (polar dissolves drugs with
groups -salts Solubility polar groups or salts

Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 5


Dissolution Rate
Dissolution rate: The rate of mass transfer to solution (dm/dt)
Noyes-Whitney Steps of dissolution:
Equation:
1. Molecules from the surface of the solid crystal
dissolve in the solvent surrounding the surface
of the crystal forming ‘’stagnant layer of
saturated solution’’.

Saturated solution 2. Diffusion of solute molecules to the bulk of


solution.

Cs D is the diffusion coefficient.


A is the surface area of the solid crystal.
Cs is the saturated concentration of solute in the
Bulk solution C stagnant layer.
C is concentration of solute in the bulk solution.
h is the thickness of the stagnant layer..

Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 6


Factors Affecting Dissolution Rate

1. Surface Area of Un-dissolved Solid:

Fast Porous Particles


Small Particles
Dissolution

Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 7


Factors Affecting Dissolution Rate

2. Saturated Solution (Cs):


Solutes with
hydrophilic groups
or salts

Polar Solvents Fast Polymorph of


dissolves solutes higher solubility
with Polar Groups Dissolution

Temperature No Common ion No Salting out


effect

Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 8


Factors Affecting Dissolution Rate
3. Concentration of Solute in The Bulk solution:

Increase volume Fast Removal of solute


of dissolution (Absorption)
medium Dissolution

Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 9


Factors Affecting Dissolution Rate

4. The diffusion Coefficient (D)


Diffusion coefficient is affected by:

Small MWt of
Solutes

Decrease Decrease viscosity


thickness of Fast of dissolution
stagnant layer (h) Dissolution medium
by agitation

Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 10


Approaches to Enhance Solubility of Drugs

Co-solvent (mix
Micronization water with less Add Hydrophilic groups or
polar solvents salt formation

Choose
amorphous drugs Solubility Solid dispersion
or polymorphs of increase
higher solubility

Adjust pH Solubilizing agents


Complex formation

Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 11


Questions
How to increase the dissolution of:
1. Chloramphinicol as an otic solution

2. Methyl Salycelate as an IM injection

3. Griseofulvin as Tablets to enhance its bioavailbility

Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 12


Problems
A solid is to be comminuted so as to increase its solubility by 30%. What must be the final particle size,
assuming that the surface tension of the solid is 200 dynes/cm and the volume per mole is 20 cm3? The
temperature is 25°C. R = 8.314 *107

Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 13


Factors Affecting Solubility
Practice Problems:

1. A solid is to be comminuted so as to increase its solubility by 30%. What must be the final particle
size, assuming that the surface tension of the solid is 200 dynes/cm and the volume per mole is 20
cm3? The temperature is 25°C. R = 8.314 *107

Answer:

S = ( 100% + 30%) = 130%

So = 100, Therefore log (S/S0) = 0.11

M/ ρ = V/mole = 20
T = 25 + 273 = 298ºC
= 1.27*10-6 cm = 1.27* 10-2 μm
Problems
1. Pentothal is a weak acid its pka is 7.4 determine the ratio between ionized and unionized
forms at pH 4.5 and 7.4 and determine the increase in solubility.
S = SI + Su , SI is solubility of ionized drug, Su = solubility of unionized drug. Su = 0.0398mg/ml

Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 15


Solubity Expressions
1. Quantity per quantity:
weight or volume of solute per weight or volume of solution
Ex: 1g/L, 1g/100ml

2. Percentage:
% w/v = (weight of solute/ volume of solution) x 100
% w/w = (weight of solute/ weight of solution) x 100
% v/v = (volume of solute/ volume of solution) x 100

Ex: 30%(w/v) = 30 grams of solute per 100ml of solution.

3. Parts:
Pharmacopoeias sometimes express concentrations in terms of number of solute
dissolved (parts) in a stated number of solvent (parts).

Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 16


Solubity Expressions
4. Molarity:
Is the number of moles of solute in 1 liter solution. Solutions of equal molarity contain the same number
of solute molecules in a given volume of solution. The unit of molarity is mol/L

5. Molality:
Is the number of moles of solute dissolved in 1000g of the solvent. According to the nature of the solute-
solvent interaction, the final volume may be greater than or less than 1000ml. In very dilute molal solution, the
volume may be 1000ml.
The unit of molality is mol/Kg

N.B: Molal solution does not depend on the temperature while molar
solution depends on the temperature.

6. Mole Fraction:
mole fraction of A = (moles of A)/(sum of moles of all components)

Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 17


Thank you
Pharmaceutical Technology Department - (PHTC 311) – Winter 2017 18