Physical Pharmacy Solubility Khalid T Maaroof MSc. Pharmaceutical sciences School of pharmacy Pharmaceutics department 1
Definition Solubility is the maximum amount of a solid, liquid or a gas solute that can be dissolved in a certain amount of solvent under specific conditions. The concentration of solute in a saturated solution The term (miscibility) is used when both the solute and the solvent are liquids. What is the difference between Solubility and Dissolution? 2
Definition A saturated solution: is one in which an equilibrium is established between dissolved and undissolved solute at a definite temperature. (No more solute can dissolve in the solvent) 3
Quantification Solubility is expressed in units of concentration such as: molality, molarity, mass concentration and percentage. The United States Pharmacopeia (USP) describes the solubility of drugs as parts of solvent required for one part solute. Very soluble Less than 1 Freely soluble 1-10 Soluble 10-30 Sparingly soluble 30-100 Slightly soluble 100-1000 Very slightly soluble 1000 10 000 Parts of solvent required to dissolve one part of solute Practically insoluble or insoluble Greater than or equal to 10 000 4
Nature of solute and solvent Polarity is a major factor in water solubility of chemicals and drugs. Polar solvents: e.g(water, glycols, methyl & ethyl alcohol), dissolve ionic solutes & other polar substances. Nonpolar compounds, can dissolve nonpolar solutes through induced dipole interactions The solute molecules are kept in solution by the weak van der Waals London type of forces 5
Nature of solute and solvent Semipolar solvents, such as ketones can induce a certain degree of polarity in non polar solvent molecules. They can act as intermediate solvents to bring about miscibility of polar & non polar liquids. Example: acetone increases solubility of ether in water Why Tertiary butyl alcohol is more soluble than n-butyl alcohol 6
Effect of temperature on solubility Generally, an increase in the temperature of the solution increases the solubility of a solid solute. For example, a greater amount of sugar will dissolve in warm water than in cold water. A few solid solutes, however, are less soluble in warmer solutions. When?? For all gases, solubility decreases as the temperature of the solution rises. An example of this is Soda. The solubility of the carbon dioxide gas decreases when a soda is warm, making the soda flat. 7
Effect of Pressure on solubility The effects of pressure are only significant in affecting the solubility of gases in liquids Henry s law: C=kp the concentration (C) of dissolved gas is proportional to the partial pressure (p) of the gas above the solution. (the partial pressure = total pressure above the solution minus the vapor pressure of the solvent) 8
Effect of Pressure on solubility
Effect of ph on solubility Acids are more soluble in basic solvents, and basic compounds are more soluble in acidic media. Phenol is weakly acidic and only slightly soluble in water but is quite soluble in dilute sodium hydroxide solution. An acidic drug is more soluble in stomach or small intestine? If the ph of a solution is increased what happens to the acidic solute in the solution? 10
Effect of ph on solubility Changes in solubility brought about by alterations of solvent ph can be predicted by the php equation. The php is the ph below which an acid or above which a base will begin to precipitate. where, 11
e.g. Calculate the php of a 1% sodium phenobarbital solution. (i.e. 1% phenobarbital will precipitate at or below a ph of 8.3)
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