Solubility of Solids in Liquids PDF

# **Solubility of Solids in Liquids (Cont.)** - By - Prof. Mokhtar M. El-Baseir ## **pH and solubility** In order to ensure a clear homogenous solution and maximum therapeutic effectiveness, the preparations should be adjusted to an optimum pH. The relationship between the solubility of drugs and t...

# **Solubility of Solids in Liquids (Cont.)** - By - Prof. Mokhtar M. El-Baseir ## **pH and solubility** In order to ensure a clear homogenous solution and maximum therapeutic effectiveness, the preparations should be adjusted to an optimum pH. The relationship between the solubility of drugs and the pH is expressed by the following equations * **a- For acidic drug:** $pH=pk+log\frac{S-S_o}{S_o}$. Where S is the overall solubility of drug and $S_o$ is the solubility of unionized form. pKa is the partition coefficient. $S = S_o$ + solubility of ionized form. If the pH of the solution is known, then solubility of acidic drug at that pH can be calculated. * **b- For basic drug:** $pH=pK-pk+log\frac{S_o}{S-S_o}$ ## **Influence of solvents** Frequently a solute is more soluble in a mixture of solvents than in one solvent alone. This phenomenon is known as Cosolvency and the solvents known as Cosolvents. ### **Example** 1 g of Phenobarbital is soluble in 1000 ml of water, in10 ml of alcohol, in 40 ml chloroform and in 15 ml Ether. The solubility of Phenobarbital increased to 1.5% w/v using (22% alcohol, 40% glycerin and 38% water). ## **Combined effect of pH and solvents** The solvent affects the solubility of a weak electrolyte in a buffered solution in two ways: * The addition of alcohol to a buffered aqueous solution of a weak electrolyte increases the solubility of the un-ionized spices by adjusting the polarity of the solvent to a more favorable value. * Being less polar than water, alcohol, decrease the dissociation of weak electrolyte leading to decreased solubility of the drug. ## **Effect of Molecular Structure of Solute** Even a small change in the molecular structure of compound can have a marked effect on its solubility in a given liquid. ### **Example** * 1. The introduction of a hydrophilic hydroxyl group can produce a large improvement in water solubility more than 100 fold difference in solubility of phenol and benzene. * 2. Conversion of weak acid to it's sodium salt leads to greater degree of ionic dissociation with water. The reduction in aqueous solubility of parent drug by esterification as a result of change in the chemical structure. ## **Crystal characteristic and solubility** The difference in crystalline form of the same substance are known as Polymorphs. These differences are reflected in drugs properties including solubility. ### **Examples of drugs that exhibit polymorphism are: ** * 1. Steroids * 2. Barbiturates * 3. Sulphonamids ## **Particle size and shape of small particles** The solubility of a substance increases with decrease in the particle size. The reason is the change in the interfacial free energy. $log\frac{S}{S_o}=\frac{2yV}{2.303RTr}$ Where S is the solubility of small particles of radius r, $S_o$ is the normal solubility of solid, y is the surface tension, V is the molar volume(volume in cm³per mole of particles), R is the gas constant (8.314x107 erg/deg) and T is the thermal dynamic temperature. ### **Applications** * 1. The effect of particle size of solute is important in storage as small particle will dissolve and larger particles will remain in suspension. * 2. The occurrence of crystal growth by this mechanism is of particular important in the storage of suspensions intended for injection. ## **Complexes and solubility of drug** The solubility of a solute in a particular liquid may be increased or decreased by the addition of a third substance which forms an intermolecular complex with the solute. ### **Examples** * 1. The formation of the complexes between 3-aminobenzoic acid and various carboxylic acids leading to increased water solubility of 3-aminobenzoic acid. * 2. Complex formation as an aid to solubility in the preparation of solution of mercuric iodide in solution of potassium iodide. ## **Surface Active Agent and solubility** Surface active agents (amphiphilic) are molecules and ions that adsorbed at interface. Weakly acidic and basic drugs may be brought into solution by the solubilizing action of surface-active agents. ### **Examples** * 1- Polyoxyethylene sorbitan monolaurate (Tween 20) * 2- Polyoxyethylene sorbitan monooleate (Tween 80) * 3- sorbitan monolaurate (Span 20) * 4- sorbitan mono olealte (Span 80) * 5- Sodium lauryl sulfate ### **Applications** * The micellar solublizations of weak electrolytic drugs by aqueous solutions of the nonionic surfactant, polysorbate 80. * Solubilizing action of Tween 20 on peppermint oil in water. ## **Solubilizing agents** The solubility of poorly soluble drug can also be improved by various solubilizing materials. ### **Examples: ** * 1. PEG 400 is improving the solubility of hydrochlorthiazide. * 2. The aqueous solubility of the antimalarial agent halofantrine is increased by addition of caffeine and nicotinamide. ## **Specification for selecting solubilizing agent** * 1. Non-toxic. * 2. Miscible with the solvent (usually water). Compatible with the material to be solubilized. * 3. Free from disagreeable odour and taste. * 4. Relatively non-volatile. * 5. The amount is important as: * a) Large excess is undesirable can lead to toxic or reduced absorption. * b) Insufficient amount can lead to precipitation of the solute. ## **THE PHASE RULE** * 1. **The miscibility of liquids:** Miscibility of Liquids may be described by the use of Gibbs’ phase rule $F=C-P+2$ Where F is the number of degree of freedom i.e. independent variables (temperature, pressure and concentration) that must be stated to describe the system. C is the number of component and P is the number of phases. * 2. **Solubility of solid in liquids** The solubility of solid in liquids has also been described by Gibbs’ phase rule. In this the pressure is fixed at 1 atm and hence not applied. The equation becomes $F=C-P+1$