Solubility and Related Phenomena (Part-3) PDF

Solubility and Related Phenomenon (Part-3)  Solubility and Related Phenomenon  Solutions of pharmaceutical importance include: 1. Gases in liquids 2. Liquids in liquids 3. Solids in liquids 4. Solid in solid 1. Solubility of Gas in Liquids: The solubility of gases in liqu...

Solubility and Related Phenomenon (Part-3)  Solubility and Related Phenomenon  Solutions of pharmaceutical importance include: 1. Gases in liquids 2. Liquids in liquids 3. Solids in liquids 4. Solid in solid 1. Solubility of Gas in Liquids: The solubility of gases in liquid is the maximum amount of gas that can dissolve into a liquid. The solubility of gases in liquids is highly affected by the temperature, pressure, and also the nature of the solute and the solvent. a. Temperature: solubility decreases as temperature increases, The physical reason for this is that when most gases dissolve in solution, the process is exothermic. 2 Solubility and Related Phenomenon This means that heat is released as the gas dissolves. Increased temperature causes an increase in kinetic energy. The higher kinetic energy causes more motion in the gas molecules which break intermolecular bonds and escape from solution. 3  Solubility and Related Phenomenon b. Pressure: Liquids and solids do not exhibit a change in solubility with changes in pressure. Gases show a significant increase in solubility with an increase in pressure. 4  Solubility and Related Phenomenon  Henry's Law: states that the solubility of a gas in a liquid at a constant temperature is directly proportional to the pressure of the gas above the liquid. C: is the concentration of dissolved gas at equilibrium, P: is the partial pressure of the gas, and K: is the Henry’s law constant, which must be determined experimentally for each combination of gas, solvent, and temperature.  LIMITATIONS OF HENRY'S LAW : Henry’s law is valid only under the following conditions only when: 1. The pressure of the gas in not too high. 2. The temperature is not too law. 3. The gas should not undergo dissociation in solution. 4. The gas should not undergo any reaction with the solvent. 5 Solubility and Related Phenomenon 6  Solubility and Related Phenomenon  APPLICATION 7 Solubility and Related Phenomenon 8  Solubility and Related Phenomenon 2. Solubility of Liquids in Liquids  Frequently two or more liquids are mixed together in the preparation of pharmaceutical solutions.  For example, alcohol is added to water to form hydroalcoholic solutions of various concentrations;  Volatile oils are mixed with water to form dilute solutions known as aromatic waters;  Various fixed oils are blended into lotions, sprays, and medicated oils.  Liquid–liquid systems can be divided into two categories according to the solubility of the substances in one another: a. Complete miscibility and b. Partial miscibility. 9 Solubility and Related Phenomenon 10  Solubility and Related Phenomenon 3. Solubility of Solid in Liquids  Systems of solids in liquids include the most frequently encountered and probably the most important type of pharmaceutical solutions. They react with strong acids and bases and, within definite ranges of pH, exist as ions that are ordinarily soluble in water.  Many important drugs belong to the class of weak acids and bases.  The solubility of a solid in a liquid cannot be predicted in a satisfactory manner, except for ideal solutions, because of the complicating factors that must be taken into account.  Factors affecting solubility of solid in liquid: 11  Solubility and Related Phenomenon a. Temperature: 12 Solubility and Related Phenomenon 13 Solubility and Related Phenomenon 14  Solubility and Related Phenomenon B. The influence of solvents on the solubility of drugs:  Examples on water miscible solvents; glycerol, propylene glycol, ethyl alcohol. 15 Solubility and Related Phenomenon 16 Solubility and Related Phenomenon 17 Solubility and Related Phenomenon 18  Solubility and Related Phenomenon c. The influence of pH on aqueous solubility: 1. Acidic drugs: are less soluble in acidic solutions than Alkaline solutions because the predominant undissociated species cannot interact with water molecules to the same extent as the ionized form which is readily hydrated. 2.Basic drugs: are more soluble in acidic solution where the ionized form of the drug is predominant. 3.Amphotric drugs: have both basic and acidic characteristics such amino acids. 19 Solubility and Related Phenomenon 20 Solubility and Related Phenomenon 21 Solubility and Related Phenomenon 22  Solubility and Related Phenomenon d. The influence of Particle size on the solubility of drugs: Particle size plays a critical role in determining the solubility rate. Small particles dissolve more rapidly due to their more efficient interaction and increased surface area, while large particles dissolve more slowly. 23  Solubility and Related Phenomenon e. The influence of SAA on aqueous solubility: 24 Solubility and Related Phenomenon 25 Solubility and Related Phenomenon 26 Solubility and Related Phenomenon 27 Solubility and Related Phenomenon 28 Solubility and Related Phenomenon 29 Solubility and Related Phenomenon 30 Solubility and Related Phenomenon 31 Solubility and Related Phenomenon 32 Solubility and Related Phenomenon 33  Solubility and Related Phenomenon  Distribution of solutes between immiscible solvents  The movement of molecules from one phase to another is called partitioning.  If two immiscible phases are placed adjacent to each other, the solute will distribute itself between two immiscible phases until equilibrium is attained, therefore no further transfer of solute occurs.  When a substance is add in excess quantity in two immiscible solvents, it distributes itself between two liquid phases so that each becomes saturated. 34  Solubility and Related Phenomenon  Partition Coefficients:  The partition coefficient (Kpc) is the ratio of the concentrations of a solute in two different immiscible solvents in contact with each other when equilibrium has been established (at a particular temperature).  If C1 and C2 are the equilibrium concentrations of the substance in solvent1 and solvent2 , the equilibrium expression becomes: 𝐶1 𝐾𝑝𝑐 = 𝐶2  the equilibrium constant is known as the distribution ratio, distribution coefficient or partition coefficient. 35  Solubility and Related Phenomenon  For example, methylamine (CH3NH2) is dissolved in two immiscible solvents: Water. An organic solvent. The partition coefficient is the ratio of methylamine molecules in the organic and aqueous layer once equilibrium has been established. 36 Solubility and Related Phenomenon 37 Solubility and Related Phenomenon 38  Solubility and Related Phenomenon  General Features:  Drugs partition themselves between the aqueous phase and lipophilic membrane.  If the partition coefficient of drug is more than one it is more lipophilic.  If the partition coefficient of drug is less than one it is less lipophilic.  It is a measure of how well substance partitions between lipid and water.  partition coefficients have no units. 39  Solubility and Related Phenomenon  Limitation:  Dilute solutions: the concentration of solute must be low in two solvents. This law does not holds good when the concentrations are high.  Constant temperature: temperature should be kept constant throughout the experiment, since solubility is dependent on temperature.  Same molecular state: Solute must be in the same molecular state in both the solvents. This law does not hold, if there is association or dissociation of solute molecules in one of the solvents.  Equilibrium concentration: this is achieved by shaking the mixture for longer time. 40