Physical pharmacy i third semester (unit-i) solubility of drug

Introduction of Physical Pharmacy, objective, Solubility of drugs, defination of Solution, solute, solvent, Saturated solution, unsaturated solution, supersaturated solution and solubility, Solubility expression,Mechanism of solute solvent interaction, polar solvent, nonpolar solvent and semipolar solvent

1. SEMESTER-III PHYSICAL PHARMACEUTICS-I INTRODUCTION Presented By : Miss. Pooja D. Bhandare Kandhar College of Pharmacy, Nanded

2. Introduction Physical pharmaceutics is the branch of pharmacy that concentrate on the application of physics and chemistry to study of pharmaceutics. In other words, study of effect of dosage forms at molecular level.

3. Objective Understand various physicochemical properties of drug molecules in the designing the dosage forms and in formulation development. Know the principal of chemical kinetics & to us them for stability testing and determination of expiry date formulation

4. Unit-I : Solubility of drug. Unit-II : State of matter and properties of matter Unit-III : Micromeretics Unit-IV : Complexation and Protein binding Unit-V : pH, Buffer and Isotonic solution

5. IIIrd Semesester B. pharmacy Physical Pharmaceutics-I Unit-I Solubility of drugs Presented by : Miss Pooja D. Bhandare (Assistant Professor) Kandhar college of Pharmacy, nanded

6. Definations Solution : Solution is a mixture of two or more components that forms a homogenous mixture. The component are referred to the solute and solvent. A solution is made by dissolving a solute in a solvent Solute : The substance usually present in lesser amount and getting dissolved in the solution Solvent : Solvent is a subcomponent in which solute is dissolve usually which is a greater amount.

7. Saturated Solution : A solution in which dissolved solute is in equilibrium with the undissolved solute or solid phase. Unsaturated solution : A solution containing the dissolve solute in a concentration less than saturated solution. Supersaturated Solution : A solution which contain more concentration of solute than the saturated solution

8. Solubility In a quantitative way It is the concentration of solute in a saturated solution at a certain temperature In a qualitative way It is the spontaneous interaction of two or more substances (solute & Solvent) to form a homogenous molecular dispersion Solubility is a intrinsic material property of the molecule while the Dissolution is the extrinsic property

9. Solubility of drugs depends on the physical and chemical properties of both the solute and solvent Temperature Pressure pH of the solution State of subdivision of the solute

10. Solubility expression I) Quantitative II) Qualitative USP exprerssion Molar solution Molal solution Mole Fraction Sparingly Soluble Percent by weight/ volume Percent by weight Percent by volume Soluble Very soluble Freely Soluble Slightly Solublr Very slightly soluble Practically insoluble

11. Terms Parts of solvent required per part of solute Very soluble Less than 1 Freely soluble From 1 to 10 Soluble From 10 to 30 Sparingly soluble From 30 to 100 Slightly soluble From 100 to 1000 Very Slightly soluble From 1000 to 10000 Practically insoluble More than 10000

12. USP expression : Number of mls of solvent dissolving 1 gm of solute (gm/ml) Molar solution : Number of moles of solute/1 litre of solution (mol/L) Molal solution : Number of moles of solute/ 1000gm of solvent Mole fraction : Mole fraction of (A) = Moles(A)/ sum of moles(A)+(B) Percent by weight : Number of gms of solute/100gms solution (%w/w) Percent w/v : Number of gms of solute/ 100ml solution(%w/w) Percent by volume : Number of mls of solute/100ml solution (%v/v) Quantitative

13. Mechanism of solute solvent interaction Solvent- solute interaction In pre or early formulation, selection of the most suitable solvent is based on the principle of “LIKE DISSOLVES LIKE” That is, a solute dissolves best in a solvent with similar chemical properties or two substances with similar intermolecular forces are likely to be soluble in each others Polar solutes dissolves in polar solvents. Example Salt and sugar dissolve in water. Non polar solutes dissolve in nonpolar solvent. Example Naphthalene dissolves in benzene

14. If the solvent is A & the solute is B and the forces of attraction are represented by A-A, B-B and A-B. One of the following conditions will occur : If A-A >> A-B The solvent molecules will be attracted to each other & the solute will be excluded. Example Benzene & water, where benzene molecules are unable to penetrate the closely bounds water aggregates. If B-B >> A-A The solvents will not be able to break the binding forces between solute molecules. Example NaCl in benzene, where the NaCl crystal is held by strong electrovalent forces which can not be broken by benzene. If A-B>> A-A or B-B, or the three forces are equal then solute will form a solution. Example NaCl in Water.

15. Sr. No Nature of Solvents Mechanism of solubility Example 1 Polar High dielectric constant H- bond formation Dipole interactions Water + ethanol 2 Non -Polar Weak van der waal’s forces Fats, oils, alkaloidal bases + CCL4, benzene 3 Semi- Polar Induce certain degree of polarity Acetone increases solubility of ether in water

16. Polar solvent The solubility of drug is due in large measure to the polarity of the solvent, that is, to its dipole movement. Polar solute dissolve ionic solvent and other polar substance Hildbrand findings The ability of the solute to form hydrogen bonds is a far more significant factor than is the polarity as reflected in a high dipole moment. Water dissolves phenols, alcohols, aldehyde, ketone, amines and other oxygen & nitrogen containing compounds that can form hydrogen bonds with water.

17. The solubility of substance also depends on structural features such as the polar to the non polar group of the molecule. Acidic and basic characters also contributes to the interaction in solution. As the nitrogen of a nonpolar chain of an aliphatic alcohol increases, the solubility of the compounds in water decreases.

18. Polar groups Straight chain monohydroxy alcohol, aldehydes, ketone and acids with more than four or five carbons cannot enter into the hydrogen bonded structure of water. Branching e.g., t-butyl alcohol and n-butyl alcohol

19. Non-polar solvent Non-polar solvents are unable to reduce the attraction between the ions of strong and weak electrolytes because of the solvent low dielectric constant . The are unable to form hydrogen bonds with non electrolytes (aprotic solvent). Non-polar solute and solvent are miscible due to similar internal pressure through induced dipole interactions. The solute molecules are kept non polar solvent through weak van der Walls-London type of forces . Example: solution of oils& fats in carbon tetrachloride or benzene Polyetylene glycol 400 and castor oil

20. Semi-polar solvents Semi polar solvents such as ketones can induce a certain degree of polarity in non-polar solvent molecule. For example, benzene which is readily polarizable, becomes soluble in alcohol They can act as a intermediate solvents to bring about miscibility of polar and non-polar liquids. Example: acetone increases solubility of ether in water, Propylene glycol has been shown to increases the mutual solubility of water and peppermint oil and water and benzyl benzoate.