Solubility of drugs

Solubility of drugs

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  Solubility of drugs AssistantProfessor Miss. Priya P. Mane Deshmukh College of Pharmacy , Paniv
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  Definition:- • SOLUBILITY “ itis ability of one substance to fully dissolved in another substance under specified condition.” “ The concentration of a substance (solute) that dissolves in a given volume of solvent at a certain temperature to form a homogenous solution.” “ The spontaneous interaction of two or more substances to form a homogenous molecular dispersion.” Types of Solubility:- 1) Intrinsic Solubility 2) Apparent Solubility
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  • Solute: acomponent which dissolved in the solvent, present in less amount in the solution. • Solvent: a component in which solute is dissolved, present in more amount than solute. • Solution: A system in which solutes are completely dissolved in solvent & form a homogenous molecular dispersion. • Saturated solution: Solution in which the solute in solution is in equilibrium with solid phase. • Unsaturated solution/ sub-saturated solution : Solution containing dissolved solute in concentration below that necessary for complete saturation. • Supersaturated solution: Solution containing more of the dissolved solute than it would normally contain.
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  1. Saturated Solution- holds the maximum amount of solute 2. Unsaturated Solution – holds less than the maximum amount of solute 3. Supersaturated Solution – holds more than the maximum amount of solute
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  Solubility expression:- 1. Gm/ml 2.Molarity 3. Molality 4. Normality 5. %w/w 6. %v/v 7. %w/v
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  Mechanism of solutesolvent interactions
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  Mechanism of Solutesolvent interaction Steps of solid going into solution. 1. Step 1: Hole open in the solvent 2. Step 2: One molecule of the solid breaks away from the bulk 3. Step 3: The solid molecule is enter into the hole in the solvent
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  Types of interaction 1.solvent– solvent interaction 2. solute – solute interaction 3. solvent solute interaction ΔH sol = ΔH 1 + ΔH 2 + ΔH 3
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  • If thesolvent 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: 1. 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 bound water aggregates. 2. If B-B >> A-A The solvent 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 cannot be broken by benzene. 3. If A-B >> A-A or B-B, or the three forces are equal The solute will Form a solution. Example: NaCl in water.
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  Solvation / Dissolution •“ Interaction of a solute with the solvent, which leads to stabilization of solute species by surrounding it with solvent in the solution” • +ve solvation energy= endothermic dissolution • -ve solvation energy= exothermic dissolution
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  • Solvation processaffected by hydrogen bonding and van der Waals force • Kinetic process and rearranging solvent –solute mole. Into solvation complex to distribute solute mole. within the solvent • Insoluble solute mole. Interaction solute mole. Break parts Solvation ( ion exchanges) by the solvent • Solvants :- a compound that froms between a solute and its solvent • Hydrates:- ( ammoniates, alcoholates,etherates) • Solvation number:- (mol/l,mg/ml)
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  Association “ Chemical reactionin which the opposite electric charge ions come together in solution & form a distinct chemical entity” • Classification according to nature of interaction: 1. Contact 2. Solvent shared/Solvent separated 3. Fully solvated
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  Biopharmaceutics Classification System (BCS)
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  Classification of solvents:- 1.Polar solvents 2. Non polar solvents 3. Semi polar solvents
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  Polar solvents • Thesolubility of a drug is due in large measure to the polarity of the solvent, that is, to its dipole moment. Polar solvents dissolve ionic solutes and other polar substances. • 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 and other oxygen & nitrogen containing compounds that can form hydrogen bonds with water. • The solubility of a substance also depends on structural features such as the ratio of the polar to the nonpolar groups of the molecule. • As the length of a nonpolar chain of an aliphatic alcohol increases, the solubility of the compound in water decreases • Straight-chain monohydroxy alcohols, aldehydes, ketones, and acids with more than four or five carbons cannot enter into the hydrogenbonded structure of water and hence are only slightly soluble.
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  • Hydrogen bondingis the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen Dipole-dipole forces are electrostatic interactions of permanent dipoles in molecules.
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  Non polar solvents •Non-polar solvents are unable to reduce the attraction between the ions of strong and weak electrolytes because of the solvents' low dielectric constants. • They are unable to form hydrogen bonds with non electrolytes. • Non polar solvents can dissolve non polar solutes through weak van der Waals forces • Example: solutions of oils & fats in carbon tetrachloride or benzene. • Polyethylene glycol 400 • Castor oil
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  Semi polar solvents •Semi polar solvents, such as ketones can induce a certain degree of polarity in non polar solvent molecules. • For example, benzene, which is readily polarizable, becomes soluble in alcohol • They can act as intermediate solvents to bring about miscibility of polar & non polar liquids. • Example: acetone increases solubility of ether in water. • Propylene glycol has been shown to increase the mutual solubility of • water and peppermint oil and of water and benzyl benzoate
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  Examples solvents andsolutes
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  FACTORS INFLUENCING SOLUBILITY •1. Temperature • 2. Nature of solvent ( like dissolves like) • 3. Pressure • 4. pH • 5. Particle size • 6. Crystal structure • 7. Molecular structure • 8. Solute- solvent interactions • 9. Addition of substituent • 10. Common ion effect • 11. Solubilizing agents
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  SOLUBILITY OF LIQUIDSIN LIQUIDS • 1. Completely miscible liquids: E.g. Water+ ethanol, Glycerine+ Alcohol, benzene+ CCL4 • 2. Partially miscible liquids: E.g. Phenol+ water. • 3. Completely immiscible liquids: E.g. Mercury+ water.
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  • RAOULT’S LAW •“The partial pressure (Pi) of each component in a solution is equal to the mole fraction of the component & the vapour pressure of the pure component” Pi = xP Or P = pAxA + pBxB IDEAL SOLUTIONS “ Solutions which obey Raoult’s law in all the solute composition in a solvent”
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  • REAL/ NONIDEAL SOLUTIONS • “Solutions which do not obey Raoult’s law over entire range of composition” Negative deviation PA < Xa P △H < 0 △V < 0 Positive deviation PA > Xa P △H > 0 △V > 0
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  SOLUBILITY OF GASESIN LIQUIDS • Henry’s law: ‘Solubility is directly proportional to partial pressure of gas at a constant temperature’. S= KP
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  Factors affecting gasin liquids • Effect of pressure • Effect of temperature • Effect of electrolytes and non electrolytes • Effect of chemical reaction
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  NERNS’T DISTRIBUTION LAW (PARTITION COEFFICIENT) • “ If a solute distributes between two immiscible solvents at a constant temperature then the ratio of its concentration in two solvents is a constant value”. • K= C1/ C2
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  DIFFUSION
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  • •water solubledrug (ionized or polar) is readily absorbed via aqueous channels or pores in cell membrane. • •Lipid soluble drug (nonionized or non polar) is readily absorbed via cell membrane itself.