Colligative Properties L1 2024 student.pdf

Colligative Properties and Tonicity Calculations Lecture 1 Jenny Dolzadelli/Dr Victor Chuang CRICOS Provider Code 00301J  COMMONWEALTH OF AUSTRALIA C...

Colligative Properties and Tonicity Calculations Lecture 1 Jenny Dolzadelli/Dr Victor Chuang CRICOS Provider Code 00301J  COMMONWEALTH OF AUSTRALIA Copyright Regulation 1969 WARNING This material has been copied and communicated to you by or on behalf of Curtin University of Technology pursuant to Part VB of the Copyright Act 1968 (the Act) The material in this communication may be subject to copyright under the Act. Any further copying or communication of this material by you may be the subject of copyright protection under the Act. Do not remove this notice CRICOS Provider Code 00301J  Learning Outcomes At the end of these lectures, students should be able to: Identify and discuss the colligative properties of solutions Explain and differentiate between iso- osmoticity and isotonicity Explain the importance of isotonicity for a range of pharmaceutical preparations Perform accurate calculations related to tonicity of pharmaceutical preparations CRICOS Provider Code 00301J  References Allen LV (Ed). Remington: the Science and Practice of Pharmacy. 22nd ed. London: Pharmaceutical Press; 2013. Ansel HC. Pharmaceutical Calculations.14th ed: Lippincott Williams & Wilkins; 2013. Australian Pharmaceutical Formulary and Handbook. 24th ed: Pharmaceutical Society of Australia; 2018. Carter SJ (Ed). Cooper and Gunn’s Dispensing for Pharmaceutical Students. 12th ed. London: Pitman Medical; 1975. Florence AT, Attwood D. Physicochemical Principles of Pharmacy. 5th ed: Pharmaceutical Press; 2011. Flynn GL & Roberts MS. Physical and Biophysical Foundations in Pharmacy Practice – issues in drug delivery. Houston:Blausen Medical; 2015 CRICOS Provider Code 00301J  Colligative Properties Physical properties of solutions that are dependent on the NUMBER of dissolved non-volatile solute species. Include: Vapour pressure lowering Boiling point elevation Freezing point depression Osmotic pressure Osmotic pressure is of particular significance to pharmacists CRICOS Provider Code 00301J  Colligative properties When a solute is dissolved in a liquid (eg water) the solvent molecules are more disordered than in the pure solvent. Entropy of the solvent (and the system) has increased, so the solvent will have a lower free energy. ΔG = ΔH – TΔS ie increase in S (entropy)  decrease in G (G = free energy; H = enthalpy; S = entropy) CRICOS Provider Code 00301J  Vapour Pressure Lowering When a nonvolatile solute is combined with a solvent, the vapour above the solution is provided solely by the solvent Vapour pressure of a solution is lower than that of the solvent – solvent has lower free energy and needs more energy to vaporise Molecules of solvent at the surface are replaced with molecules of solute – lowering the tendency of solvent molecules to escape. The reduction in vapour pressure is proportional to the relative number of the solute molecules CRICOS Provider Code 00301J  Vapour Pressure Lowering Raoult’s law states that the vapour pressure, P1, of a solvent over a dilute solution is equal to the vapour pressure of the pure solvent, 𝜌𝜌1o, multiplied by the mole fraction of solvent in the solution, X1. P1 = X1𝜌𝜌1o The relative vapour pressure lowering depends only on the mole fraction of the solute. X1 + X2 = 1 P1 = (1 - X2) 𝜌𝜌1o ∆P = X2 𝜌𝜌1o (X2 = mole fraction of solute) P1 = 𝜌𝜌10 - 𝜌𝜌10 X2 𝜌𝜌10 - P1 = 𝜌𝜌10 X2 CRICOS Provider Code 00301J  Elevation of Boiling Point Boiling point is the temperature at which the vapour pressure of the liquid becomes equal to atmospheric pressure. Because vapour pressure of a solution is lower than that of the solvent, solutions boil at a higher temperature. The effect is proportional to the number of dissolved species (ie concentration). If a solute is dissolved in the solvent, the solution acquires a new boiling-point that is at a higher temperature. CRICOS Provider Code 00301J  Elevation of Boiling Point Pressure (mm Hg) 760 P° Solvent ∆P P ∆Tb = Kbm ∆ Tb : boiling point Solution elevation, Kb : molal elevation constant or T ebullioscopic Temperature T0 constant, m : molality ∆T b CRICOS Provider Code 00301J  Depression of Freezing Point Freezing point (= melting point) of a solvent is the temperature at which solid and liquid phases coexist at atmospheric pressure The freezing point of a solution is the temperature at which liquid solution is in equilibrium with solid solvent - lower than that of the pure solvent. Depression of freezing point is proportional to the number of solute species in solution ∆Tf = Kfm ∆ Tf : freezing point depression, Kf : molal depression constant/ cryoscopic constant, m : molality CRICOS Provider Code 00301J  Depression of Freezing Point/Elevation of Boiling Point of Water by a solute Pure water-pure Solution-ice Pure ice equilibrium equilibrium water Solution 760 Pressure (mm Hg) Liquid Solid Triple point 4.58 Vapor T T0 0.0098 100 T Temperature (° C) ∆T f ∆T b CRICOS Provider Code 00301J  Osmosis Substances in solution diffuse from areas of high concentration to areas of lower concentration. If a solution is separated from a solvent by a semi-permeable membrane (one through which only solvent molecules can pass), then only the solvent molecules can diffuse to equalise concentration (activity) This process is OSMOSIS CRICOS Provider Code 00301J  Osmotic pressure Osmosis is defined as the passage of the solvent into a solution through a semipermeable membrane. Osmotic pressure is the pressure which must be applied to a solution to prevent water from flowing in via a semipermeable membrane. Osmotic pressure is proportional to the number of dissolved species in solution. CRICOS Provider Code 00301J  Osmosis Osmotic pressure = pressure applied to prevent osmosis CRICOS Provider Code 00301J  Osmotic Pressure Osmotic pressure (π) is of interest to pharmacists as biological membranes act as (imperfect) semi-permeable membranes. Undesirable osmotic movement of water through biological membranes may cause serious consequences for patients. Osmotic effects can also be exploited for therapeutic effect. CRICOS Provider Code 00301J  Van’t Hoff Equation π V = nRT π = osmotic pressure V = volume of the solution n = number of moles of solute R = universal gas constant T = absolute temperature (K). Van’t Hoff equation only strictly applies to dilute solutions – deviations occur with more concentrated solutions. CRICOS Provider Code 00301J  Van’t Hoff equation for osmotic pressure Van’t Hoff equation can be expressed as: π V = nRT π = (n/V)RT π = cRT c is the concentration of the solute in moles/litre(molarity). CRICOS Provider Code 00301J  Morse Equation Morse et al showed that when the concentration is expressed in molality rather than molarity, the results compare more closely with the experimental findings: π π = mRT π What is molality? At low concentrations, molarity ≅ molality For electrolytes, π = imRT, where i = number of ions formed when the solute dissolves in water. CRICOS Provider Code 00301J  Osmoticity When two solutions, separated by a semi- permeable membrane, each have equal concentrations of dissolved species, no net movement of solvent will occur and the solutions are said to be “ISO-OSMOTIC” or “ISOSMOTIC”. Non-electrolytes will dissolve to produce a single species, however, ionic species dissociate to produce two or more species. The Osmol is a measurement of the number of dissolved species CRICOS Provider Code 00301J  Osmols Osmotic pressure is proportional to the total number of entities in solution. The unit used to measure osmotic concentration is the osmole (Osmol), or more commonly, milliosmole (mOsmol). Osmol = weight in grams of a solute that is osmotically equivalent to a mole of non-electrolyte. The number of Osmols of a solute equals the number of moles multiplied by the number of species produced on dissolution. Osmol/L = M x no: of dissolved species For dextrose, a nonelectrolyte, 1 mmol represents 1 mOsmol. CRICOS Provider Code 00301J  Osmols For electrolytes, the total number of species in solution depends on the degree of dissociation of the substance in question. Assuming complete dissociation: 1 mmol of NaCl represents 2 mOsmol (Na+ + Cl-) of total entities, 1 mole of NaCl forms 2 Osmoles (1 mole Na+ + 1 mole Cl-). 1 mmol of CaCl2 represents 3 mOsmol (Ca2+ + 2Cl-) of total entities. 1 mole of glucose (not ionised) forms 1 Osmole of solute CRICOS Provider Code 00301J  Osmolality and Osmolarity Osmolality Osmolarity Osmolality is defined Osmolarity is defined as the mass of as the mass of solute solute that when which, when dissolved in 1 kg of dissolved in 1 litre of water will exert an solution, will exert osmotic pressure an osmotic pressure equal to that exerted equal to that exerted by a mole of an ideal by a mole of an ideal un-ionised un-ionised substance substance dissolved dissolved in 1 litre of in 1 kg of water. solution. CRICOS Provider Code 00301J  Osmolality and Osmolarity 1 mole of NaCl weighs 58.2g, 1 Osmol of NaCl weighs 58.2g/2 ie 29.1g. Mass = Osmol x MW no: species A 1 molal solution of NaCl will have (approximately) twice the osmolality (osmotic pressure) as a 1 molal solution of glucose. A 1 molar solution of NaCl will have (approximately) twice the osmolarity (osmotic pressure) as a 1 molar solution of glucose. CRICOS Provider Code 00301J  Example A solution contains 5% of anhydrous dextrose in water for injection. What is the concentration in mOsmols per litre? MW Dextrose anhydrous = 180 CRICOS Provider Code 00301J  Answer: Dextrose is a non-electrolyte and dissolves to produce a single species Molecular weight of anhydrous dextrose = 180 1mmol of anhydrous dextrose (180mg) = 1mOsmol 5% solution contains 50g or 50,000 mg/L; 50,000mg /180 = 278 mOsmol/L Osmol/L = M x no: of dissolved species Or (50,000mg /L) x (1mOsmol/180mg) = 278 mOsmol/L CRICOS Provider Code 00301J  Example 2 Calculate the osmolarity of the following solution: NaCl 3.8g 7.6g MW NaCl = 58.4 CaCl2.2H2O 0.9g 1.8g MW CaCl2.2H2O = 147 Purified Water to 500mL to 1000mL Osmol/L = mol/L x number of dissociated species = 7.6 x 2 + 1.8 x 3 58.4 147 = 0.260 + 0.036 Osmol/L = 0.296 Osmol/L = 296 mOsmol/L CRICOS Provider Code 00301J  Osmotic Pressure Whenever there is an imbalance in the concentration of dissolved species (to which a biological membrane is impermeable) on either side of the membrane, water will move through the membrane to correct the imbalance. These effects can cause temporary or permanent damage to red blood cells, irritation to vascular and ocular tissue, irritation to nasal tissue and interference with cilial action as well as effects on the gastrointestinal mucosa. CRICOS Provider Code 00301J  Isotonicity Body fluids are generally 280-300mOsmol/L Rendering a solution iso-osmotic (aka isosmotic) with a body fluid means that it contains the same number of units/volume of solute as the body fluid. In theory, no net passage of water would be expected across the biological membrane. BUT biological membranes are NOT perfect semi- permeable membranes and some solutes are able to pass through them. An isotonic solution is one which results in no net movement of water across the biological membrane. Is the solution in Example 2 iso-osmotic with body fluids? CRICOS Provider Code 00301J  Tonicity A solution that is iso-osmotic with body fluids may not necessarily be isotonic. Biological membranes are permeable to some small solutes (eg urea, propylene glycol, ammonium chloride, glycerol). There are some differences in permeability of different membranes (eg rbc permeable to boric acid, but mucous lining of eye is not) A solution that is not isotonic is “PARATONIC”. It may be hypotonic (containing a lower concentration of dissolved species) or hypertonic (containing a higher concentration of dissolved species) CRICOS Provider Code 00301J  Importance of Isotonicity RED BLOOD CELLS When red blood cells are placed in a solution that is hypotonic, water moves into the cells  swelling and lysis of the cells. When red blood cells are exposed to a solution that is hypertonic, water moves out of the cells  shrinking and crenation of the cells. This is reversed when the tonicity of the solution is restored to isotonicity. https://curtin.h5p.com/content/1291673044652688909 SOURCE: http://www.youtube.com/watch?v=Y_w07A7chnk CRICOS Provider Code 00301J  Effect on Red Blood Cells of Solutions of varying Tonicity Source: Sinko PJ Martin’s Physical Pharmacy and Pharmaceutical Sciences (6th ed) Philadelphia: Lippincott Williams & Wilkins; 2011, p 175 CRICOS Provider Code 00301J  Flynn & Roberts (2015) CRICOS Provider Code 00301J Tonicity of Parenteral Formulations Intravenous Hypotonic IV infusions  haemolysis and water invasion into other body cells (which can lead to water intoxication – convulsions and oedema - pulmonary, cerebral). Renal failure may develop from haemoglobinaemia. Hypertonic  crenation of rbcs. Small volumes administered slowly into fast flowing vein rapidly diluted in blood stream  minimal problems. Large volumes delivered too rapidly can cause osmotic diuresis ( dehydration) CRICOS Provider Code 00301J  Total Parenteral Nutrition (TPN) – hypertonic, large volume – administered slowly via central vein. Hypertonic IV given via a vein with slow circulation may also irritate the blood vessel walls  occlusion Intrathecal Paratonic solutions disrupt osmotic pressure  headache, vomiting more serious neurological consequences eg seizures Intrathecal injections must be strictly isotonic Intramuscular Slightly hypertonic encourages dilution by tissue fluids  rapid absorption CRICOS Provider Code 00301J Nasal and Ophthalmic Preparations Nasal Instillations that are not isotonic irritate the nasal mucosa and interfere with cilial action. Ophthalmic preparations should usually be isotonic to avoid irritation to the mucous membranes and flushing due to tear formation. CRICOS Provider Code 00301J  Enteral Delivery Enteral feeding solutions are hyperosmotic – if excessively hyperosmotic, osmotic diarrhoea and mucosal damage can occur (individual variation in tolerance). In premature infants, high tonicity of enteral feeds associated with necrotising enterocolitis Oral liquid medications are often highly hyperosmotic – when given to premature infants can cause pneumotosis intestinalis. Can only reduce the tonicity of a hypertonic solution by dilution. CRICOS Provider Code 00301J  The Egg Experiment Egg (without shell) in Egg in shell – initial Egg (without shell) in glucose syrup size water CRICOS Provider Code 00301J Mock Exam Questions Give THREE examples of pharmaceutical preparations that should be isotonic and explain the reasons for this requirement. Differentiate between iso-osmoticity and isotonicity. Explain how a small volume of a hypertonic injection may be administered safely. Describe the problems associated with intravenous infusion of large volumes of hypotonic solutions. Briefly describe the FOUR colligative properties of solutions. CRICOS Provider Code 00301J