Summary

This document provides a lecture on the phases in pharmaceuticals. It discusses the concepts of phase equilibria and types of phase diagrams including the Gibbs phase-rule and examples.

Full Transcript

Phases in pharmaceuticals Phases: states of matter, e.g. solid, liquid, gas Phase: homogenous portion of physical material bounded by interfaces A dosage formulation (medicine) will typically contain multiple phases and components Need to understand the factors determining the extent a...

Phases in pharmaceuticals Phases: states of matter, e.g. solid, liquid, gas Phase: homogenous portion of physical material bounded by interfaces A dosage formulation (medicine) will typically contain multiple phases and components Need to understand the factors determining the extent and stability of the differing phases Pharmaceutically, can have gas phases, can have multiple liquid phases and can have multiple solid phases Phase equilibria Equilibrium between phases can be understood in terms of G = H − TS The phase with the lowest free energy G at temperature T is the most stable at that T For solid phases – enthalpy H is large and −ve (bonding between molecules) – entropy S is small (low disorder) – Hence at low temperatures T, solids tend to be the most stable phase For gas phases – Enthalpy H is close to 0 (no bonding between molecules) – entropy S is large and +ve (high disorder) – gases most stable at high T Liquid phases in between G as a function of T for a pure substance (i.e. 1 component) Tfus: temperature of G Tfus melting/fusion Tvap Where lines intersect, G = 0 T (free energies of both phases equal) Tvap: temperature of vaporisation Mixtures of phases and components Say have C components and P phases at equilibrium Each component can be present in each phase Can vary temperature (T) and pressure (P) How much freedom, i.e., flexibility, is there to change parameters without producing new phases or losing phases? The Phase Rule (Gibbs) gives the number of degrees of freedom (F) possible The Phase Rule F=C−P+2 (“+ 2” allows for variation in temperature and pressure) F: no. of degrees of freedom; C: no. of components; P: no. of phases One component, three phases in equilibrium: F = 0 (triple point) One component, two phases in equilibrium: F=1 Can use Phase Diagrams to illustrate which phases are stable under specific conditions General phase diagram for a pure substance (i.e., one component) Shows which phase (solid, liquid or vapour) is the most stable at pressure P and temperature T Triple points; three phases at F=C−P+2 Critical point equilibrium C = 1; P = 3; F = 0 Pressure (bar) Water: 0.01 °C, 6.1 mbar Solid Carbon dioxide: −57 °C, 5.1 Liquid bar Critical points: above which substance exists as supercritical Triple Vapour fluid point (combining aspects of liquid and Temperature (ºC) gas phases) For carbon dioxide: 31.1 °C, 73.8 bar Two component phase diagram To give a 2D plot, data at constant pressure, plot composition vs. temperature Use ‘reduced phase rule’: F = C − P + 1 (fixed pressure P) Temperature (T) Liquid Four regions Two components here All liquid (higher T) called A and B All solid (lower T) Along the ‘x axis’ is Two regions of solid suspended in liquid + solution shown composition in liquid + solid B solid A One has solid A (at higher A%) terms of %A and %B I.e. 100%A/0%B to The other solid B (at higher B%) Solid 0%A/100%B One point (of fixed T and ‘y axis’: temperature (T) composition) at which liquid and 100% A 100% B both solids are in equilibrium: the eutectic point Can only be measured empirically Eutectic point (is characteristic of the system) A system matching the above phase diagram is known as a simple eutectic system Example of a simple eutectic system Example: Naphthalene (C10H8) / Benzene (C6H6) Note: same features as the general diagram (i.e. four regions: all liquid (higher T), all solid (lower T), two regions of solid suspended in solution, one has solid benzene (at higher benzene%), the other solid naphthalene (at higher naphthalene%); one point (ca. −12 °C, 80% C6H6, 20% C10H8) at which liquid and both solid in equilibrium: the eutectic point Note terms ‘Liquidus’ (all liquid above) and ‘Solidus’ (all solid below) Point y: 50%C6H6/50% C10H8 at 60 °C: solution Cool to 10 °C (point z), after an indefinite time, have solid C10H8 suspended in a solution of mostly benzene Ratio of masses of solid and solution given by the lever rule: Tutorial: Phase diagrams The following thermal analytical data was obtained on mixtures of paracetamol and citric acid (Klimova and Leitner, Thermochim Acta, 2012, 59) Using graph paper, construct a binary phase diagram for the paracetamol/citric acid system Label each region of the diagram and estimate the composition at the eutectic point Note: m.p. paracetamol = 169 ◦C ; m.p. citric acid = 154 ◦C Mole fraction 0.1 0.2 0.3 0.4 0.6 0.8 0.9 paracetamol Solidus temp / ◦C 124 123 122 122 122 123 123 Liquidus temp / ◦ C 151 147 142 137 140 159 164 Mixtures of liquids (A and B) Common in dosage formulation In the pure liquids, A-A and B-B interactions only In the mixture, can also have A-B interactions Number of phases depends on the relative strengths of the A-A/B-B vs. A-B interactions Temperature dependent Two liquids; upper critical temperature (constant P) 1 liquid phase A-B comparable with A-A, B-B Upper critical temperature Temperature 2 liquid phases A-A and B-B stronger than A-B b c d a 0% A 100% A 100% B 0% B a b: A and B fully miscible, solution of A in B b c: two separate liquid phases; both saturated solutions c d: A and B fully miscible, solution of B in A Examples: hexane/aniline, hexane/nitrobenzene Two liquids; lower critical temperature (constant P) A-A and B-B stronger than A-B 2 liquid phases Temperature Lower critical temperature 1 liquid phase A-B comparable with A-A, B-B 0% A 100% A 100% B 0% B Can occur when A-B involves complex formation Triethylamine/water, paraldehyde/saline (paraldehyde enema) Three component systems Can use triangular (ternary) phase diagrams Constant T and P Components 1, 2 and 3 Apices represent pure components Points on sides: 2 components only At point o, composition: 1:2:3 = oa:ob:oc Alcohol (or surfactant), oil and water systems Alcohol Const. T and P Water/alcohol or oil/alcohol a fully miscible in all proportions Oil/water partially miscible only 1 phase p z w y x b o c Oil q Water 2 phases, one of composition x, the other of composition y xy and wz are tie lines (empirically determined) Upper critical point p Tutorial Shown below is a ternary phase diagram for an oil/water/surfactant system at a set temperature and pressure. State the composition of the system at points A, B and C. Estimate the composition of the system at point D. State the number of phases present at points E and F. Ternary phase diagrams using triangular graph paper A: 50% solubilizate, 30% water, 20% surfactant B: 60% surfactant, 40% solubilizate, 0% water Line represents dilution of the above with water Tutorial Data given below for a system of oil, water and alcohol at 25 °C On triangular graph paper, mark in points corresponding to: – Pure oil, pure water, pure alcohol – The five compositions given in the table Sketch in an estimation of the boundary between the region of one liquid phase and the region of two liquid phases One liquid phase Two liquid phases % oil 80 40 10 60 30 % water 10 40 80 30 60 % alcohol 10 20 10 10 10

Use Quizgecko on...
Browser
Browser