The component that determines the phase of the solution is termed the solvent ; it usually but not necessarily constitutes the largest proportion of the system. The other component s are termed solute s and these are dispersed as molecules or ions throughout the solvent, i.
The transfer of molecules or ions from a solid state into solution is known as dissolution. Fundamentally, this process is controlled by the relative affinity between the molecules of the solid substance and those of the solvent.
The extent to which the dissolution proceeds under a given set of experimental conditions is referred to as the solubility of the solute in the solvent. The solubility of a substance is the amount of it that passes into solution when equilibrium is established between the solute in solution and the excess undissolved substance. The solution that is obtained under these conditions is said to be saturated. A solution with a concentration less than that at equilibrium is said to be subsaturated.
Solutions with a concentration greater than equilibrium can be obtained in certain conditions; these are known as supersaturated solutions. Since the above definitions are general ones, they may be applied to all types of solution involving any of the three states of matter gas, liquid, solid dissolved in any of the three states of matter, i.
However, when the two components forming a solution are either both gases or both liquids, then it is more usual to talk in terms of miscibility rather than solubility. Other than the name, all principles are the same. One point to emphasize at this stage is that the rate of solution dissolution rate and amount which can be dissolved solubility are not the same and are not necessarily related. In practice, high drug solubility is usually associated with a high dissolution rate, but there are exceptions; an example is the commonly used film-coating material hydroxypropyl methylcellulose HPMC which is very water soluble yet takes many hours to hydrate and dissolve.
The majority of drugs and excipients are crystalline solids. Liquid, semi-solid and amorphous solid drugs and excipients do exist but these are in the minority. For now, we will restrict our discussion to dissolution of crystalline solids into liquid solvents. Also, to simplify the discussion, it will be assumed that the drug is molecular in nature. The same discussion applies to ionic drugs. Again, to avoid undue repetition in the explanations that follow, it can be assumed that most solid crystalline materials, whether drugs or excipients, will dissolve in a similar manner.
The dissolution of a solid in a liquid may be regarded as being composed of two consecutive stages. First is an interfacial reaction that results in the liberation of solute molecules from the solid phase to the liquid phase. This involves a phase change so that molecules of solid become molecules of solute in the solvent in which the crystal is dissolving.
After this, the solute molecules must migrate through the boundary layers surrounding the crystal to the bulk of solution. These stages, and the associated solution concentration changes, are illustrated in Figure 2. Dissolution involves the replacement of crystal molecules by solvent molecules.
This is illustrated in Figure 2. The process of the removal of drug molecules from a solid, and their replacement by solvent molecules, is determined by the relative affinity of the various molecules involved. On leaving the solid surface, the drug molecule must become incorporated in the liquid phase, i. The process of dissolution may be considered, therefore, to involve the relocation of solute molecules from an environment where they are surrounded by other identical molecules, with which they form intermolecular attractions, into a cavity in a liquid where they are surrounded by non-identical molecules, with which they may interact to different degrees.
Boundary layers are static or slow-moving layers of liquid that surround all solid surfaces that are surrounded by liquid discussed further later in this chapter and in Chapter 6.
Mass transfer takes place more slowly usually by diffusion; Chapter 3 through these static or slow-moving layers that inhibit the movement of solute molecules from the surface of the solid to the bulk of the solution.
The solution in contact with the solid will be saturated because it is in direct contact with undissolved solid. During diffusion, the concentration of the solution in the boundary layers changes from being saturated C S at the crystal surface to being equal to that of the bulk of the solution C at its outermost limit, as shown in Figure 2. The free energy G is a measure of the energy available to the system to perform work.
Its value decreases during a spontaneously occurring process until an equilibrium position is reached when no more energy can be made available, i. In most cases heat is absorbed when dissolution occurs and the process is usually defined as an endothermic one. In some systems, where marked affinity between solute and solvent occurs, the overall enthalpy change becomes negative so that heat is evolved and the process is an exothermic one.
Like any reaction that involves consecutive stages, the overall rate of dissolution will be dependent on which of these steps is the slowest the rate-determining or rate-limiting step. On the rare occasions when the release of the molecule from the solid into solution is slow and the transport across the boundary layer to the bulk solution is faster, dissolution is said to be interfacially controlled.
The energy difference between the two concentration states provides the driving force for the diffusion. If C 2 is less than saturated, the molecules will move from the solid to the bulk as during dissolution.
If the concentration of the bulk C 2 is greater than this, the solution is referred to as supersaturated and movement of solid molecules will be in the direction of bulk solution to surface as occurs during crystallization. An equation known as the Noyes—Whitney equation was developed to define the dissolution from a single spherical particle.
This equation has found great usefulness in the estimation or prediction of the dissolution rate of pharmaceutical particles. This relationship is shown in Equation 2. The constant k 1 is known as the diffusion coefficient.
If the volume of the solvent is large, or solute is removed from the bulk of the dissolution medium by some process at a faster rate than it passes into solution, then C remains close to zero and the term C S — C in Equation 2. The concentration of the solute The temperature of the system The polarity of the solvent The polarity of the solute The pressure of the system.
Commonly asked questions on solubility and dissolution are as follows. Both solubility and dissolution rate are two different phenomena. The solubility of the sample in a solvent may be poor, but its dissolution rate might be high. A solute, on the other hand, can be very soluble but take a long time to reach its final saturation concentration.
The dissolution can determine the rate of release and the extent of absorption of the dosage forms, which is a major advantage of dissolution.
A mechanism by which a solute in a liquid, solid, or gaseous phase dissolves in a solvent to form a solution is known as dissolution. You may also like this. Difference between Dissolution and Dissociation. Difference between Dissociation and Ionization. Difference between Dissolution and Disintegration. Difference between Dissolution and Diffusion. At times, dissolution might occur due to a chemical reaction and not due to the pure solubility of the solute.
This should not be confused over solubility. When a solute is purely soluble, one should be able to obtain the solute back again after the evaporation of the solvent. Dissolution is the process where a solute dissolves in a solvent to form a solution. Therefore, this has a kinetic effect. Dissolution can occur at various rates and sometimes for a solute to completely dissolve in a solvent it might require quite a length of time.
During the process of dissolution, the structural integrity of the solute is broken down into individual components, molecules or atoms, and the outcome of dissolution is referred to as solubility. Dissolution too is governed by similar physical principles as for solubility, but dissolution itself is a kinetic process. The rate of dissolution depends on various factors; mechanical mixing, nature of solvent and solute, mass of dissolved material, temperature etc.
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