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Singh, Singh, and Singh: Solubility: An overview


The term 'solubility' is characterized as maximum amount of solute that can be dissolved in a given measure of solvent. Quantitatively it is characterized as the concentration of the solute in a soaked solution at a specific temperature. solubility might be considered as the extemporaneous collaboration of two or more uniform molecular dispersion.1 The substance to be dissolved is called as solute and the dissolving liquid in which the solute dissolved is called as solvent, which composed form a solution and process of dissolving solute into solvent known as hydration or solution if the solvent is water. Solubility is kind of the property of a liquid, solid, and gaseous chemical substance called solute to dissolve in a liquid, solid, and gaseous solvent to form a homogeneous solution of the solute in the solvent.2, 3

The solubility of a substance essentially depends upon the solvent utilized and in addition on temperature and pressure. Solubility occurs under unique equilibrium, which implies that solvency comes about because of the concurrent and opposing processes of dissolution and phase joining (e.g., precipitation of solids).Below certain conditions equilibrium solubility might be surpassed to give a supposed supersaturated solution which is called as metastable.3 Solubility isn't to be mistaken for the capacity to dissolved or on the other hand liquefy a substance, since these processes may happen not only because of dissolution however due to chemical reaction. For example zinc is insoluble in hydrochloric acid, be that as it may, dissolves in it by chemically reacting into zinc chloride and hydrogen, where zinc chloride is soluble in hydrochloric acid. Solubility does not also depend on any kind of particle size or other kinetic factors which are given enough time, even big particles will finally dissolve. Saturated solutions of ionic mixes of generally low solubility are occasionally described by solubility constant portrayed by dissolvability constants.

The Flory-Huggins solution hypothesis is a hypothetical model depicting the solubility of polymers. The Hansen Solubility Parameters and the Hildebrand solvency parameters are empirical strategies for the expectation of solubility. It is also possible to predict solubility from other physical constants for example, the enthalpy of combination.4

Solubility Expressions

The British Pharmacopeia and United States Pharmacopeia expressions shown in Table 1.

Table 1

Solubility definition in the United States Pharmacopeia5

Description forms (solubility definition)

Parts of solvent required for one part of solute

Solubility Range (mg/mL)

Solubility Assigned (mg/mL)

Very soluble




Freely Soluble

1 to 10




10 to 30



Sparingly Soluble

30 to 100



Slightly Soluble

100 to 1000



Very slightly Soluble

1000 to 10,000



Practically insoluble




Table 2

BCS Classification6




Absorption Pattern

Rate limiting step in absorption




Well absorb

Gastric emptying














Poorly Absorb

Case by case

Mechanisms of Solute Solvent Interactions

Solutions are homogeneous liquid phases comprising of solute and solvent in factor proportions. In solution the solute is dispersed consistently all through the solvent. Regularly, the component which is in excess is known as the solvent and the minor component(s) is the solute. Solvent might be a pure liquid or it might be a blend of at least two liquids. These empirical finding are summarized in statement “Like dissolve like” as follow are

If solute and solvent intermolecular forces are:7, 8

Similar… the pair will be soluble.

  1. Polar dissolves polar

  2. Non-polar dissolves non-polar

  3. Dissimilar… insoluble.

Substances dissolve when

Solvent-solute attraction > solvent-solvent attraction, and > solute-solute attraction.

Miscible liquids dissolve in all proportions.

E.g. ethanol and water (both H-bonded polar liquids.

Immiscible liquids form distinct separate phases.

E.g. gasoline (non-polar and water (polar).

Table 3

Solubility of different solvent



Solubility (g/100g H2O @20°C)




London Force Increasing
















Water solubility decreases as alcohols grow larger:

  1. Solute-solute attraction grows.

  2. Solute-solvent attraction stays ≈ constant.

Polar solvents

In the polar solvent solubility of drug because in large measure to the polarity of the solvent that dipole moment. Water mixed in all proportions with alcohol and dissolve sugar and other polyhydroxy compounds. Other example water dissolves phenols, alcohols, aldehyde, ketones, amines, oxygen and nitrogen containing compound which can be bond with water.

Non-polar solvents

These are those solvents or liquids which are differs from the polar solvents. These are unable to reduce the attraction between the strong ions and electrolyte of weak due to the solvent dielectric constant. Non-polar compounds are dissolve in polar solutes with internal pressures throughout induced dipole interaction. The solute molecules are kept solution due to weak Vander Waals London type of forces. Example Oils and fats dissolve in carbon tetrachloride, mineral oil, alkaloid, benzene, and fatty acid.

Semipolar solvents

Semipolar solvents are ketones and alcohol can induce certain degree of polarity in non-polar substance. Likewise benzene is readily polarizable becomes soluble in alcohol.

Table 4

Polarity of some solutes and solvents

Decreasing Polarity

Dielectric constant of solvent



Decreasing Water Solubility


Inorganic or organic salts



Tannins and sugar



Caster oil

Ethyl or Methyl alcohols


Volatile oil, weak electrolyte, alkaloids, phenols, including barbiturates and resins

Ketones, aldehyde.ethers, esters,


Fixed oils, fats

Hexane, Benzene

Ideal Solubility Parameters

The different types of ideal solubility parameters following are 9

Strength and nature of solute solvent attraction

This is also called as intermolecular interaction. The fascination of the solvent for solute particles cement powers is contrary to the fascination of solute atoms to themselves durable powers, the activity can spoke to by utilizing harmony condition follow as


Solute + Solvent ⇄ solution Crystallization

Polarities of the solute and solvent

The solvent contains polar particles (e.g., water), polar solutes will be more pulled in to the solvent than will nonpolar solutes. Nonpolar solutes will have some appreciation for polar particles, by means of dipole– prompted dipole activities, yet the extents of these attractions will be substantially littler. Hence, polar solutes will for the most part be more solvent in polar solvents.

The thermodynamics of the dissolution. According the Gibbs free energy equation, ΔG = ΔH − TΔS, where ΔG is the change in Gibbs free energy (energy to do work), ΔH is the change in enthalpy, and ΔS is the change in entropy. Increases in enthalpy are thermodynamically unfavorable when taken alone, whereas increases in entropy are favorable when taken alone.

Overall, to be thermodynamically favorable, a negative ΔG is required.


Endothermic processes are reactions in which heat is absorbed (ΔH > 0). Exothermic processes are those in which heat is released (ΔH < 0). If the ambient temperature is relatively high, exothermic dissolution processes will be inhibited, while endothermic dissolution processes will be improved. Temperature influences solubility and is additionally thermodynamically related. The effect of temperature on dissolvability depends whether the particular disintegration n measure is endothermic or exothermic in nature and the incorporating biological conditions. Endothermic procedures are responses in which heat is consumed (ΔH > 0). Exothermic procedures are those in which heat is discharged (ΔH < 0). In the event that the encompassing temperature is generally high, exothermic dissolution procedures will be hindered, while endothermic dissolution procedures will be improved along these lines, high surrounding temperatures will expand the solubility of solutes with endothermic disintegration forms, however, diminish the solubility of those with exothermic processes.

Ionization of solute and solvent, and pH of the solvent

The pH of the solvent can significantly affect the solubility of ionizable solutes. Acidic drugs are fewer soluble in acid solutions because more of the drug tends to be in the unionized form, which is less able to interact with the solvent (water) than the ionized form.

Quantitative Approach to the Factors Influencing Solubility of Quantitative Approach to the Factors Influencing Solubility of Drugs


For gaseous solutes, an expansion in pressure rises solubility and a decline in pressure decline the Solubility. For solids and liquid solutes, changes in pressure have for all intents and practically no impact on solubility.10


Temperature will affect solubility. If the process of solution absorbs energy then the temperature is raised the solubility will be raised. If the process of solution releases energy then the solubility will decline with raised temperature. Commonly, a raised in the temperature of the solution rises the solubility of a solid solute. A few solid solutes are few soluble in warm solutions. For all gases solubility declines as the temperature of the solution rises.11

Molecular size

The bigger the molecule or the greater its molecular weight the less soluble the substance. Greater molecules are harder to edge with solvent molecules in direction to solvate the substance. In the case of organic compounds the quantity of carbon branching will rise the solubility subsequently more branching will decrease the size and volume of the molecule and make it easier to solvate the molecules with solvent.12

Particle size

Particle size effect on solubility as article size decreases, the surface area to volume ratio increases. The effect of particle size on solubility can be described by,13

Figure 0


S0- is the solubility of infinitely large particles

S- Is the solubility of fine particles?

V- Is molar volume

γ-is the surface tension of the solid

r- is the radius of the fine particle

T- is the absolute temperature

R- is the gas constant

Nature of solute and solvent

The idea of solute and solvent relies upon convergence of solute in explicit amount of solvent at explicit temperature. Example: at room temperature in 100gm of water only 1gm of lead (II) chloride can be dissolved while 200 grams of zinc chloride can be dissolved.14


A solid has an inflexible shape and a clear shape. The shape or habit for a crystal of a given substance may vary however the points between the faces are constantly consistent. A crystal is comprised of particles, particles, or particles in a normal geometric game plan or grid continually rehashed in three measurements. This rehashing design is known as the unit cell. The limit with respect to a substance to take shape in more than one crystalline shape is polymorphism. It is conceivable that all crystal can solidify in diverse structures or polymorphs. On the off chance that the change starting with one polymorph then onto the next is reversible, the procedure is called enantiotropy. In the event that the systems is monotropic, there is a change point over the liquefying purposes of both polymorphs. The two polymorphs can't be changed over from each other without experiencing a phase transition.13


Polarity of the solute and solvent molecules will distress the solubility. Commonly non-polar solute molecules will dissolve in non-polar solvents and polar solute molecules will dissolve in polar solvents. The polar solute atoms have a positive or a negative end to the particle. On the off chance that the dissolvable atom is additionally polar, at that point positive closures of dissolvable particles will pull in negative finishes of solute atoms. This is a sort of intermolecular power known as dipole-dipole connection. All particles likewise have a kind of intermolecular power a lot more fragile than different powers called London Dispersion powers where the positive cores of the iotas of the solute particle will pull in the negative electrons of the molecules. This gives the non-polar solvent a chance to solvate the solute molecules.11

Diffusion Principles in Biological Systems

Diffusion is the net inactive development of particles (iotas, particles or atoms) from a region where they are in higher fixation to zones of lower concentration.

It proceeds until the point that the concentration of substances is uniform all through.15

Table 5

Some major examples of diffusion in biology

Gas exchange at the alveoli

Oxygen from air to blood, carbon dioxide from blood to air


Diffusion of water through a semipermeable membrane

Transfer of transmitter substance

Acetylcholine from presynaptic to postsynaptic membrane at a synapse.

Gas exchange for respiration

Oxygen from blood to tissue cells, carbon dioxide in opposite direction

Facilitated diffusion

This is the development of particular molecules down a concentration gradient, going through the layer by means of a particular bearer protein. In this way, rather like enzymes, every bearer has its own shape and just permits one molecules (or one group of firmly related molecules to pass-through. Determination is by size; shape; charge. Regular molecules entering/leaving cells along these lines incorporate glucose and amino-acids. On the off chance that the molecules is changed on entering the cell

(Glucose + ATP → glucose phosphate + ADP), at that point the concentration gradient of glucose will be kept high, and there will a steady one-way activity.15


Osmosis is an exceptional case of diffusion. It is the diffusion of water through a mostly penetrable membrane from a more dilute solution for a more concentrated solution – down the water potential gradient) Note: diffusion and osmosis are both passive, i.e. energy from ATP isn't utilized. A partially permeable membrane is an obstruction that allows the passage a few substances however not others; it permits the entry of the solvent molecules yet not a portion of the bigger solute molecules. Cell membranes are depicted as specifically permeable since not exclusively do they permit the passage of water yet in addition permit the section of specific solutes. The presence of specific solutes stimulates the film to open particular channels or trigger active transport mechanisms to permit the section of those across the membrane.

Some major examples of osmosis

  1. Absorption of water by plant roots

  2. Re-absorption of water by the proximal and distal convoluted tubules of the nephron

  3. Re-absorption of tissue fluid into the venule ends of the blood capillaries

  4. Absorption of water by the alimentary canal — stomach, small intestine and the colon.

Active transport

Active transport is the energy requesting transfer of a substance across a cell membrane against its concentration gradient, i.e. lower concentration to higher concentration. Extraordinary proteins inside the cell membrane go about as particular protein 'transporters'. The energy for active transport originates from ATP produced by respiration (in mitochondria).15


This is the development of substantial molecules (bacteria or particles, or other organisms) over the cell membrane. It includes the combination of vesicles (containing the target/victim)) with the cell membrane e.g. bacteria entering macrophages. Substances bound for secretion are packaged in the Golgi body first.

Pinocytosis ('cell drinking') This is the take-up of extensive molecules (DNA, protein) from solution, by a type of endocytosis – the vesicles formed are minute and short-lived.

Phagocytosis ('cell eating') This is the take-up of strong particles by a cell e.g. One-celled critter encouraging, phagocytes engulfing bacteria.15


Solubility of the medication is the main factor that controls the preparation of the medication just as remedial viability of the medication subsequently the most basic factor in the formulation of drug advancement. The solubility issue of numerous medications the bioavailability of them gets influenced so reduced this problem various solvents or parameters are used to increase the solubility of poorly soluble drugs. For diffusion based biological principle express that it is a significant passage by which numerous drug are entering or disposing of and is a premise of many drug delivery systems.

Source of Funding


Disclosure Statement 

There are no conflicts of interest.


The authors acknowledge the chairman of Mr. Anil Chopra, Vice Chairperson Ms. Sangeeta Chopra & Pro-Chairman Mr. Prince Chopra, St. Soldier Group of Educational Society, Jalandhar for providing the necessary facilities to complete this review work.



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