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Buffered Isotonic Solutions, Measurements of Tonicity, Calculations and Methods of Adjusting Isotonicity

Pharmaceutical solutions used in contact with delicate membranes of the body need to have an approximately equal osmotic pressure as the body itself.

Buffered isotonic solutions

Additionally, to pH adjustment, pharmaceutical solutions used in contact with delicate membranes of the body need to have an approximately equal osmotic pressure as the body itself. From a region of lower solute concentration to a region of higher solute concentration, molecules of a solution can pass through a semipermeable membrane, but not its molecules.

Think about two semipermeable membranes where the concentration of solute in the two solutions is different. From regions with low solute concentrations, solvent molecules move to regions with high concentrations of solutes until equilibrium is achieved. During this process, osmotic pressure must be applied to maintain the movement. Osmotic pressure is an expression of a solution's state that is influenced by its ionization, aggregation, and particle count. An osmotic pressure equivalent to 0.9% (w / v) sodium chloride is found in body fluids (blood and lacrimal fluid). In this case, 0.9% (w/v) sodium chloride solution is iso-osmotically equivalent to physiological fluids. Iso-Osmotics and isotonic are terms that are interchangeable in medicine. Physiological solutions with osmotic pressures lower than body fluids or sodium chloride concentrations of 0.9% (w/v) are termed hypotonic, while solutions with osmotic pressures higher than body fluids are called hypertonic.

Osmolality and osmolarity: Concentrations of solutions can be expressed as osmolality or osmolarity.

Osmolality: An osmolal concentration is measured by osmolality. For solutions containing over 1 osmol of solute per kilogram of water, the osmolality concentration is 1, and for solutions with over N osmol per kilogram, the osmolality concentration is N. Solvent-solvent solutions represent the weight-to-weight relationship between solvents and solutes.

Osmolarity: The osmolality of substances is a measure of their osmolarity. Osmolality in a solution is measured as one when the total solute concentration per litre is one, and as n when there is n total solute concentration per litre of solution. The relationship between solute and final solution is based on weight to volume, and it is equivalent to the concept of molecular solutions.

Measurement in tonicity, calculations and methods for adjusting tonicity

The tonicity of a drug solution can be adjusted in two methods: Class I methods, in which sodium chloride or some other substance is dissolved into the solution to lower the freezing point and make it isotonic with body fluids. The cryoscopy method is included in this method, as well as the chloride equivalent method. In order to form a solution that is isotonic, sufficient water must be added to the drug. In the final step, the preparation is diluted with buffered isotonic dilution solution to make it up to its final volume. Methods like the White–Vincent and Sprowls method are among them.

Class I method

Cryoscopy method

By considering the colliding properties of solutions, an isotonic solution can be created. Osmotic pressure is not the only collaborative property. Besides reducing the vapour pressure, cooperative properties include raising the boiling point and reducing the freezing point. Colder temperatures lead to a lower freezing point, which is a collative property that is most helpful for adjusting tonicity. Lacrimal fluid and human blood have freezing points of -0.52 °C. As a result, this temperature is equivalent to the freezing point of sodium chloride solution with a 0.90% (w/v) concentration. Lacrimal fluids and blood are considered isotonic fluids. With a freezing point depression of 0.58°C, 1.5% sodium chloride (ΔTf1%) has a freezing point of 1.5% (w/v). The method involves adding a tonicity adjuster (e.g., sodium chloride) to drug solution in order to lower the final freezing point to 0.52°C, that is, the freezing point of blood or serum.

Sodium chloride equivalent method

Sodium chloride equivalents, also known as E-values or tonicity equivalents, are used to indicate the potency or strength of a drug. This is simply the amount of sodium chloride equivalent to a gram of a drug that has a similar osmotic effect (i.e., is equivalent to) the sodium chloride.

Deviation of E-value: It is a collective property, so freezing point depression is dependent on both particle numbers, as well as particle dissociation and association.

Thus, the equation

∆Tf = KfC is Replaceable with

∆Tf = LisoC


A depression at freezing point is known as ΔT,

This constant measures the freezing point depression, Kf

The concentration is c.

The vant Hoff factor, i, determines Liso, while the vant Hoff factor, k, determines Kf.

Liso= ∆Tf / C

Class II methods

White – Vincent method

For Class II tonicity calculations, the drugs are mixed with water to create an isotonic solution, and then they are diluted with an isotonic diluting agent until their concentration is the final concentration. In White and Vincent's approach, such calculations are simplified.

The weight w of the drug is multiplied by the sodium chloride equivalent E to prepare 30 mL of 1% (w/v) procaine hydrochloride solution isotonic with body fluid (=0.3 g).

0.3 grams of procaine hydrochloride is equivalent to this amount of sodium chloride

= weight of the drug (g) × E of drug                           (1)

= 0.3 × 0.21

= 0.063 g

The sodium chloride formula is known to yield an isotonic solution when it is dissolved in approximately 100 mL of water. 0.2 g of procaine hydrochloride is equivalent to 0.063 g of sodium chloride, so by solving the following proportion we can obtain volume V:

0.9 g / 100 ml

= 0.063 g / V

V = 0.063 X 100 / 0.9

= 7.0 ml                                   (2)

Eq.(2), therefore, can be expressed as

V = w × E × 111.1

Isotonic solutions are formulated by combining a volume measured in millilitres and a weight expressed in grams or equivalent amount of sodium chloride expressed in grams. A volume of isotonic solution in millilitres is equal to one gram of sodium chloride dissolved in water.

Diluting solutions containing 0.9% NaCl are both isotonic and contain isotonic-buffered solutions.

Sprowls method

Sprowls developed a simplified version of the White-Vincent method. For this experiment, 0.3 g of a 1% solution was chosen for use because it is the amount for one fluid ounce. For example, using White and Vincent's expression (V = w × E × 111.1) to calculate the volume V of an isotonic solution formulated as an ophthalmic and parenteral solution using 0.3g of a drug dissolved in sufficient water is possible. Diluted isotonic solutions can be reached by adding the desired form of isotonic solution to a particular volume of isotonic solution.
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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