NSU M. Pharm.

AP Dissolution 1 Theory, concepts, importance

DISSOLUTION
THEORY AND CONCEPTS OF DISSOLUTION OF SOLIDS Definition of terms Disintegration Breakdown of tablet into granules and aggregates. Dissolution Process of being dissolved and going into solution. Diffusion Movement of molecules/ions from higher concentration to lower concentration. Drug release Liberation of drug from a dosage form and becoming available for absorption. This term is mainly used for modified release ( MR ) drug products. Dissolution is the process by which a solid substance enters the solvent phase to yield a solution. In other words, the transfer of molecules or ions from a solid state into solution is known as dissolution.

NSU M. Pharm. AP Dissolution 1 Theory, concepts, importance

Dissolution mechanism

Step 1: Solute molecules are liberated from the solid phase and get dissolved in the adjacent solvent layer to form a saturated solution. This interfacial step is virtually instantaneous.

Step 2: The solute molecules are migrated from the saturated solution through the stagnant boundary layers surrounding the solid phase to the bulk of the solution under the influence of diffusion or convection. This is the slower and rate limiting step of the dissolution process.

NSU M. Pharm. AP Dissolution 1 Theory, concepts, importance

Rate of dissolution - Noyes-Whitney equation Mass transfer must take place through the boundary layers ( stagnant liquid ) to form the solution. The rate of dissolution of a solid in a liquid has been described by NoyesWhitney equation. Dissolution rate can be expressed in terms of mass transfer occurring per unit time.

NSU M. Pharm. AP Dissolution 1 Theory, concepts, importance

Dissolution rate can be also be expressed in terms of concentration change occurring per unit time. M = mass of solute dissolved in time t dM / dt = rate of dissolution in terms of mass transfer per unit time ( mass / time ) dC / dt = rate of dissolution in terms of concentration change per unit time ( concentration / time ) D = diffusion coefficient of the solute in the boundary layer A = effective surface area of the exposed solid h = thickness of the stagnant boundary layer Cs = solubility of the solute ( saturation concentration ) Ct = concentration of the solute in bulk phase at time t V = volume of dissolution medium

NSU M. Pharm. AP Dissolution 1 Theory, concepts, importance

If Ct << Cs , then Cs Ct can be written as Cs This condition is considered as 'sink condition'. The Noyes-Whitney equation describes diffusion controlled dissolution process. The sink condition exists in vivo and must also be maintained while performing in vitro dissolution testing. Under strictly controlled conditions of temperature, agitation etc, D, Cs and h can be considered as constants. Thus, the mass transfer equation becomes:

NSU M. Pharm. AP Dissolution 1 Theory, concepts, importance

The term k is known as 'intrinsic dissolution rate' and denotes the amount of substance dissolved per unit area per unit time. The unit of k is mass / area / time ( mg.cm2.min1 ). The working formula from for determining IDR is M / t = k . A where M = mass of solid dissolved at time t. So, M = k . A . t To determine IDR, dissolution of solid drug is performed keeping surface area constant. Temperature, volume of fluid and its pH, and stirring rate should also be specified. This is a equation of a straight line.

NSU M. Pharm. AP Dissolution 1 Theory, concepts, importance

To determine IDR, amount of drug dissolved ( M ) is plotted against time ( t ) and k is obtained by dividing the slope by the exposed surface area. IDR is associated with zero order process. IDR is used to compare the dissolution rates of different solid materials like drugs and excipients. While mentioning IDR value of a substance ( drug or excipient ), the experimental conditions must also be stated.

NSU M. Pharm. AP Dissolution 1 Theory, concepts, importance

Kaplans suggestion regarding IDR of drug substances: IDR ( mg.cm2.min1 ) >1 0.1 - 1 < 0.1 Dissolution rate limited absorption problem not likely to occur more investigation required before making any comment likely to occur

IDR of some common diluents ( fillers ): Intrinsic dissolution rate ( IDR ) of two fillers: Filler Anhydrous lactose Medium Purified water IDR ( at 37C ) 21.9 mg.cm2.min1 12.4 mg.cm2.min1

Lactose monohydrate Purified water

NSU M. Pharm. AP Dissolution 1 Theory, concepts, importance

Importance of dissolution Dosage form dissolution absorption bioavailability drug action Absorption and subsequent bioavailability are affected by both rate and extent of drug dissolution.

ADME and action of a drug will not occur unless dissolution of the drug in biological fluids takes place. Thus, all these processes are possible only when the drug is in solution.

NSU M. Pharm. AP Dissolution 1 Theory, concepts, importance

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Dissolution and release of drugs from dosage forms is important for ensuring bioavailability that is adequate and effective concentration of drug in the blood. The rate and extent of drug dissolution from dosage form can be influenced by the following factors:

Bioavailability problems of dosage forms can occur due to the effects of these factors on the rate and extent of drug dissolution. Thus, these factors must be optimized during product development.

NSU M. Pharm. AP Dissolution 1 Theory, concepts, importance

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