A REVIEW : SELECTION OF DISSOLUTION MEDIA

 

 

ABOUT AUTHOR:
Mr. Ripal Mistry
M.pharm, Indubhai Patel College Of Pharmacy & Research Center,
Dharmaj
Rx.ripalmistry@gmail.com

DEFINATION:

  • “Dissolution is the process by which a solid substance enters the solvent phase to yield a solution i.e. mass transfer from solid surface to liquid phase”.
  • Dissolution Rate: It is the amount of drug substance that goes in solution per unit time under standardized conditions of temperature and solvent composition.

IMPORTANCE:

  • Dissolution testing is mainly used to confirm product quality and batch-to-batch consistency.
  • Dissolution testing finds application in bioavailability problems and bioequivalence studies.
  • In R&D department, comparing In vitro dissolution data with In vivo bioavailability,we would greatly facilitate product development.

Reference Id: PHARMATUTOR-ART-1971


Some of the steps involved in the absorption of drugs administered orally from solid dosage forms. GI,gastrointestinal.

HISTORY OF DISSOLUTION:

  • It all started in 1897 with the first reference to dissolution: Noyes and Whitney publish a paper on “The Rate of Solution of Solid Substances in Their Own Solution.” They suggested that the dissolution rate was controlled by a layer of saturated solution that forms instantly around a solid particle.
  • A few years later in 1900, Brunner and Tolloczko proved that dissolution rate depended on the chemical, physical structures of the solid, the surface area exposed to the medium, agitation speed, medium temperature and the overall design of the dissolution apparatus.
  • 1904-Nernst and Brunner modified the Noyes-Whitney equation by applying Fick’s law of diffusion. A relationship between the dissolution rate and the diffusion coefficient was established.

SELECTION OF DISSOLUTION MEDIA:

The selection of an appropriate dissolution medium is a fundamental stage of the dissolution test.

- It is more important that the test closely simulate the environment in the GI tract than necessarily produce sink condition.

- SINK CONDITION:
The dissolution rate may be given by Novey-Whitney equation.


Where, S : surface area
t:time
Cs – Ct : concentration gradient between the concentration of solute in the stagnantlayer

  • This is first order dissolution rate process, for which the driving force is concentration gradient.
  • This is true for in-vitro dissolution which is characterized by non-sink conditions.
  • The in-vivo dissolution is rapid as sink conditions are maintained by absorption of drug in systemic circulation i.e. Cb=0 and rate of dissolution is maximum.
  • Under sink conditions, if the volume and surface area of the solid are kept constant, then,

dW/dt = K

  • This represents that the dissolution rate is constant under sink conditions and follows zero order kinetics.


So, we have to maintain sink condition in in-vitro. This is can be achieved by,

i. Bathing the dissolving solid in fresh solvent from time to time
ii. Increasing the volume of dissolution fluid
iii. Removing the dissolved drug by patitioning it from the aqueous phase of the dissolution fluid into an organic phase placed either above or below the fluid, for example, hexane or chloroform
iv. Adding a water miscible solvent such as alcohol to the dissolution medium
v. By adding selected adsorbent to remove the dissolved drug.

  • A sink condition occurs when the drug that can be dissolved in the dissolution medium is 3 times greater than the amount of drug to be dissolved.
  • Cs/Cd≤3
  • Suppose we have product with label claim 200mg and say solubility is 1 mg/ml then oboviously 200 ml is sufficient for its solubility.If you maintan sink conditions with say 220ml or 230 ml ithink it practically difficult to work with or dissolutions with these small amounts of medium.Hence it is better to maintain 3:1 ration.

- A flow-through system and reservoir may be used to provide sink conditions by continually removing solvent and replacing it with fresh solvent .

- The dissolution characteristics of oral formulations should be evaluated over the physiologic pH range of 1.2 -6.8.


The pH of the stomach before and after meal.

  • From above  we can say than the main difference seen in the Stomach pH,this is due to the secreation of the gastric juice mainly HCl.
  • The Enteric coated tablet is tested using the basket or paddle apparatus initially containing 750 ml of 0.1N HCl. After two hours of exposure, a sample is removed for analysis, 250 ml of phosphate buffer is immediately added and the mixed contents of the dissolution vessel adjusted to a pH of 6.8±0.05.
  • For very poorly soluble compounds, aqueous solutions may contain a percentage of a surfactant (e.g., sodium lauryl sulfate, Tween 80, Cremophor, Triton, terigitol, cyclodextrin or Span 80) that is used to enhance drug solubility.
  • The need for surfactants and the concentrations used should be justified dued to it’s toxicity.
  • The surfactant is added to mimic the action of the Bile salts

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