Dissolution is a process in which a solid substance solubilizes in a given solvent i.e. mass transfer from the solid surface to the liquid phase.
Dissolution is the rate determining step for hydrophobic,
poorly aqueous soluble drugs.
Why dissolution studies?
To show that the release of drug from the tablet is close to 100%.
To show that the rate of drug release is uniform batch to batch.
And to show that release is equivalent to those batches proven to be bioavailable and clinically effective.
Apparatus Classification in USP:
Apparatus 1 (rotating basket)
Apparatus 2 (paddle assembly)
Apparatus 3 (reciprocating cylinder)
Apparatus 4 (flow-through cell)
Apparatus 5 (paddle over disk)
Apparatus 6 (cylinder)
Apparatus 7 (reciprocating holder)
A drug product is considered rapidly dissolving when;
no less than 85% of the labeled amount of the drug substance dissolves within 30 minutes, using USP Apparatus I at 100 rpm (or Apparatus II at 50 rpm) in a volume of 900 ml or less in each of the following media:
1 N HCl or Simulated Gastric Fluid USP without enzymes;
a pH 5 buffer; and
a pH 8 buffer.
Biopharmaceutical Classification System;
Class I:
High solubility—High permeability
Class II:
Low solubility—High permeability
Class III:
High solubility—Low permeability
Class IV:
Low solubility—Low permeability
Why Qualification & Validation of the Apparatus?
-To maintain “quality by design”.
-Physical & chemical calibrations—for geometrical & dimensional accuracy & precision.
-Vibration or undesired agitation to be avoided.
-Temperature, rotation speed/flow rate, volume, sampling probe, procedures, etc. need to be monitored periodically.
Use of USP calibrator tablets for App. 1 & 2 (to be performed not less than twice a year)
Solubility of solid in dissolution medium;
Temperature of dissolution medium.
pH of the medium.
Solubility of the drug in dissolution medium.
Presence of co-solvents.
Dissolution rate constant
Depend upon;
Thickness of boundary layer
Degree of agitation
Speed of stirring
Shape, size & position of stirrer
volume of dissolution medium
Shape & size of container
Viscosity of dissolution medium
Dissolution Acceptance Criteria in case of Failure;
