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DISSOLUTIONMADE BY : UDAY JOSHI

DISSOLUTION

Drug in blood or other fluids & tissuesDeaggregationDisintegration2DISSOLUTIONDissolution refers to a process by which a solid phase (e.g. a tablet or capsule) goes into solution phase such as water. It 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.3DISSOLUTIONRate of dissolution is the amount of drug substance that goes in solution per unit time under standardized conditions of liquid/solid interface, temperature and solvent composition.Usually drugs in solution could only undergo ADME and hence exert therapeutic actionDissolution is often the rate limiting step in the absorption of the drugs with low solubility4OFFICIAL METHODS OF DISSOLUTION5DISSOLUTION APPARATUSESType I: Basket typeType II: Paddle typeType III: Reciprocating cylinder typeType IV: Flow through cell typeType V : Paddle over disk for transdermal systemType VI: Cylinder type apparatusType VII: Reciprocating holder used for variety of solid dosage forms.6

Apparatus 1 - BasketApplicationsIR dosage forms of soluble drugsCapsulesBeadsDelayed release / entericcoated dosage formsFloating dosage formsSurfactants in mediapH change by media addition or replacement

Standard parameters900/1000 ml1, 2, 4 liter vessels 50-100 rpm

77Apparatus 1 - BasketAdvantagesBroad experience(more than 200 monographs)Easy to operateRobustCan be easily automated which is important for routine investigations

DisadvantagesHydrodynamic dead zone under the basket, degassing is particularly importantFormulation may clog the screenSmall disintegrated particles fall out

88Apparatus 1 - Basket

99Apparatus 2 - PaddleMethod of first choice !!!Useful forIR dosage forms of soluble drugsTabletsCapsulesBeadsDelayed release / entericcoated dosage formsStandard parameters900/1000 ml volume50-75 rpm

1010Sinker typesA small loose piece of nonreactive material such as not more than a few turns of wire helix may be attached to dosage units that would otherwise float . other validated sinker devices may be used

1111Apparatus 2 - PaddleAdvantagesEasy to useRobustCan be easily adapted to apparatus 5Can be easily automated which is important for routine investigations

1212Apparatus 2 - PaddleDisadvantagespH/media change is often difficultPositioning of the dosage form is important. Hydrodynamics vary with site of the dosage form in the vessel (sticking, floating) and therefore may significantly affect drug dissolutionCone formationSinkers for floating dosage forms1313Coning

Apparatus 2 - Paddle

1515Apparatus 3 Reciprocating cylinderUseful forTabletsBeadsModified release formulations

Standard volume200-250 ml per station

Vessels: Cylindrical flat-bottomed glass

Glass reciprocating cylinders: Inert fittings and screens at the top and bottom of the cylinders

1616Apparatus 3 Reciprocating cylinderAdvantagesMedia change fully automatedEase of samplingSuitable for QC testing of productsSmall media volumes suitable for generating pH profilesHydrodynamics more similar to those in the gastrointestinal tract

DisadvantagesSmall volume (max. 250 ml)Little experienceSurfactants cause foaming

1717Apparatus 3 Reciprocating cylinder

1818Useful forLow solubility drugsMicroparticlesImplantsSuppositoriesControlled release formulations

VariationsOpen systemClosed system

Apparatus 4 Flow-Through Cell1919Apparatus 4 Flow-Through CellAdvantagesUnlimited fluid supply makes it ideal for testing poorly soluble drugsGentle hydrodynamic conditions and possibility of varying hydrodynamics during the testAllows for rapid media changeContinuous sampling

DisadvantagesDeaeration necessaryHigh volumes of media

2020Apparatus 4 Flow-Through Cell

2121Cell types

Apparatus 5 Paddle over diskUseful forTransdermal patches

Standard volume900 ml

2323Apparatus 5 Paddle over diskAdvantagesStandard equipment (paddle) can be used, only add a stainless steel disk assembly

DisadvantagesDisk assembly restricts patch size

2424Apparatus 6 Rotating cylinder USP apparatus 7 Reciprocating holderUses vessel assembly from Apparatus 1 but replaces basket and shaft with a stainless steel cylinder stirring element Temperature: 32CDosage unit is placed on the cylinder with release side out Drug products: Reservoir transdermal patches

2525USP apparatus 7 Reciprocating holder

Similar to Apparatus 3 but with different dimensionsTemperature: 32C (for transdermal dosage forms)Various devices to hold transdermal patches, tablets, capsules, implantsSpeed: 20-50 dpmReciprocation through 2cm

2626SummaryImmediate release dosage forms: Apparatus 1 or 2 (preferably 2)Controlled release dosage forms: Apparatus 1 or 2 using different media for QC Apparatus 3 or 4 for R&D purposesBeside the selection of an adequate dissolution apparatus, adequate test conditions are crucial for all purposes !2727THANK YOU