A dissolution study of Ibuprofen in a flow-through-cell

302520reach saturation at start with neither of thedoses but sink condition was not establisheddespite this fact.% Upplöst15105050mg100mgWhen changing the cell diameter from 22.6mmto a smaller one, 12mm, the dissolutionincreased (fig. 6).0 50 100 150 200Tid (min)60Figure 4. Percentage dissolved ibuprofen, 50µm,in hydrochloric acid using the flow-through-cell,22.6mm cell and volume flow 8ml/min, two doses,50mg and 100mg.% Upplöst504030201012mm22.6mmThe smaller dose gave a higher dissolutionpercent (fig 4). The reason is that the massratio between drug dosage and glass beads ischanged when the dose is altered. When thesmaller dose was used the particles wherebetter separated resulting in a better wetting ofeach particle. However when comparing themass (mg) dissolved the larger drug dose gavea higher value (fig. 5).25201510500 50 100 150 200Tid (min)100 mgFigure 5. Mass dissolved ibuprofen, 50µm inhydrochloric acid using the flow-through-cell,22.6mm cell, volume flow 8ml/min, two doses,50mg and 100mg.This can be explained by the samplescontaining different amounts of fine particlesthat has a fast dissolution rate. They both hasthe same particle size, 50µm, though the largedose has in theory the double amount of fineparticles.Table 2. Std. and conc. at start of ibuprofen,50µm, in hydrochloric acid using the flowthrough-cell,22.6mm cell, volume flow 8ml/min,two doses, 50mg and 100mg.Dose Standarddeviation (mg/ml)Concentration(mg/ml) at start50mg 3.7 0.029100mg 1.3 0.02650 mg00 50 100 150 200Tid (min)Figure 6. Percentage dissolved ibuprofen, 50mg,50µm, in hydrochloric acid using the flowthrough-cell,volume flow 8ml/min, two celldiameters 12mm and 22.6mm.This is because a smaller diameter gives ahigher linear velocity (cm/min) of the medium.A faster flow past the drug particles gives athinner boundary layer and a faster dissolutionrate.Table 3. Std. and conc. at start of ibuprofen,50mg, 50µm, in hydrochloric acid using the flowthrough-cell,volume flow 8ml/min, cell diameters12mm and 22.6mm.Celldiameter(mm)Standarddeviation (mg/ml)Concentration(mg/ml) at start12 1.8 0.04922.6 3.7 0.029The test was working under non-sink conditionwhen using a smaller cell diameter which is adisadvantage. The standard deviation wassmaller when the small cell diameter was usedmeaning that a better reproducibility wasobtained using this.The linear velocity can also be changed byusing a different volumetric flow. Two volumeflows were used together with the large celldiameter, 22.6mm.The best reproducibility was obtained with thedose of 100mg. The concentration did not

Sink condition is more difficult to establish ifcetrimide is added and a higher standarddeviation is obtained.ConclusionsThe flow-through cell was studied at differentoperating conditions which resulted indifferent results in the following way:• A smaller particle size gave a higherdissolution rate• With a dose of 50mg a higher percentdissolved was obtained compared to adose of 100mg. However, a largermass (mg) was dissolved when thedose of 100mg was used• When using a cell diameter of 12mminstead of a cell diameter of 22.6mmthe dissolution rate increased.• A larger dissolution rate was obtainedwhen the flow of the medium wasincreased• By including a surfactant in themedium a drastic increase of thedissolution rate was obtained.dissolution apparatus, International Journal ofPharmaceutics, 236 (2002) 135-143Sotax, Introduction to USP 4 Method, powerpointWennergren, et al., A collaborative in vitrodissolution study: comparing the flow-throughmethod with the USP paddle method usingUSP prednisone calibrator tablets,International Journal of Pharmaceutics, 53(1989) 35-41AcknowledgementMost of the laboratory work was carried out atDFU (Danmarks Farmaceutiska Universitet)with Betty Lombstein Pedersen as supervisor.I’m grateful for all you help and guidance. Iwould also like to thank Anders Axelsson, myexaminer, Mariagrazia Marucci, SusanneFredenberg and Erik Kaunisto at theDepartment for Chemical Engineering, LTH(Lunds Tekniska Högskola) for helping mewith my diploma work and all my questions.ReferencesKällquist Sara, Frisättning av läkemedel iflow-through cell, 2007Nicklasson, et al., A collaborative in vitrodissolution study using the flow-throughmethod, International Journal ofPharmaceutics, 37 (1987) 195-200Nicklasson Martin, Industrial Aspects ofPharmaceutics – In vitro characterization ofdissolution rate (edited by Erik Sandell),Swedish Pharmaceutical Press, (1992) 64-79Shobha et al., Dissolution testing of a poorlysoluble compound using the flow-through cell