EXPERIMENT 2TABLET DISSOLUTION AND DRUG RELEASELEARNING AIMS. ” .To oam ,amt11a . n’ty with tablet testing filTo ounderstand drug release . pro I esTo assess tablet dissolutionDIRECTED READINGAssessment of Dosage Forms· Physicochemical Principles of Pharmacy. Florence &Attwood, MacMillan 1988INTRODUCTIONA dissolution test is a mean of identifying and proving the availability of active drugmaterials in their delivered form. Many active materials are only required at themilligram or even microgram level in order to achieve the desire? p~armacolo?i~aleffect. As the delivery of a mg amount of active material to the subject 1s not realistic,we have to employ bulking agents in order to present medication in a form which iseasy to administer. These non-active bulking agents such as microcrystalline cellulose(e.g., Avicel) and silica (e.g., Aerosil) can have an effect on the way that the activematerial is released or what is referred to as its bioavailability.We need to define the availability of the active material as this will have a bearing onthe dosage available after ingestion. A dissolution test simulates this availability andallows the prediction of the time for complete release of the material from the dosageform. It also gives important Quality Control information as to how much of theactive material was in the dosage form and whether this concentration conforms to theexpected dosage.METHOD1. Switch on the dissolution apparatus with the water bath. Ensure temperature is setat 37°C.2. Fill three dissolution flasks with 900 ml of distilled water and allow to warm upto predefined temperature.3. Lower the paddles into the dissolution solution until they come to a stop. Theyshould not be touching the tablet or the base of the flasks.4. Set the paddle rotating speed at 50 rpm.5. Make sure the UV-spectrophotometer is switched on and is fully initialisedbefore taking any readings. Set the wavelength to 242 nm in fixed mode.6. To begin the test, drop one of the three paracetamol formulations provided intothe three flasks respectively (NB: there should be only one tablet in each flask).7. Start sampling immediately by pipetting 2 ml of the solution into clean cuvetteand measure the absorbance on the UV. Pour the solution back into the flasks aftereach measurement to keep volume constant.258. Take fu~er sample_s ~t 5 minute intervals for 60 minutes. Remember to rinse thecuvette with clean distlIIed water three times and shake out any water dropletsbefore the next measurement.NB: The UV absorbance ~ange is linear up to about 1.2 so please ensure yourreadings falls bel~w this value. If they are not, you may need to dilute thesolution before taking your readings. Carry on as follows.9. Dilute exactly I ml of each of the samples to 10 ml with distilled water and mixthoroughly.ATTENTION: further dilution may be required.IO. For each diluted solution, pipette 2 ml of the dilution into the silica cuvette. NB:Do not pour diluted solution back into the flasks. 1 ml should not affect the totalvolume significantly.RESULTSRecord your results as shown in the Table I. Assume each tablet contains 500 mg ofparacetamol. Use 648 as the Al % 1cm for paracetamol.Table 1: Dissolution results ime (mins)bsorbanceTablet 1051015202530354045505560 Concentration % Release(m)Plot data as % release versus time on the same graph. See the examples at the end ofthis script.QUESTIONSComment on your results by answering the following questions. You are looking fortrends/changes in the release rate and release profiles with variations such as tablethardness/ dosage form.• Which of the batch of tablets had the highest dissolution rates? Give reasons forthe difference. See the formulation constituents in Table 2 to inform your answers.26• What is the difference between prolonged, modified and sustained release dosageforms? What are the specifications for the above dosage forms and fastdisintegrating forms in terms of in vitro dissolution points and pH settings?• What is the meaning of the term sink conditions?ReferencesTable 2: Master ormula for the ormuIations • of paracetamo1used CapletsPanadol Tablets (Filmcoated)Panadol solubletabletsCapsulesParacetamolParacetamolParacetamolParacetamol–Maize starchStarchSodium bicarbonateStarch glvcolateSodiummetabisulphitePotassium sorbateSorbitol powderGelatineMagnesiumstearatePolyvidoneSodium lauryl sulphateMagnesium stearateTalcCitric acidSodium laurylsulphateStearic acidSodium carbonatepolyvidoneFILM COATINGCAPSULE SHELLHydroxypropylmethylcelluloseGelatineTriacetinTitanium oxidePropylene2:lvcol – –27D:Pical dissolution profileCONC.INSOLN.rate of non-disintegrating tabletdissolution determined by process ofdissolution and diffusion.disintegrating tabletrapid disintegration follow process ofdissolution and diffusioni.e. dissolution is rate-limiting.disintegratingslow disintegration/rapid processof dissolution and diffusioni.e. disintegration is rate-limiting.28j •
