MILITARY PHARMACY AND MEDICINE

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© Military Pharmacy and Medicine • 2012 • 4 • 28 – 32pharmaceutical availability of medicinal substances,and thus the efficacy of treatment.The assumption behind the study was to attemptmodification of pharmacopoeial anhydrousabsorption base, i.e. hydrophilic vaseline, by theaddition of novel cholesterol oxyethyleneationproducts manufactured by the Surface ActiveAgents Production Plant ICSO Blachownia inKędzierzyn-Koźle [5,6,7]. The novel base withvariant compositions was proposed as a carrier forketoprofen — a medicinal substance with analgesic,anti-inflammatory and antipyretic activity [8].The main indications for local application ofketoprofen include muscle and joint pains,inflammatory conditions caused by injuries suchas joint dislocations, sprains or sports injuries,and tendonitis [9]. Local administration of ketoprofendetermines its activity in pathological tissuesand minimizes the risks of adverse eventsreported for oral use [10].ObjectivesThe goal of the study was to assess the effects ofcholesterol oxyethyleneation products on rheologicalparameters of hydrophilic vaseline-basedointments and the efficacy of the release of a nonsteroidalanti-inflammatory drug available aslysinate salt into the external compartment.Reagents and equipmentReagents:••hydrophilic vaseline (Coel);••ketoprofen lysinate (Sigma);••cholesterol oxyethyleneation products containingthe following numbers of oxyethylenicsegments (n TE ); 10, 20, 30, 40 (productsmanufacture using a sodium catalyst) and 10for calcium catalyst (Surface Active AgentsProduction Plant ICSO Blachownia inKędzierzyn-Koźle);••distilled water.Instrumentation:••MR 200 formulation mixer (Alpina);••water bath MLL 147/6 AJL (Electronic Krakow,Poland);••Cone/plate DV-III digital rheometer, version3.0 (Brookfield);••bath thermostat PGW E1 (Medingen);Original article••extensometer, pH-meter N5170E with ERH-131electrode (Hydromet Gliwice, Poland);••drug release apparatus Erweka DT 600(Erweka), apparatus accd. to Mutimer et al.;••Visking Dialysis Tubing C/100 membrane,wall thickness 74 μm and pore diameter 75 μm(Serva Electrophoresis GmbH);••spectrophotometer Nicolet Evolution 300,version 1.0 (Spectro-Lab);••technical balance (Radwag, PrecisionMechanics Plant in Radom, Poland), analyticalbalance (Radwag, Precision MechanicsPlant in Radom, Poland).Experimental methodDevelopment of model formulae5 model ointments were prepared with theabsorption base consisting of hydrophilic vaselinemodified with cholesterol oxyethyleneationproducts. The formula of the ointments is presentedin Table 1.Table 1: Formula of the ointments with the absorptionbase consisting of hydrophilic vaseline modifiedwith cholesterol oxyethyleneation products.IngredientKetoprofen lysinateHydrophilic vaselineCholesterol oxyethyleneation product *Distilled waterQuantity (g)2.576.51.020.0* Oxyethyleneation products used included products prepared using a sodiumcatalyst had the following numbers of oxyethylenic segments: n TE=10 (M-Ch-10 Naointment), n TE=20 (M-Ch-20 ointment), n TE=30 (M-Ch-30 Na ointment), n TE=40(M-Ch-40 Na ointment) and the product of n TE=10, prepared using a calcium catalyst(M-Ch-10 Ca ointment).For comparison, an ointment containing no cholesteroloxyethyleneation products was also prepared(M-0 ointment). The formula of the ointmentsis presented in Table 2.Table 2: The formula of the ointments with hydrophilicvaseline base.IngredientKetoprofen lysinateHydrophilic vaselineDistilled waterQuantity (g)2.577.520.0Ointment extensibility testThe test was conducted at 25 °C using the extensometricmethod.28 http://military.isl-journals.com
© Military Pharmacy and Medicine • 2012 • 4 • 29 – 32Justyna Kołodziejska at al.: Cholesterol oxyethyleneation products as …Determination of ointment viscosity parametersOintment viscosity tests were conducted at32 °C±0.1 °C using a cone/plate digital rheometercoupled with a bath thermostat [12].Determination of the kinetics of the loss of volatileointment componentsPlates with the diameter of d=9cm and totalsurface area of P=63.59 cm2 were covered withuniform ointment layers. Thus prepared sampleswere placed in a dryer-balance at 32±0.1 °C for2.5 and the percentage weight loss readings weretaken every 15 minutes.Determination of the kinetics of the release of lysinatefrom the ointmentThe test was conducted using the technique usedfor transdermal therapeutic systems according toPh.Eur. 6 requirements [13].Figure 1: The relationship between the applied load and the observedincrease in M-Ch-30 Na ointment surface area.Figure 2 compares the extensibilities of all testedointments under the highest load applied duringthe test (227 g).A 5 g ointment sample was placed in a dialysiscontainer with the mass exchange surfaceP=19.625 cm 2 (apparatus accd. to Mutimer etal.). Next, the ointment surface was covered byan appropriately prepared Visking dialysis membrane.Before the test, the dialysis membrane wasexposed to distilled water over 24 h. The entiresystem was closed with the lid and tightened withnuts. Thus prepared dialysis container was placedin a thermostated vessel (32°±0.1 °C), containing0.25 dm 3 of distilled water as a recipient liquid.The solution above the container was put in continuousrotational motion using a stirrer rotatingat 100 rpm. The mass exchange rate was measuredby spectrophotometric analysis of ketoprofenlysinate released from the ointment. Measurementswere made at nine time points over 6hours (samples collected at 40-minute intervals).The amount of the released ketoprofen lysinatewas determined at λ=260 nm using the followingequation: A= 0.4249·c+ 0.0677 (r=0.9991), where:A is absorbance and c is the concentration of thepharmaceutical substance.Results and DiscussionResults of extensometric testsExtensometric tests (measurements of extensibility)allowed to assess products’ capacity toincrease its surface area under the pressure force.Figure 1 presents an example extensibility curve(relationship between the extended ointmentsurface area and the force load applied).http://military.isl-journals.comFigure 2: Comparison of extensibilities of all tested ointmentsunder the highest load applied during the extensometrictest.Extensibility is the measure of product’s capacityto increase its surface area under increasingpressure force. Products of high extensibility areeasily distributed over the administration site.This affects the quality of application. Administrationof ointments on inflamed tissues shouldnot increase the pain sensation. Good extensibilityof the ointment increases the rate of release ofthe active substance at the site of administration.Diffusion of the active substance into the externalcompartment may occur over a large ointmentsurface area that has been spread using alow pressure force.Modification of the absorption base (hydrophilicvaseline) by introduction of novel cholesterol oxyethyleneationproducts increased the extensibilityparameters of all prepared ointments (Fig. 2).In case of ointments prepared using novel ointments,and in case of the highest loads appliedduring the extensometric tests, the surface areasof extended ointments ranged from: 3.61 to 4.52c.u. In case of the ointment with unmodified formula(M-0), the value was 3.15 c.u.29
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