MILITARY PHARMACY AND MEDICINE

© Military Pharmacy and Medicine • 2012 • 4 • 30 – 32Viscosity test resultsFigure 3: Hysteresis loop for the M-0 ointment.Ascending curveDescending curveOriginal articlewere performed by increasing the shear rate fromzero to a pre-defined maximum value and thanback to zero immediately after reaching the maximumpoint. Figures 3 and 4 present examplehysteresis loops obtained for the M-0 ointmentand for an ointment containing a cholesteroloxyethyleneation product (M-Ch-10 Na).Positive tixotrophy was observed for all preparedproducts. Upon isothermal flow of the fluid thathas previously been in stasis for a prolonged time,the shear stress was reversibly reduced over timein these systems.Structural viscosity of the tested ointments wascompared at the ascending hysteresis loop curvefragments for three arbitrarily selected shearrates of 12.2, 24.2 and 30.2 1/s. The results arelisted in Table 3.Figure 4: Hysteresis loop for the M-Ch-10 Na ointment.Ascending curveDescending curveViscosity tests showed that all hydrophilic vaseline-basedointments with variant compositionswere tixothropic and rheologically unstable, asconfirmed by the hysteresis loop test [14]. Measurementsof shear stress depending on shear rateTable 3: Structural viscosity parameters for the model ointments.OintmentShear rate12.2 1/sShearstress[N/m2]Viscosity[mPa·s]Shear rate24.2 1/sShearstressViscosity[N/m[mPa·s]2 ]Shear rate30.2 1/sShearstress[N/m 2]30 http://military.isl-journals.comIntroduction of cholesterol derivatives into theformulae of hydrophilic vaseline-based ointmentsreduces their structural viscosity values,as observed at all three shear rates tested in thestudy. Based on the Einstein-Smoluchowskiequation: D=kT/6πrη, (where: D — diffusivityof the medicinal substance, k — Boltzmann constant,T — temperature in Kelvins, r — observedradius of the molecule of the medicinal substance,η — viscosity) [15], one may expect that thereduction in viscosity parameters wouldenhance diffusibility of the medicinal substance(ketoprofen lysinate) from the ointmentinto the external compartment, which isassociated with increased anti-inflammatoryefficacy of the product.Viscosity[mPa·s]M-0 52.5 4286 49.7 2054 50.5 1672M-Ch-10NaM-Ch-20NaM-Ch-30NaM-Ch-40NaM-Ch-10Ca47.5 3895 24.5 1010 23.9 789.942.3 3471 30.4 1257 30.2 99444.1 3618 28.2 1167 29.6 980.852.1 4269 39.2 1618 42.9 142251.1 4188 40.0 1651 38.8 1284Water loss kinetics test resultsThe measurements of water loss kineticsconstitute a supplement to the rheologicaltests (extensibility, structural viscosity). Theointment’s tendency to lose water affects itsstructural viscosity following applicationon the skin, and thus, the kinetics of therelease of the active substance. From thisstandpoint, slight viscosity changes arepreferred over time. The measurements ofthe water loss kinetics may also be used toassess the rheological stability of the productas part of stability tests. Slight changesin the ointment mass occurring over time