Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Student: Šárka Hávová Supervisor: PharmDr. Jitka Mužíková, Ph.D. Title of diploma thesis: A study of compaction process and properties of tablets with hypromellose and α-lactose monohydrate Thesis studied the co-processed dry binder RetaLac® from the aspect of his compressibility and dissolution of the active ingredient from tablets. RetaLac® contains α-lactose monohydrate and hypromellose in the identical proportion. The same parameters were tested in the corresponding physical mixtures of FlowLac® 100 with various types of hypromellose (Metolose® 100 SR, Metolose® 4000 SR, Metolose® 100 000 SR) and compared with the substance RetaLac® . Compressibility was evaluated by means of the energy profile of compression and tensile strength of tablets. Salicylic acid was used as the model active ingredient. Dissolution testing was performed using the method of the rotating basket.

The thesis evaluates anhydrous and dihydrate calcium hydrogen phosphate from the view point of the tensile strength, disintegration time of tablets depending on the compression force. Two firm products - Anhydrous Emcompress® and Di-Cafos® A 60 are used as anhydrate and Emcompress® is used as dihydrate. A compression force together with lubricants (magnesium stearate, sodium stearyl fumarate) and an addition of microcrystalline cellulose (Vivapur® 102) are the influential factors. In addition to the characteristics of tablets, the energy balance of compression is also evaluated. Used compression forces were 12, 16 and 20 kN. The compression force 12 kN was used for the mixtures containing Vivapur® 102. Total energy of compression, energy for friction and energy accumulated by tablet after compression increased with compression force. The highest values were at Anhydrous Emcompress® , an addition Vivapur® 102 increased these values. There weren't more significant differences among the values of decompression energy. Plasticity decreased with the growing compression force, the highest values were at Anhydrous Emcompress® , Vivapur® 102 increased that. Tensile strength increased with compression force, Emcompress® provided the strongest tablets, Di-Cafos® A 60 provided at least strong tablets. Vivapur...

The thesis evaluates three types of anhydrous β-lactose combined with lubri- cants. The evaluation is made from the standpoint of compressibilty, tensile strength and ejection force, depending on the compression force used. Studied materials are Duralac H, SuperTab 21AN and Lactopress Anhydrous 250. Lubricants used in the concentration of 1% are magnesium stearate, glycerol-dibehenate and poloxamer 188. Compressibility is evaluated by the energy profile of compression. Total energy of compression increases with compression force used and de- pends on the type of anhydrous β-lactose and type of lubricant. Higher plasticity is shown by Duralac H and SuperTab 21AN. Ejection force is lowest in the case of Duralac H for all lubricants. Magnesium stearate appears to be the best lubricant for all types of anhydrous β-lactose. The effect of lubricants on the tensile strength of tablets depends on the compression force used. Highest values of disintegration time provides SuperTab 21AN, Duralac H with glycerol-dibehenate provides lowest values. 1

The thesis deals with the comparison of compressibility and properties of tablets containing silicified microcrystalline cellulose and physical mixtures of microcrystalline cellulose with different types of colloidal silicon dioxide. The used excipients were silicified microcrystalline cellulose Prosolv® SMCC 90, microcrystalline cellulose Avicel® PH-102 and colloidal silicon dioxide Aerosil® 200 and 255. Tablets were compressed at three compression forces 2.5, 3 and 3.5 kN. The energy profile of compression, the tensile strength of tablets and the disintegration time of tablets were evaluated. The effect of 1 % magnesium stearate on these parameters under various mixing conditions and its homogenity in the tablet were evaluated. Total energy of compression increased with the growing compression force, it was the highest at Prosolv® SMCC 90. Plasticity decreased with compression force, mixtures of Avicel® PH-102 with both types of Aerosil showed its the highest values. These mixtures provided tablets with lower strength than Avicel® PH-102 and Prosolv® SMCC 90. Disintegration time of tablets increased with the growing compression force and it was longer in the case of tablets from Prosolv® SMCC 90 and Avicel® PH-102. The addition of magnesium stearate decreased tensile strength of tablets most in...

La desintegració és una etapa important en la recuperació de paper vell, ja que té importants conseqüències en consum d'energia i en el comportament de les etapes posteriors.Per això els objectius es centren en analitzar la desintegració des del punt de vista del temps de desintegració, els aspectes energètics, modelització de la màquina de desintegració utilitzada i anàlisi dels factors de cisallament calculats com a mesura global de les forces implicades en la desintegració. Els autors que hi han treballat donen diferents explicacions a aquestes forces. Fins avui només s'ha pogut avaluar qualitativament la influència que tenen cada un dels mecanismes en el temps necessari per a desintegrar i en el consum energètic. Les característiques reològiques de les suspensions papereres, i el seu comportament no newtonià tenen una clara influència en el consum energètic i les forces de desfibrat en el desintegrador.Els experiments de desintegració s'han realitzat en un púlper convencional, amb tres tipus de paper recuperat: paper estucat d'alta qualitat imprès offset (PQ), paper revista estucat imprès en color (PR), paper blanc imprès en impresora làsser (PF).Anàlisi del temps de desintegracióPer cada un del papers estudiats (PQ, PR i PF), les fraccions màssiques des de 0.06 fins a la màxima que estat possible per cada paper (de 0.14 a 0.18), i a dues velocitats d'agitació diferents, s'ha determinat el temps de desintegració (tD) fins a aconseguir un índex de Sommerville de 0.01%. S'obté que en augmentar la fracció màssica disminueix potencialment el temps de desintegració. S'ha estudiat la velocitat de desintegració, la producció teòrica del púlper en cada cas, i la seva relació amb les forces d'impacte i de fregament que produeixen la desintegració.Aspectes energèticsEl consum específic d'energia (SEC), definit com l'energia consumida per a desintegrar 1 kg de paper recuperat, disminueix molt en augmentar Xm, ja que a més de disminuir l'energia consumida en cada desintegració, el contingut en paper és més elevat. Pel disseny de desintegradors, cal tenir en compte que en augmentar Xm i en augmentar la velocitat, sempre augmenta la potència consumida. Però així com els beneficis de treballar a Xm alt són de 10 vegades en termes de SEC i de producció, l'augment de potència és només de l'ordre de 2 vegades la necessària respecte de la Xm baixa. Viscositat aparent i energia de fluiditzacióS'estudia la relació entre el temps de desintegració, les forces de fregament i els valors de viscositat aparent de la bibliografia. Per cada paper i velocitat s'ha observat que el consum específic d'energia disminueix en funció de la viscositat aparent.Reologia del púlperUtilitzant el mètode de Metzner i Otto (1957) per determinar la viscositat aparent mitjana de les suspensions papereres, modificat per Roustan, s'ha caracteritzat el pulper mitjançant el model: Np= K· Rex·Fry S'han utilitzat dissolucions de glicerina com a fluid newtonià per a calcular les constants d'ajust, i a partir d'aquí, aïllar la viscositat aparent en funció de la potència neta i els paràmetres d'agitació.La viscositat aparent, d'acord amb Fabry (1999) es substitueix pel concepte de factor de cisallament.Factor de cisallamentCalculat el factor de cisallament per a cada paperot i condicions d'agitació, s'ha relacionat amb Xm, SEC, tD, consum de potència, potència instal·lada i fracció cel·lulòsica. El factor de cisallament és un paràmetre útil per a quantificar les forces globals implicades en la desintegració. / Disintegration is an important stage in paper recovery and it has important consequences in energy consumption and in the following stages.The objectives of this thesis are focussed in analyzing disintegration considering disintegration time, power aspects, modelisation of the disintegration machine and analysis of the calculated shear factors as a global measurement of the forces implied in the disintegration.Until now, it has only been possible a qualitative evaluation of the influence of every mechanism in the time necessary to disintegrate the pulp, and in the power consumption.Rheological characteristics of suspensions and their non-Newtonian behaviour it is known that clearly influence power consumption and defibering forces acting during repulping. Disintegration experiments have been made in a conventional pulper, with three types of recovered paper: high quality coated printed offset paper, magazine coated colour printed paper and white laser printed paper.Analysis of disintegration timeTime necessary to achieve a Somerville index of 0.01%, was determined for each paper studied, at mass fractions ranging from 0,06 until the maximum possible for each type of paper (0,14 or 0,18) and at two different agitation speeds. It has been found that when increasing the mass fraction, disintegration time decreases potentially. Disintegration speed and theoretical production of pulp have been studied in each case, and they have been related with friction and impact forces.Power aspects Specific energy consumption (SEC) defined as the energy consumed during disintegration of 1 kg of recovered paper, was reduced with increasing mass fraction (Xm), because the energy consumed during disintegration decreases and the pulp contend in the pulper is higher. And increase of Xm and pulper agitation speed always increases the power consumed. An increase of only 2 times of power consumption (due to working at high Xm) produces benefits in SEC and production of 10 times.Apparent Viscosity and fluidisation energy Relation between disintegration time, friction forces and apparent viscosity were studied. For each paper and speed it has been observed that SEC was reduced when increasing apparent viscosity.Rheology of pulper Using Metzner and Otto methodology to determine average apparent viscosity of suspensions, modified by Roustan, pulper was characterized by means of model Np=K·Rex·Fry. Glycerine dissolutions have been used as Newtonian fluid to calculate constants of adjustment, and from here, apparent viscosity was determined from net power and agitation parameters. Apparent viscosity, in agreement with Fabry, is replaced by the concept of shear factor.Shear FactorOnce calculated the shear factor for each type of paper and conditions of agitation, the values obtained have been related to Xm, SEC, td, power consumption, installed power and cellulose fraction. Shear factor is a useful parameter to quantify the global forces acting in disintegration process.