Granulation Liquid

Power dissipation can lead to temperature increases of up to 40°C in the mass. Note that evaporation of liquid as a result of this increase needs to be accounted for in determining liquid requirements for granulation. Liquid should be added through an atomizing nozzle to aid uniform hquid distribution in many cases. In addition, power intensity (kW/kg) has been used with some success to judge granulation end point and for scale-up, primarily due to its relationship to granule deformation [Holm loc. cit.]. Swept volume ratio is a preliminary estimate of expected power intensity. 

Pepin, X., Simons, S.J.R., Blanclion, S., Rosstti, D. and Couarraze, G., 2001. Hardness of moist agglomerates in relation to interparticle friction, granule liquid content and nature. Powder Technology, 117, 123-138. 

A comparison of the measured mean relative size with the model in Eq. (101) is shown in Fig. 28. The material was monosize glass beads. The data fit the model quite well, with the exception of fine 0.038-mm powder. It is evident that the steady-state size distribution is a function of the liquid content, and consequently, as shown by Sherrington (S9), there is an optimal granulating liquid for maximum granulation efficiency, that is, percentage of the product-grade material. 

Porosity calculations from density measurements have also been applied to granulations prepared using different processes. The method of granulation, such as the type of adjuvant used [64] or the amount of granulation liquid [74], was found to change the bulk density and porosity of the material. Consequently, the compression and flow properties of the materials were also different. 

III. Calculation of the feed rate of granulating liquid, Hungarian ]. Ind. Chem., 1 (1973b) 463-474. 

Prepare a sample of the granulating liquid and pump it into a separate vessel. Determine the percentage of granulating liquid transferred. Determine the pump losses. 

Determine the effective liquid flow per minute by pumping a normal production granulating liquid at fixed dosing speeds. 

The batch size ranged from 3.75 up to 60 kg. To obtain precise scale-up measurements, the excipients which were used belonged to identical lots of primary material [10% (W/W) corn starch, 4% (W/W) polyvinylpyrrolidone as binder, and 86% (W/W) lactose]. As can be seen from Figure 4, the amount of granulating liquid is linearly dependent on the batch size. During the scale-up exercise, the rate of addition of the granulation liquid was enhanced in proportion to the larger batch size. Thus the power profile, which was plotted... 

For a fixed coefficient of friction p. and a fixed dimensionless shear rate K, the measurement of the power consumption per unit volume of the moist powder mass is proportional to the cohesive stress Uc- Thus, if the granulating liquid is added to the powder mass at a constant rate, the power consumption profile describes in a first approximation the cohesive stress (Tc as a function of the relative saturation S of the void space between the particles (Fig. 5). 

With dosage form design, it is often necessary to compare the performance of two different granule formulations. These two formulations differ in composition and, as a consequence, vary also in the amount of granulating liquid required. 

Thus, the following question arises how can the quantity of granulating liquid be adjusted to achieve a correct comparison ... 

The answer is not too difficult, as it is based on identified physical principles. A correct comparison between two formulations is often a prerequisite, as the dissolution process of the active substance in the final granulate or tablet can be affected both by the amount of granulating liquid and the qualitative change (excipients) in the formulation. In order to calculate corresponding, i.e., similar amoimts of granulating liquid in different compositions, it is necessary to introduce a dimensionless amount of granulating liquid n. This amount n can be defined as degree of saturation of the interparticulate void space between the solid material (Fig. 2). 

The physical characteristics of the starting materials are compiled in Table 1. Polyvinylpyrrolidone was added in a dry state to the powder mix of lactose and corn starch at a level of 3% (w/w). As a granulating liquid, demineralized water was used and pumped to the powder mix at a constant rate of 15g/min/Kg. 

Dry blending of the primary powder material, i.e., active substance and auxiliary substances in a mixer. Preference should be given to demineralized water as granulating liquid and the excipients and the drug should show relatively low water solubility with the exception of the binder. The binder should be preferably added in a dry state as part of the powder components. 

Depending on the formulation and on the properties of the components in the powder it may be necessary to mass the moistened powder for some time before screening. However, it has to be checked as to whether the massing process can be avoided if the granulating liquid is pumped into the powder bed at a reasonable rate. 

Figure 9 Cumulative particle size distribution of the agglomerates at a fixed normalized amount n (=0.62) of granulating liquid for different ratios of the binary powder mixture lactose/corn starch.

Usteri M, Leuenberger H. Granulation with surfactants effect of the chemical nature of the surfactant and the starting material on the granulating liquid requirement. Acta Pharm Technol 1989 35 163-167. 

Scaling-up by maintaining the droplet size of the granulating liquid will enhance the probability of an uniform nucleation stage to build the granules. 

Baert L, Remon JP. Influence of amount of granulation liquid on the drug release rate from pellets made by extrusion spheronization. Int J Pharm 1993 95 135-141. 

Robust formulations are today an absolute prerequisite. Concerning the production of granules, the granule size distribution should not vary from batch to batch. The key factors are the correct amount and the type of granulating liquid. The interpretation of the power consumption method can be very important for an optimal selection of the type of granulating liquid. The possible variation of the initial particle size distribution of the active substance and/or excipients can be compen-... 

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