Granulation variables formulation

A high-dose ( 75% drug loading) wet granulated tablet formulation was optimized using a DOE. The optimized critical formulation and process variables are shown in Table 10. 

According to the foregoing discussion, a large number of raw material and process variables must be considered when developing NPK production formulations that result in good granulation characteristics. As with the operation of an NPK granulation plant, formulation too, requires a considerable amount of skill and an element of art to ensure that the particular formulation will yield the desired results in a specific situation. 

High-shear granulation has been one of the most commonly used methods to produce granules since the early 1980s (4). Hence, this chapter discusses in detail, the equipment, process variables, formulation requirements, granulation end-point determination, and scale-up considerations of the high-shear granulation process. 

Tablet Formulations (Immediate Release). Two papers in the mid-1990s reported the earliest studies on immediate release tablets. In the first, tablet formulations of hydrochlorothiazide [33] were modeled in an attempt to maximize tablet strength and select the best lubricant. In the other, a tablet formulation of caffeine was modeled [34] to relate both formulation and processing variables with granule and tablet properties.

The approach taken here is to employ standard materials characterization tests to measure the materials properties of the granulated product. With this information, the mechanism of attrition, i.e., breakage versus erosion, is determined. The rate of attrition can then be related, semi-empirically, to material properties of the formulation and the operating variables of the process, such as bed depth and fluidizing velocity. 

Nevertheless, the acquisition of a sufficiently detailed body of physical information can allow a formulator to go far beyond the mere ability to cope with crises when they develop at unexpected times. For a well-understood system, it is theoretically possible to design an automated or semi-automated manufacturing scheme for which the processing variables would be appropriately controlled so as to minimize the possibility of batch failure. Materials passing the hurdles of physical test specifications would be totally predictable in their performance, and they could therefore be blended, granulated, dried, compressed, and delivered into containers without operator intervention. 

The samples from the plot receiving the granulated formulation (Table I) revealed a different situation. The overall variability was much larger with a coefficient of variation of 395, with increased variability both between and within the five samples. Analysis of variance gave components of 140 between field samples, and 264 between laboratory subsamples. Since the analytical procedures were identical with those used in the EC plot samples, where reproducibility was good, these results clearly indicate a much greater irregularity of the distribution of the herbicide in... 

Hontz J. Assessment of selected formulation and processing variables in fluid-bed granulation, Ph.D. Thesis, University of Maryland at Baltimore, (1987), Dissertation Abs. Int. (6), 1655-8(1987). 

In terms of the flow properties, the physics of compression, the variability of the dissolution and porosimetry parameters and the variability between trials, the wet granulated formula showed best results in almost all cases. This process is then proposed for the study of prolonged release formulations. 

Regardless of the stage of formulation/process development being considered, a detailed identification of variables and responses is necessary for early program planning. Typical variables and responses that could be expected in a granulated solid dosage form are listed in Table 1. This list is by no means complete and is intended only as an example. 

Faure A, Grimsey IM, Rowe RC, York P, Cliff MJ. 1999. Process control in a high shear mixer-granulator using wet mass consistency the effect of formulation variables. J. Pharm. Sci. 88(2) 191-195. 

The physical and mechanical properties of excipients were important variables in achieving performance of the final products as well. The preferred formulation strategy for a low-dose product using dry granulation is to design a cohesive blend to... 

Sheskey, P. J., and Hendren, J. (1999),The effects of roll compaction equipment variables, granulation technique, and HPMC polymer level on a controhed-release matrix model drug formulation, Pharm. Technol., 23, 90, 92, 94, 96, 98,100,102,104,106. 

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