Dosage form design scale

Block LH. Scale-up of disperse systems theoretical and practical aspects. In Lieberman HA, Rieger MM, Banker GS, eds. Pharmaceutical Dosage Forms Disperse Systems. Vol. 3. 2nd ed. New York Marcel Dekker, 1998 363. Astarita G. Scale-up overview, closing remarks, and cautions. In Bisio A, Kabel RL, eds. Scale-up of Chemical Processes Conversion from Laboratory Scale Tests to Successful Commercial Size Design. New York Wiley, 1985 678. Gekas V. Transport Phenomena of Foods and Biological Materials. Boca Raton, FL CRC Press, 1992 5-62. 

Effective product and process optimization play a prominent role in any successful scale-up study. As an illustration, this case study summarizes the initial development, and subsequent scale-up, of a Wurster process designed to facilitate the application of an aqueous ethylcellulose dispersion to drug-loaded pellets. At the same time, it was intended to deal, up front, with some of the idiosyncrasies of such a coating system that often influence the functionality of the final dosage form. 

Coming to grips with the multiplicity of parameters that commonly define such a process is clearly facilitated when employing statistical techniques exemplified by the design of experiments approach. Technology transfer on a global scale is equally well facilitated by access to expert systems that capture all of the relevant process and formulation events that have been used to define the final coated dosage form. 

Knowledge of the percolation threshold of the components of the matrix formulations contributes to improve their design. First, in order to develop robust formulations, that is, to reduce variability problems when they are prepared at industrial scale, it is important to know the concentrations corresponding to the percolation thresholds. The percolation thresholds correspond to formulations showing a high variability in their properties as a function of the volume fraction of their components. Therefore, in order to design robust dosage forms, the nearby of the percolation thresholds should be avoided. 

Fig. 3 shows a pilot plant layout with restricted personnel access. This design would support the development and clinical manufacture of solid dosage forms, liquids, semisolids, aerosols, and sterile products. Multipurpose rooms are incorporated in each area to maximize the use of portable equipment, and scale factors similar to those shown in Table 1 are employed. Isolation suites are indicated in the manufacturing area their purpose and design are discussed in more detail later. The sterile area is isolated from the main corridor by the interior corridor design. At the far left, the main corridor provides access for future facility expansion, if necessary. 

In the critical variables analysis phase, a statistical experimental design is created (e.g., factorial, Box-Behnken) intended to assess critical formulation and process variables in relatively small-scale manufacture. In these studies, the ranges of composition variables are chosen to at least encompass those noted in the recommendations of the AAPS-FDA Workshop on Scale-up of Immediate Release Oral Solid Dosage Forms or SUP AC. This phase is usually preceded by a development phase during which variables and levels to be studied are determined and the exact method of manufacture is established. Experimental formulations are assessed at least in terms of dissolution performance, content uniformity, and weight variation. On the basis of these studies, the specific formulations to be manufactured for biostudy are selected. 

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