Tableting process case studies

This case study illustrates the SP method development of an assay method for a controlled-release analgesic tablet with a single API. Certain considerations were taken into account. First, the analyte within the tablet matrice core had to be extracted quantitatively. Second, the analyte was diluted into a final solution that was compatible with the HPLC mobile phase. Third, short SP time was required (i.e., 30 min) to maximize productivity of the work scheme for processing a large number of samples. 

To address the issue of the scale-up of the tablet compaction process, this chapter will review the following (1) compaction, (2) predictive studies, (3) scale-up/validation process, (4) case studies, and (5) process analytical technologies. 

This case study will summarize the development of a pan-coating process designed for the application of an enteric coating to a tablet product, provide insight into some of the early process optimization studies that were undertaken, and show how these ultimately facilitated the development of production-scale manufacturing processes. 

Cogdill, R. R, et al., (2005), Process analytical technology case study, Part II Development and validation of quantitative for tablet API content and hardness, AAPS Pharm. Sci. Tech., 6, Article 38. 

Case Study Scale-Up of a Wet Granulation Tableting Process... 

The principles of green chemistry by adopting the most efficient and environmentally friendly processes should be practiced whenever possible in the HPLC laboratory. One obvious approach is reduction of solvent consumption by using solvent recycling for isocratic analysis and narrowbore LC columns. Another area is to find ways to reduce sample size and the number of sample preparation steps without sacrificing method performance.2 A case study to illustrate this principle for a tablet assay is shown in Table 11.1. Another example is an environmental analysis of soil/sediment sample3 is shown in Table 7.7. 

Product bioavailability is mentioned, especially where it is low. Where there are differences between the formulations tested for bioavailability during the development process and the formulation to be marketed, there is considerable discussion of the data provided on the bioequivalence of the different products and/or formulations. This is particularly so where, for example, early clinical studies were undertaken with capsules but the marketed dosage form is to be a tablet. Bioequivalence data and pharmacokinetic data (e.g., in crossover studies) and comparative dissolution studies are usually reported. This is particularly significant where the different strengths of the final products are not achieved by using different quantities of the same granulate formulation. Process optimization may also be addressed in such cases. 

As with ordinary ATR spectroscopy, ATR-FT-IR imaging results can be analyzed quantitatively, some recent examples including the study of tablet dissolution in water. In this case, the concentration profiles of hydroxylpropylmethylcellulose (HPMC) and niacinamide, at different stages of the dissolution process, were utilized to provide an understanding of the drug release mechanism [54]. Using this technique, it could be shown that the concentration profiles of different components could be obtained with the partial least squares (PLS) method. Here, with... 

The tablet mass was fixed at 200 mg. Each unit contained 10 mg (5%) drug and 1.2% lubricant. It was considered that the lubricant level could be adjusted and optimized later as part of a process study. Thus, although there were 5 components in the mixture, 2 of them were fixed. The factor space in the remaining components, microcrystalline cellulose, lactose, and carbomer (totalling 93.8%) can be represented as a ternary diagram. The tablets were manufactured by direct compression of the powder mixture and the dissolution profiles were measured at pH 2 (0.01 M hydrochloric acid) and pH 7 (phosphate buffer). The time for 50% dissolution was measured in each case. 

Whether the desired end product is satisfactory can also be used as a practical criterion of the adequacy of the solids mixture. A further consideration is the effect of the solids mixture on the overall economics of the manufacturing process. Studies of the type mentioned in the preceding subsection may be part of such an evaluation. When the solids mixture is made directly into a product, as in the case of feed pellets or pharmaceutical tablets, uniformity tests on these items will speak for themselves. If the solids mixture must be further processed, as in the manufacture of glass or plastics, the efficiency and costs of the subsequent operations can often be related to the starting solids mixture. In such cases, knowledge of the homogeneity of the solids mixture is needed to determine its effect on the manufacturing process. 

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