Quality by Design (QbD) philosophies of generating a true product and process understanding encourage the concept of intrinsic reliability and reproducibility of manufacturing processes . This is particularly relevant to modified-release preparations where too rapid or too slow release of drug can compromise safety or efficacy. It will be evident from previous comment in this chapter and information elsewhere in this book that multiparticulate-controlled delivery systems offer many possibilities for designing a variety of release modes. Multiparticulates can be converted to tablets by compression or can be filled directly into capsules. The latter operation carries little or no risk that mode or rate of drug release is altered. By contrast compaction stress carries the risk of coat rupture, or of altering the porosity of a matrix pellet. At the same time, compaction can reduce unit size due to the greater compact density. Processes or operating parameters and variabilities need to reflect such considerations.
Principles, processes, and associated equipment and monitoring systems for development and manufacture of coated pellets are well established [37-39]. Recent advances in pellet formation strategy as suggested by Roblegg using a single-component pellet system formed by calcium stearate and ibuprofen  and innovative dry powder coating technology  provide opportunities for additional process simplification and efficiency enhancements.
Tableting of pellets can be complex and multifaceted. Various factors have been shown to impact product quality and performance. Optimization may be difficult due to the complex nature of pellets, the need for excipients to aid tableting as well as the compression process per se. Bodmeier  reviewed the tableting of coated pellets and concluded that "the challenges of preparing tablets from coated pellets are evident." Later articles confirmed the challenge of compressing coated pellets to a tablet [43-46].
Abbaspour et al. investigated pellet load and compression force on friability, hardness, and disintegration of tableted pellets. Disintegration times of 7 min, being equivalent to usual capsule disintegration times, could only be achieved with a maximum pellet load of 60% and low compression force (5 kN). Hardness of resulting tablets was only just above the minimum requirement . Friability can also be poor .
Encapsulation of multiparticulates into HC is a single-unit process allowing pellets to retain integrity during processing. A capsule technology platform allows filling of many kinds of modified-release drug delivery systems, like pellets, granules, mini-tablets and combinations thereof. In contrast to tableting, the encapsulation process is only dependent on a few parameters like pellet size, shape and the tendency to form aggregates. These do not normally compromise content uniformity and can be predetermined using computer simulation [49-51]. Fill-weight monitoring during encapsulation can accordingly be utilized as a Process Analytical Technology (PAT) tool for content uniformity assurance.
Many controlled-release products are marketed in several dose strengths. The above-mentioned morphine sulfate extended-release product (Kadian®) is available in eight different strengths from 10 to 200 mg in capsule presentations . Due to the variety of different drug delivery technologies and combinations thereof, the number of available capsule sizes, their diversity in terms of color, color combinations or imprints which is critical for product safety, especially in polypharacy conditions  and the ease of dose adjustment on filling machines, a capsule technology platform provide flexibility and efficiency in development and manufacturing (Fig. 14.10).
A lean and simplified process is directly related to the number of unit operations and hence resources and input materials needed. Fewer unit operations and fewer excipients contribute to cost-efficient manufacturing .
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