QBD

The Process of Powder Compaction In Relation To Variation of Excipient and Application of Qbd to Link Formulation to Development

The Process of Powder Compaction In Relation To Variation of Excipient and Application of Qbd to Link Formulation to Development

Introduction

Quality by Design (QbD) has been recognized as a superior pharmacological powder tablet manufacturing approach versus attempting to test in quality (Jeon, Gilli & Betz 2011). Without designing for quality, the level of quality has been observed to plateau well short of six sigma1 with diminishing returns on investment. This research quantitatively evaluates the phenomenon of a manufacturing sigma wall or quality plateau in the context of technological evolution, and demonstrates that QbD is superior to a quality by testing centric model (Michaut et al 2010). This research will consider QbD to include designing product and processes in terms of tableting based on compaction tableting by direct compression machine. This study will enable continuous improvement with the goal of achieving six sigma performances.

Excipients and application of QbD

Excipient are ingredients which help to keep the tablet intact in storage and then to dissolve at a particular rate after ingesting by the patient. Excipients include inactive ingredients such as binders, disintegrants, and lubricants. To elucidate if work-hardening has also attributed to the reduced tablet tensile strength, tablets are prepared with starting powder and roll-compacted granules of the same particle size. The tablets made by roll compaction showed no significant (P > 0.05) difference in tensile strength compared to direct-compacted tablets when the initial particle size is the same (Jeon, Gilli & Betz 2011). Two factors are considered as the main mechanisms of this phenomenon; particle size enlargement by granulation and work-hardening of materials due to limited binding potential. Also, the enlarged particle size by roll compaction seemed to be a main reason for the reduced tablet strength. This increased particle size might lead to lower tablet strength because of reduced surface area available for bonding (Bolhuis, Rexwinkel & Zuurman 2009).

Thus, the lower tablet tensile strength after roll compaction might be caused by mainly particle size enlargement rather than work-hardening (Michaut et al 2010). If more various and higher roll pressures are applied, it would become more clear whether work-hardening considerably occurred or not. In the formulation used and under the roll pressure employed in the present study (20 bar), the effect of work-hardening is not obvious. Further optimization of formulation has not been conducted in the current study because the final tablets made by roll compaction exhibited sufficient strength, although it is lower than that of direct-compacted tablets (Çomoglu 2010). However, the result obtained shows that in roll compaction the use of highly plastic excipients should be more carefully optimized than in direct tableting or wet granulation to minimize undesired loss of tablet strength. According to the literature, brittle materials are less sensitive than plastic substances not only to work-hardening but also to particle size difference (Michaut et al 2010).

In a study, it is observed that assay PpK at launch is ...