Direct compression is a faster, simpler, and easier technique for tablet manufacturing compared to other processes such as wet and dry granulation techniques because it only requires mixing and compression. In addition to mixing and compression, wet granulation requires granulation, drying, and milling. Each additional step generates variability in the process and increases the risk of out-of-specification products. Fewer steps in the manufacturing process are advantageous for pharmaceutical industries; however, the application of direct compression has been limited due to issues of powder flowability, content uniformity and tabletability. A failure of powder flow often leads to abandon direct compression and adopt granulation process during formulation and process development trials. Flow has a direct impact on decision of whether to start out developing direct compression. Additionally, flowability and tabletability often develop into critical quality factors of high-dose tablets, while content uniformity causes the major concern in low-dose tablets. 1)Therefore, unfavorable powder flow is the fundamental and serious bottleneck to be first eliminated in the direct compression processing.Glidants are usually incorporated in direct compression formulations to improve powder flow and control tablet weight. Specifically, silica has been reported to be the most efficient glidant because of its small particle size and extremely low-density.2) Moreover, direct compression vehicles, such as spray-dried lactose and agglomerated lactose instead of fine-powder lactose, are commonly used to remedy flow properties. Several studies have reported that powder flowability can be significantly enhanced with the optimum concentration of porous or nonporous silica, 3) appropriate mixing time, 4) correct mixer type 5,6) and hydrophilic or hydrophobic silica properties.7) However, most of the studies have focused only on the relationships between the glidant and the direct compression vehicles and have excluded an active pharmaceutical ingredient (API), even though API powder properties are quite different from these excipients for direct compression. Generally, APIs are micronized to improve solubility and bioavailability, and consequently tend to be cohesive. In contrast, the direct compression vehicles are usually agglomerated and enlarged to become free flowing. Therefore, micronized API and enlarged direct compression vehicles are the most interesting and noteworthy factors to comprehensively improve the flow properties of a direct compression formulation. Shear mixing plays a critical role in blending for direct compression, particularly for low-dose drug products containing lubricants (e.g., magnesium stearate and calcium stearate). The homogeneity of the low-dose API requires sufficient mixing and results in excessive shear on magnesium stearate. The excessive shear mixing of the lubricant reduces the mechanical strength of the direct compression tablets by producing a surplus coating of the finely divided magnesium stearat...

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Kinesins are microtubule (MT)-based motor proteins that power intracellular transport. By using the 3-D tracking microscopy we develped, it was shown that MT rotates in a left-handed manner with the pitch of ∼0.3 μm when it slides on the lawns of single-headed kinesins. We here introduced mutations at the N-terminal region which was proposed to interact with the necklinker as a cover strand (CS) form to build a β-sheet. By tracking quantum dot attached to MT, the corkscrewing motion of MT driven by mutants were directly and quantitatively visualized in 3-D. The pitch depends on the type of mutations, indicating that one of the structural bases that causes torque is CS.