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...

Clarification of various factors affecting the quality characteristics of product and establishment of an acceptable range of characteristics play an essential role in stable manufacturing of the sophisticated and desired products. Wet mass properties during agitating granulation process provide strong influence on the quality of final products, and this process is widely used in the pharmaceutical, the plastic and the foods industries. However, agitating granulation process is associated with many operating parameters, which can be classified as apparatus variables (vessel shape and impeller shape), process variables (method of binder addition, wet kneading time and impeller speed) and product variables (powder properties, formulation and binder liquid volume). Both the evaluation of wet granulation and the analysis of observed behavior are very difficult.Many researchers [1][2][3][4][5][6] have studied the determination method for the critical parameters involved in wet granulation and wet kneaded mass; furthermore, they investigated the effects of such parameters on the granule size, its distribution and density. Although properties of wet granules are not directly and universally quantified by using the torque rheometry and power consumption measurements specific to respective machines, some attempts 7-9) have been carried out on the evaluation of granulation and its end point determination. Nevertheless, few reports have focused on the related properties of the wet kneaded mass to the dissolution of sustained-release drug despite of the fact that many different types of sustained-release dosage forms are urgently needed by medical circles to improve clinical efficacies and relevant patient compliance. 10)Watano et al. [11][12][13] have recently demonstrated that properties of the wet kneaded mass are directly characterized by internal pressure transmissions which are determined by using a newly developed compression tester instead of the torque rheometry. Furthermore, it was also documented that the pressure transmissions were strongly associated with water dispersion among the wet kneaded mass. Despite of these available findings, however, the pressure transmissions of the wet kneaded mass are not well identified. What's worse, to make full use of the features of the wet kneaded mass for manufacturing the sustained-release dosage forms, e.g. wax matrix products, all we have to do is to address the relationship between the pressure transmissions and the drug dissolution. In the present study, the author managed to expand the pressure transmission to the form of the rheological behavior to identify the character of the transmission. Scrutinized investigations about the expanded pressure transmission disclosed the plastic property of the wet kneaded mass that turned out to be the most decisive and direct criterion in the kneading process control. It is because the kneading process subjects the powder sample to be plastic for the preparation of the extrusion granulation. From a theoretical point of view, the e...