Understanding the Factors That Control the Quality of Mini-Tablet Compression: Flow, Particle Size, and Tooling Dimension

A Novel Use of Nanocrystalline Suspensions to Develop Sub-Microgram Dose Micro-Tablets

“…It is suggested that the d 90 value of the granules should be equivalent to 1/3 rd of the die-hole diameter, and the d 50 value of the granules shouldn't be more than 10% of the diehole diameter to aid in consistent die-filling, thereby reducing the weight variability among individual micro-/mini-tablet units. 8,20 In the current study, the ratio of die-hole diameter to the particle size of the blend (d 50 ) was ~13, indicating acceptable particle size of the blend to ensure the production of micro-tablets with good quality. The API loading and the API particle size did not impact the particle size distribution of the final blends; this can be attributed to very low API loadings.…”

“…The %RSD values ranged from 1.9% to 3.5% for all the batches. No specific trend was observed with respect to API particle size and loading in the weight variability results; this was anticipated as all the lubricated blends resulted in similar PSD and ffc values, which are deemed as essential contributors to achieve consistent die filling, 20 thereby uniform tablet weights. The %RSD values in the current study were tight, indicating good weight control for individual micro-tablets'.…”

“…In addition to the discussed concerns of the respective approaches, the application of the approaches mentioned above to manufacture of low dose micro-/mini-tablets can be further challenging due to the additional requirements like superior powder flow and maintenance of adequate die-hole diameter to blend particle size ratio (typically high) to ensure consistent and reproducible die filling that are essential pre-requisites to ensure good micro-/mini-tablet quality. 8,20 For example, i) reduction in API particle size to improve CU may result in increased cohesion, segregation, and flow issues [21][22][23] impacting the process of die filling during the direct compression process, ii) granulation of micronized API to improve flow and CU may lead to oversized granules if process parameters were not adequately controlled, resulting in lower die-hole diameter to particle size ratio which subsequently leads to die-filling issues and thus the production of micro-/ mini-tablets of poor quality 20 iii) particle size differences between the drug particle or drug-carrier composite and excipients might lead to segregation.…”

Effects of Manufacturing Process Variables on the Tablet Weight Variation of Mini-tablets Clarified by a Definitive Screening Design

“…By contrast, to date, several studies have reported that several powder properties, mainly flowability, have a significant impact on the mini-tablet weight variation. [19][20][21] These previous studies have tested sample powders having a wider range of powder properties compared with the granules used in the present study, resulting in the detectable effect on the powder properties. We also think that other process variables, other than the granulation process, significantly affected the tablet weight variation.…”

“…[15][16][17][18] In addition, there are several reports that powder properties (particle size, powder density, flowability and others) affected the weight variation of mini-tablets. [19][20][21] However, systematic knowledge concerning the weight variation of mini-tablets is yet to be obtained. From these perspectives, the present study investigated the relationships among process variables of fluidized bed granulation, granule properties and weight variation of mini-tablets.…”