Tableting of mini-tablets in comparison with conventionally sized tablets: A comparison of tableting properties and tablet dimensions

Abstract

Mini-tablets are solid dosage forms with increasing interest for pharmaceutical industry due to clinical and biopharmaceutical benefits. But technological aspects on mini-tableting are not fully investigated. Therefore, the impact of punch size and tableting pressure for industrially relevant excipients like microcrystalline cellulose, lactose, isomalt and Ludiflash® are investigated using 8 and 11.28 mm punches for conventionally sized tablets and 1,2 and 3 mm punches for mini-tablets. For evaluation of the effect of tablet size on deformation behaviour and mechanical properties, compressibility, compactibility and tabletability plots are created and evaluated. Deformation behaviour is analysed by In-Die Heckel plot and modified Weibull function. Further, specific plastic energy (SPE) profiles are generated out of force-displacement plots. The effect of the adjustment of the aspect ratio towards 1 as in conventionally sized tablets on deformation behaviour and tabletability is analysed. The effect of tablet size on deformation behaviour mainly showed lower yield pressures for conventionally sized tablets, whereas comparable SPEs were obtained with all tablet sizes. Furthermore, mini-tablets indicate better compactibility, as (depending on the excipient) higher tensile strengths were obtained at lower solid fractions. However, no superior tabletability properties are obtained for mini-tablets compared to conventionally sized tablets.

Implementing the Design of Experiments (DoE) Concept into the Development Phase of Orodispersible Minitablets (ODMTs) Containing Melatonin

“…The reason is the low hardness values of the analyzed ODMTs when compared to conventional or non-orodispersible minitablets and higher accuracy of the method. While difficulties in applying traditional hardness testers for ODMTs are recognized in the literature and texture analysis has been employed to determine crushing strength in several studies ( 1 , 19 , 22 , 27 ), to the authors’ knowledge up to date, no report has compared or modeled the results from the application of two testing methods. As demonstrated, both are correlated with each other and can be used for process characterization of ODMT compression, although texture analysis can be considered superior.…”

“…Interestingly, at higher compression force values, the response reaches a plateau, which suggests achieving maximum degree of plastic deformation and binding sites by the filler without fragmentation or brittleness which would compromise the ODMT's mechanical stability. To the authors' knowledge, such phenomenon has not been described for minitablet case studies, where usually linear increase in tensile strength was observed with increasing compression pressure (1,(18)(19)(20). This is likely explained by the differences in the used filler, as the cited works do not report the use of co-processed excipient GFD in this context.…”

“…However, to the authors' knowledge, reports of comprehensive approach to minitablets' formulation and process optimization in an industrially relevant setting are lacking in the publicly available literature, especially in the topic of ODMTs. While there are several valuable in-depth studies on formulation and compression of minitablets, they mostly focus on select narrow aspects, often employing placebo blends (2,(16)(17)(18)(19)(20) or equipment restricted to laboratory scale (eccentric tablet presses (4,16,17,21) or compaction simulators (18,19,22)). For the majority of the aforementioned research, the main focus has been on formulation characteristics, namely the choice of excipients type or grade, as well as particle sizes in the context of blend flow properties.…”

Pharmaceutical Development of Film-Coated Mini-Tablets with Losartan Potassium for Epidermolysis Bullosa

“…For LP to be used in paediatric patients, an appropriate dosage form is required. Mini-tablets, defined as tablets with a size of 2–3 mm and a surface-to-volume ratio of at least 2 mm −1 , represent a promising solid dosage form [ 16 , 17 ]. Various studies have indicated the acceptability and swallowability of single and multiparticulate 2 mm mini-tablets for the paediatric population; single-coated 2 mm mini-tablets were also tested [ 18 , 19 , 20 , 21 ].…”

Assessment of Mini-Tablets Coating Uniformity as a Function of Fluid Bed Coater Inlet Conditions

“…Mini-tablets are a novel and promising formulation, enabling the introduction of modified release medicinal products into pediatric therapy [ 37 ]. Moreover, because of their small size and easier production [ 38 ], they may represent a relevant replacement for pellets commonly used as a multiparticulate form of the drug. Therefore, research aiming to increase knowledge about the coating process of mini-tablets is an important topic in pharmaceutical technology.…”