(W1030-03-16) Comparative Analysis of ‘All-in-One’ Co-processed Excipient Versus Its Proportional Individual Blend in the Production of Vardenafil HCl Tablets via Direction Compression

Purpose: The direct compression (DC) tableting process is often favored in comparison to other methods of tablet manufacturing. This is largely due to the method’s general simplicity and elimination of processing steps that are inherent to other production methods. An increasingly utilized asset in streamlining the DC process is the usage of coprocessed excipients. Coprocessed excipients are manufactured by combining several excipients into a single highly functional material. This study compares the processibility and tabletability of coprocessed vs. non-coprocessed placebo and active blends. The “all-in-one” coprocessed excipient tested was Kollitab^TM DC 87 L, with comparable raw materials that are included in its composition. Kollitab’s composition are: Kollicoat^® IR (copolymer of polyethylene glycol and polyvinyl alcohol) as binder, crospovidone as disintegrant, lactose monohydrate as filler/diluent, and sodium stearyl fumarate (SSF) as its lubricant. To further scrutinize the properties of this coprocessed material versus its individual component blend, we included in comparison trials the addition of a micronized, cohesive, and poor flowing API, vardenafil HCl, a phosphodiesterase-5 inhibitor indicated to treat erectile dysfunction¹.

Methods: Coprocessed “all-in-one” excipient Kollitab ^TM DC 87 L (BASF) was directly compared with an individual blend of excipients that would contain all components required for tableting via direct compression. The individual raw material blend included copovidone (BASF) as binder, crospovidone (BASF) as disintegrant, lactose spray-dried (DFE) as filler/diluent, and SSF (JRS) as lubricant, at the same proportion as reported in Kollitab™ DC 87 L. The blend components except for the lubricant were combined and blended for 15 minutes at 19 RPM in a V-blender. SSF was added and manually mixed for 2 min in a plastic bag. For blends containing vardenafil HCl, the API was sieved individually with a 0.6 mm mesh, weighed, and added to Kollitab^TM DC 87 L, or with the individual raw materials and blended for 15min at 19RPM. Tablet Production - All trials were manually fed into a Korsch XL 100 tablet press, compressed using 9 mm round punches, at a turret speed of 20 RPM. The target tablet weight was set at 250 mg. The compression forces used for tablet production were 3,7,10, and 12.5 kN. Evaluating Powder Flow Properties - Tapped and bulk densities were measured by protocols outlined in USP ( < 616 > Bulk Density and Tapped Density of Powders2. Hausner ratio was calculated by dividing tapped density by bulk density. An Erweka GTB was used to measure the angle of repose and powder flowability through funnel hole sizes. Blend samples of ~40g were evaluated with a 480mL funnel for each recording. The nozzle size can indicate blend flowability in small orifices, such as those within the fill cam of the tablet press. Samples were tested in triplicate. Hausner ratio and angle of repose analysis were performed based on the USP procedures ( < 1174 > Powder Flow)³, as well as the evaluation of their results. A FT4 powder rheometer was utilized to determine materials compressibility percentage (CPS%) at 15 kPA, cohesion, unconfined yield strength (UYS), major principal stress (MPS), and flow function (FF) of all tests. Samples were tested in triplicate. Evaluating Tablet Properties - For each compression force, tablet hardness, weight, and thickness were measured with an Erweka GmbH with a sample number of 20 (N=20). Tablet friability was performed using the USP guidelines ( < 1216 > Tablet Friability)⁴.

Results: Kollitab™ DC 87 L provided better flowability compared to the individual raw material blend, based on the results of the FT4 powder rheometer, angle of repose and Hausner ratio. Kollitab™ DC 87 L blended with vardenafil HCl at 10% drug load also presented superior flow when compared to the individual raw material blend (Table 1). The tableting performance and resulting quality of tablets produced by DC of pure Kollitab™ DC87 L and the individual blends and their mixture containing 10% drug load were scrutinized. Difficulties including tablet capping and punch sticking were recorded during production of tablets derived from the individual component blend with 10% vardenafil HCl. Pure Kollitab™ DC87 L tablets and Kollitab™ DC 87 L + vardenafil 10% tablets were found to have increased hardness at the higher range of compression forces tested and more consistency in tablet mass versus the respective alternative blend (Figure 1). Friability testing revealed that individual blend tablets failed USP standards at 3 kN, with and without API, and lost 3-10x more mass during testing than respective Kollitab^® DC 87 L tablets at all but the highest compression force tested (Table 2).

Conclusion: Here we find that the ‘all-in-one’ co-processed excipient Kollitab™ DC 87 L presented superior flowability and processability than the blend of individual components, including for the vardenafil blends. The results demonstrated that this co-processed “all-in one” excipient has application benefits and processing advantages in direct compression over a physical mixture of its proportional individual components.

References: 1 – Drug Bank: https://go.drugbank.com/drugs/DB00862
2 – United States Pharmacopeia (2022). General Chapter, 〈616〉 Bulk Density and Tapped Density of Powders.
3 – United States Pharmacopeia (2022). General Chapter, 〈1174〉 Powder Flow.
4 – United States Pharmacopeia (2022). General Chapter, 〈1216〉 Tablet Friability.

Table 1: FT4 and powder flow results of vardenafil HCl, Kollitab™ DC 87 L, individual raw material blend, and their active blends containing 10% vardenafil HCl.



Figure 1: Manufacturability profile and tablet weight variation of Kollitab™ DC 87 L, individual raw material blend, and their active blends containing 10% vardenafil HCl



Table 2: Friability results