(M1230-09-51) Formulating Sustainable Solid Oral Tablets by Employing Digital Tools and Co-Processed Excipients

Purpose: Sustainability goals can be achieved by reducing product development R&D time, lab trials, equipment usage, and electrical power consumption. This study demonstrated how the use of both algorithm-based, predictive digital tools, like Zoomlab^® and all-in-one co-processed excipients, like Kollitab^TM DC 87L,  yielded significant reductions in these areas while developing omeprazole tablets.

Methods: Omeprazole was acquired from Teva Pharmaceutical Industries Inc. and other excipients were characterized for particle size distribution (PSD), bulk density, tapped density, angle of repose, compressibility and compactibility. The algorithm-based Developability Classification application in Zoomlab® was used to calculate solubility, absorption and permeability parameters for the material, based on chemical attributes imported from PubChem and physical properties of the specific material measured in the lab (i.e. true density, D₉₀ value and Solubility in FASSIF at 37^o C). In another algorithm-based application the processability of the omeprazole was analyzed using API data acquired in the lab (i.e. PSD, bulk density, tapped density, angle of repose, etc.). The model predicted wet granulation process to improve the APIs properties for tablet formulation. Additionally, the model was used to predict performance of various direct compression scenarios of omeprazole and the co-processed blends at various drug loadings using single component data, applying proprietary mixing rules. Alternatively, the omeprazole pellets were prepared by multiple manufacturing steps comprising of mixing, granulation, drying and compression to formulate tablets. Time and energy consumption was determined for both wet granulation and dry compression methods.

Results: Table 1 summarizes inputs and outputs from the Developability Classification analysis of the omeprazole in the algorithm-based model. Overall, the recommendation was that conventional tablet dosage forms were appropriate. The small particle size was good for dissolution and bioavailability but is generally known to pose a problem in tablet manufacturing process. Therefore, the processability was evaluated to determine best possible methods. Figure 1 summarizes the results from the algorithm-based model processability analysis for the API. It was determined that it was not suitable for direct compression or dry granulation, due to low particle size, low powder density, poor flowability and poor tabletability. Therefore, a wet granulation was recommended to improved APIs PSD, flow, compactibility and compressibility. However, direct compression is simpler and less complex due to fewer manufacturing steps, less equipment and less electrical consumption. Values indicated that omeprazole alone cannot be processed by dry direct compression, but by blending omeprazole with the all-in-one co-processed excipient it could be successfully tableted by dry direct compression. Table 2 illustrates the time and energy that are required for blending, wet-granulation, drying, and compression of omeprazole as compared to dry direct compression after mixing with Kollitab^TM DC 87L.

Conclusion: This study demonstrated that there are two ways that product developers can improve sustainability of solid oral tablet formulations: By using existing digital tools to reduce initial lab trials and by using co-processed excipients that mitigate the use of wet granulation and other high-energy-consuming processes. Powered by established algorithms and connectivity to public data sources (i.e. PubChem), the algorithm-based model could be used to determine the developability classification for omeprazole with a minimum of material properties measured in the lab in only a few minutes. The omeprazole in this study was classified as DCS IIa and dissolution limited. Due to its small particle size dissolution was not predicted to be a problem. The next step was to determine the recommended processing for tablet production. The model predicted wet granulation. With sustainability targets driving toward the simplest processing scenarios, dry direct compression was a better option. Options for dry direct compression could be tested in the Powder Blend Processability application including a formulation which contained only omeprazole and the all-in-one co-processed excipient (20:80). The co-processed excipient contains all of the necessary functionality for ideal tablet characteristics and performance (e.g., binder, lubricant, disintegrant, glidant, etc.). Due to its particle size and spherical morphology, the co-processed excipient was also predicted to be able to improve the flowability and processability of omeprazole, as seen in Figure 1, so dry direct compression became feasible for omeprazole. Based on processing data from studies with omeprazole, comparisons were made between time and energy consumed by wet-granulation vs dry direct compression with the co-processed excipient. Figure 2 shows the differences with 6.77 kWH for wet granulation and related steps compared to 1.45 kWH for dry direct compression ( >4.5 times reduction in the energy consumption). By using readily available digital tools and co-processed excipients it was possible to significantly reduce power consumption (and the related Scope II carbon emissions), product development lab trials, time and labor to develop omeprazole tablets.

Table 1. Developability classification of omeprazole as calculated by an algorithm-based application, including inputs from API lab characterization, chemical attributes pulled from PubChem and outputs from the algorithm.

Figure 1. Comparison of processability of omeprazole (grey line) vs omeprazole blended with an all-in-one co-processed excipient (KollitabTM DC 87L).

Figure 2. Comparison of steps, duration and power consumption during wet granulation and tableting versus blending with all-in-one co-processed excipient (KollitabTM DC 87L) and dry direct compression.