(231c) Development of Apap Tablets in a 3D Mold Using Drops of Dissolved Excipients

Excipients are a well-known asset in pharmaceutical tablet formation. Most excipients function as a binder or carrier for an active pharmaceutical ingredients (API) during the granulation process. Some excipients serve multiple roles such as coatings or taste improvement. However, it is important to investigate the individual influences and attributes of excipients prior to investigating process variables. The knowledge derived from such a study enables better formulation design with an overall goal of reducing production costs and improving tablet performance. Natural excipients are useful as the materials are normally hydrophilic and have shown great promise. It is essential to characterize natural excipients for tablet properties to minimize potential issues during processing. Natural excipient will vary in ability and performance. In this study, excipients are in two categories – natural gums and sugars/sweeteners. The performance of these excipients are compared to the performance of two commonly effective and synthetic excipients, polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG). Likewise, the compatibility of the API and excipient should be investigated. The objective of this research is to determine the feasibility of adopting select natural gums and sweeteners as safe and economic replacement excipients based on characterization and performance testing.

Tablet formation occurred in molds that were created using a Flash-Forge 3D printer. Paracetamol (APAP) in powder form was chosen as the API for this study. Dry APAP powder and liquid binder solution at various saturation levels were placed into holes created on each mold. The liquid binder solutions were created by dissolving the powder excipient into deionized water. The molds were placed in a drying oven for 24 hours. The weight of each granule was recorded with size and shape determined using image analysis software. Tablet performance was determined using friability testing, compression testing, dissolution testing, and disintegration testing. Further analysis included X-ray diffraction and ATR FTIR.

The purpose of using a 3D printed mold was to control the overall shape of the tablets and to ensure each tablet contain the same amount of APAP. Various mold designs were investigated to reduce moisture in the tablets and increase heat transfer within the molds. The designs improved the previous method of using a powder APAP bed. Overall, the type of excipient influenced tablet performance during each testing method. The saturation level of the liquid binder affected both friability and disintegration. The new 3D-mold method produced tablets of common size, shape, and weight which was an improvement from previous research. The compression testing showed that the synthetic excipients are able to withstand a larger stress than the natural excipients. Rapid dissolution kinetics (greater than 60% dissolution in 15 minutes) were noted for most of the excipients investigated. During friability testing, tablets made from pectin were completely destroyed while the other excipients had less than 10% friability. The results also showed that increasing the saturation level of the liquid binder solution will cause a decrease in the percent friability. Disintegration time varied with respect to the different excipients. Based on this study, natural excipients such as d-sorbitol have the potential to replace synthetic binders as pharmaceutical excipients.