(W1130-11-70) Fabrication of Suppository Shells via Hot-Melt Extrusion Paired with Fused Deposition Modeling (FDM) 3D Printing Techniques

Purpose: Suppositories are solid dosage forms containing API that are either dispersed or dissolved in a suitable base, which upon melting or solubilization at physiological conditions, releases the drug for either local or systemic action[1]. Traditional suppositories are associated with issues, such as difficulty in achieving simple and precise dose volume control and drug-matrix interaction. Hollow-type (HT) suppositories address these issues and provide a very convenient preparation. HT suppositories contain a hollow space for filling with the drug in solid, liquid, or semi-solid form. The benefits of this design are controlling the dosage of the drug, allowing convenient interchangeability of the drug, and preventing any interactions between the drug and the base material[2]. In this study, novel HT suppository shells with different materials were designed and developed via HME and FDM 3D printing. And the drug release of each suppository formulation was studied.

Methods: An 11mm twin-screw extruder (Thermo Fisher Scientific, MA, USA) was fabricating filaments for 3D printing. As shown in Table 1, different formulations were investigated and separated into three stages. The HT suppository shells were designed using Blender and printed by the FDM 3D printer (Ultimaker 3). The suppository formulations were prepared by the fusion method. APAP, PEG400, and PEG6000 were mixed at a ratio of 1:2:6 and melted together in a beaker at 80 °C in a water bath until APAP was completely dispersed in PEG. Holes in the suppository shells were first sealed with tape, and the mixture was quickly pipetted into the suppository shell from the bottom. Finally, the bottom was covered with a lid, and samples were cooled and solidified in a refrigerator. The in vitro release study was carried out using a USP dissolution apparatus II in 900 mL pH 6.8 phosphate buffer, with the temperature maintained at 37 ± 0.5℃ and a paddle rotation speed set at 50 rpm.

Results: Figure 1 shows the development process of the HT suppository shell. Stage one is to investigate the effect of pore size on the release of the suppository. Three different sizes of side-hole (1mm, 2mm, 3mm) suppository shells were designed and successfully printed using PLA as the raw material. PLA is chosen because it is an insoluble polymer in water, and the pore size will not change due to polymer dissolution. The second stage is to compare the suppository shells printed with different materials. Suppository shells with a side hole diameter of 2 mm were printed using three different polymers: water-soluble rapid-release polymer-PVA, water-soluble sustained-release polymer-HPMC 15LV, and water-insoluble polymer-PLA. The third stage was to add API to the two pharmaceutical polymers (PVA and HPMC HME 15LV) in the second stage to develop the novel suppository. Figure 2 shows the dissolution profiles of all stages of suppositories. In stage one, the drug release becomes faster as the pore size increases. In stage two, the order of drug release speed is PVA type 2 > PLA type 2 > HPMC 15LV type 2. In stage three, both types of suppositories exhibit an initial rapid release followed by a slowing down until complete release.

Conclusion: In this study, different type of HT suppository shells was successfully formulated and produced using HME and FDM 3D printer. The utilization of 3D printing technology has the potential to facilitate personalized medicine by enabling the customization of drug compositions and designs.

References: [1] S. Hua, Physiological and pharmaceutical considerations for rectal drug formulations, Front. Pharmacol. 10 (2019) 1–16. https://doi.org/10.3389/fphar.2019.01196.
[2] H. Shiohira, M. Fujii, N. Koizumi, M. Kondoh, Y. Watanabe, Novel chronotherapeutic rectal aminophylline delivery system for therapy of asthma, Int. J. Pharm. 379 (2009) 119–124. https://doi.org/10.1016/j.ijpharm.2009.06.017.

Table1. Formulation composition and operation parameter of filaments.

Figure 1: The development process of HT suppository shell.

Figure 2. The dissolution profiles for all stages of suppositories.