(W1230-09-49) Optimization of Ocular Mini Tablet Formulations: A Comparative Study of 3D FDM Printing and Vacuum Compression Molding Methods for Sustained Drug Release

Purpose: Topical corticosteroids, like hydrocortisone, are vital for treating ocular conditions, but their effectiveness depends on sustained release, especially in post-operative care. While existing products meet some needs, there's a demand for sustained formulations to improve patient outcomes. The study aims to examine the predictive capacities of micro-scale Vacuum Compression Molding (VCM) to enhance the prediction of the in-vitro release behavior in 3D printed tablet via FDM for corticosteroid-based ocular therapies via design of experiment (DoE) methodology. Through varying of ingredient concentrations, our objective is to engineer formulations capable of sustaining drug release for 24 hours while demonstrating sufficient mechanical integrity to meet therapeutic demands as shown in Fig (1).

Methods: The study focused on utilizing a Design of Experiments (DoE) approach to customize excipients, including Hydroxy propyl cellulose, Soluplus®, PEG 4500, and Eudragit® EPO, with their different percents detailed in Table 1. The optimized minitablet was designed to achieve sustained release behavior over 24 hours using JMP 16 software. In-vitro dissolution testing was conducted, and various characterization methods were employed to assess the properties of the developed formulation. Following the scaling up process using the Hot Melt Extrusion (HME) method then 3D printing using FDM, the in-vitro release of the drug from the ocular tablet prepared with FDM was evaluated to compare it with the optimized VCM tablet.

Results: The successful preparation and optimization of Hydrocortisone ocular minitablets were achieved using the VCM technique to ensure sustained release over 24 hours, employing mixture design via JMP software. Characterization of the VCM minitablets included assessing uniformity in thickness, diameter, and weight, resulting in measurements of 0.34± 0.03 mm, 7.7± 0.15 mm, and 20.8 ± 1.3 mg, respectively. Solid-state analysis was conducted using differential scanning calorimetry and X-ray powder diffraction for the optimized VCM tablet and individual polymers and drug. Additionally, swelling tests and in vitro mucoadhesive tests were performed on the optimized VCM formulation to evaluate its adhesive characteristics, revealing a mucoadhesive force of 0.28 ± 0.006 N and approximately 600% hydration within 30 minutes. Investigation into scaling up the optimized VCM formulation to Hot Melt Extrusion (HME) then printing using 3D FDM printer was conducted by comparing the in vitro drug release profiles prepared using both techniques. The results indicated that the VCM tablets released 96.7 ± 0.4% of HC within 24 hours, while the HME-prepared tablets released 88.5 ± 4.9% HC. A notable variance in the release of the two types of tablets was observed (P-value 0.0037), indicating a significant difference.

Conclusion: This study evaluated the potential of VCM technology as a screening tool for designing FDM tablets with targeted release behavior on a small scale. While the Design of Experiments (DoE) successfully optimized a VCM ocular mini tablet with the intended release duration, scaling up via HME and 3D printing with FDM did not replicate the optimized release timeframe.

Figure 1 (A) optimized mini tablet prepared by VCM, (B) minitablet prepared by FDM.

Table 1. Mixture design for the development and optimization of Hydrocortisone ocular minitablet

Figure 2. Release profiles of optimized VCM tablet and FDM tablet in 3 mL phosphate buffer 7.4. Data are presented for triplicates.