Category: Formulation and Quality
Purpose: Three-dimensional (3D) printing provides an alternative approach to develop an Orodispersible film. Fused Deposition Modeling (FDM), one of the most popular 3D printing technique, in combination with acid degradable substance like Lansoprazole, seems to be extra advantageous in terms of dissolution profile. The purpose of this study was to develop a 3D printed delayed-release film loaded with Lansoprazole drug.
Methods: The spray drying technique was used to prepare the Enteric Polymer-based microparticles of Lansoprazole. Eudragit® L100 and Eudragit® S100 were selected as an enteric polymer for initial characterization of drug-loaded microparticles. Briefly, Enteric polymer was added into the water, and the pH was adjusted to 9.0 using 1N NaOH solution. Lansoprazole was added and dispersed into this solution. The remaining amount of water was added into this solution to facilitate Spray drying. The solution was spray dried at 5ml/min feed rate and 140°C inlet temperature. The spray-dried particle was then washed with Acetonitrile and dried at 35°C under vacuum oven. These microparticles prepared were characterized for their Entrapment Efficiency, Gastric Resistance, Particle Size, Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), and X-Ray Diffraction (XRD).
Affinisol™ HPMC 15LV, PolyOx™ N10, and Parteck® MXP (PVA) were selected as film-forming agents. The dried microparticles were mixed with each of this polymer in the ratio of 1:1 separately in a closed plastic container using V-Blender at 15RPM for 20 mins. These powder blends were then extruded using Hot Melt Extrusion. The hot-melt extruded filaments were coiled, stored in sealed zip lock bags, and subsequently used as feedstock material for the FDM 3D printing. The 3D Printed films were then characterized by Mechanical Strength and Disintegration time.
Based on the result, the dried microparticles was then mixed with PolyOx™ N10 polymer in different Polymer: Drug Microparticles ratio of 1:0.5, 1:1, and 1:1.5. This polymer blend was extruded to prepare the filament using Hot Melt Extrusion at 55°C (Zone 1), 65°C (Zone 2), 65°C (Zone 3) and 40 RPM screw speed and this filament were used for 3D printer.
The film was designed on the Tinkercad website platform and sliced using PrusaSlicer software. The 3D Printing was performed using Prusa i3 MK3 FDM desktop printer which has an extruder with E3D v6 HotEnd and 0.4mm nozzle. The printing parameters were set as follows: Nozzle temperature, 125°C; Bed temperature, 40°C; Layer height, 0.10 mm; %Infill, 90%. The dimensions and weights of the 3D printed (3DP) films were then measured. The film was then characterized by Disintegration, Tensile strength, Dissolution, DSC, FTIR, and XRD study.
Results: The drug-loaded microparticles coated with Eudragit® S100 enteric polymer with the Drug: Polymer ratio of 1:5 shows better Entrapment Efficiency and better Gastric Resistance than the Eudragit L100 (Table 1). The film printed from the filaments containing Affinisol™ HPMC 15LV and Parteck® MXP had higher tensile strength and higher disintegration time respectively compared to the film prepared from PolyOx™ N10 (Table 2). The significant advantage of PolyOx™ N10 film was low disintegration time and enough mechanical strength. There was no significant difference in mechanical strength of any of the film (Range: 0.51 - 0.82 MPa). Hence, PolyOx™ N10 polymer was used for further study. The filament with a 1:1.5 ratio of Polymer: Drug loaded microparticles was not strong enough to print using the 3D printer. The 3D printed film with a 1:1 ratio of Polymer: Drug microparticles had lower disintegration time compared to the film with a 1:0.5 ratio (Table 3). Hence, 1:1 ratio of Polymer: Drug microparticles was selected as the final formulation. The dissolution profile shows that 3D printed film containing Lansoprazole had < 10% drug release in acidic media (0.1N HCl) and more than 80% drug release in the next 20 mins in pH 7.4 Phosphate buffer media (Figure 1). The DSC thermograms, X-Ray Diffraction, and FTIR study show that there was no drug-polymer interaction in the formulation, and the drug was miscible with the excipients in the formulation (Figure 2).
Conclusion: In this study, the delayed-release orodispersible film loaded with Lansoprazole drug were successfully developed. Eudragit® S100 as enteric polymer and PolyOx™ N10 as a film-forming agent were successfully used to prepare the orodispersible film. The 3D structure design is effective and efficient for optimizing delayed drug release. The 3D printed film had enough mechanical strength and optimum disintegration time to obtain the required dissolution profile as the delayed-release orodispersible film.