(W1030-01-06) Felodipine Solubility Enhancement via Polymeric-Lipid Extrusion 3D Printing; Development and Stability

Purpose: The purpose of this study is to enhance the bioavailability of felodipine by increasing its solubility in a lipid based formulation, along with stability determination of developed formulations.

Methods: Five different printable formulations were prepared with various ratios of a lipid excipient and API (Felodipine) by melting the excipients above their melting point and mixing with felodipine. The formulations were allowed to solidify at room temperature before printing. Tablets intended to deliver modified release were printed via extrusion at 50° C, under a pressure of 8 kPa, at a rate of 5 mm/sec Differential scanning calorimetry and X-ray powder diffraction were performed to test process and material suitability. Dissolution testing was performed according to the USP method. Scanning Electron Microscopy / Energy Dispersive Spectroscopy was used along with previously mentioned analytical techniques to study the effect of aging and accelerated stability conditions on the samples.

Results: DSC and XRPD showed no major interactions between felodipine and the excipients and were comparable to literature. After one day storage at 37 ± 0.5 °C, and 75% RH, DSC showed a new peak at around 110° C indicating an instability in the system. SEM images showed signs of drug crystallization within the aged samples as confirmed by localised elemental analysis. In contrast, FT-IR and XRPD showed no significant changes under accelerated conditions. As crystals are evident on the sample surfaces the amount is suggested to be below the detectable limit of XRPD (approx. at best >1% w/w), this would suggest that there is no significant bulk crystallisation, it only localised to the surface. The rate of drug release increased in all tested samples compared to the pure drug controls, however, the amount of drug released decreased with aging under accelerated conditions, consistent with some of the drug becoming crystalline and hence less soluble.

Conclusion: 3D printing of polymeric lipid solid oral tablet was successfully accomplished. Analytical testing confirmed the applicability of printing along with compatibility of employed materials. Release study showed an increase in effective felodipine solubility, although this decreased with time due to partial surface recrystallisation of the drug. In our study, we have presented the novel use of lipidic materials in a 3D printing as an approach for augmentation of solubility of a poorly water-soluble drug. Although further work on stabilization of the formulation is required this represents an alternative approach to the traditional use of polymeric based printable formulations.

Acknowledgements: Saudi Cultural Bureau for PhD scholarship. Quotient Science for advising and further using facilities.

Formulation content

Felodipine release profiles from fresh, aged, and accelerated conditions prints

SEM/EDS image of Aged sample