LAO dosage forms (DF) can reshape the way patients take medicine. Reducing dosing frequency from daily to a weekly or monthly dose can alleviate the burden of medication compliance and challenges associated with chronic conditions. No traditional oral extended release strategies can prolong release of most small molecules beyond 24 hrs. Lyndra’s LAO DF, however, can release drugs while residing in the stomach for days to weeks. It is administered as an oral capsule that unfolds to an expanded configuration in the stomach, preventing its passage through the pylorus over the desired residence period and allows sustained drug release from a polymeric matrix. This matrix should also maintain physical integrity during this period. Lyndra’s DF is produced using traditional pharmaceutical methods including hot melt extrusion (HME) of polymer-drug suspensions. An alternative strategy for controlling drug release from LAO DFs involves complex multi-material structures, such as pores, which cannot be easily achieved with extrusion. We explored fused-deposition modeling (FDM) based 3D printing to customize polymer-drug matrix architectures. Pharmaceutical-grade thermoplastic materials were evaluated for their processibility with a FDM 3D printer. Polymer-drug formulations were 3D printed (3DP) and the drug release profile and physical properties of 3DP matrices were compared to monolithic matrices produced by HME. For hydrophobic drugs, a two-part architecture with separate drug release and physical components offers certain potential advantages and these were produced by FDM. A rapidly releasing drug-polymer matrix was formulated and non-drug containing outer structural layer or shell with pores was 3D printed. This structural layer controlled the water exposure of the drug-loaded material thereby controlling drug release. Linear release of a hydrophobic drug was achieved over 14 days with 3DP shell providing mechanical strength <b>(Fig 1)</b>. This work describes feasibility assessment and pilot development of a FDM 3DP method to produce LAO gastric residence forms with novel architectures.

Development of novel 3D printed long-acting oral (LAO) drug delivery systems

256th National Meeting (2018)

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