Category: Formulation and Quality
Purpose: Concerns about opioid risks in the postoperative period have spurred an increased interest in the use of nonopioid drugs for long-term pain relief. Lidocaine is an inexpensive and easy-to-access pain relief medication. The challenge is to deliver lidocaine using a sustained release formulation to overcome its short half-life, aiming to suppress prolonged postoperative pain. In this study, we designed multi-layered films that can elute lidocaine for an extended period and constructed various prototypes in a customizable and precise manner using a 3D printing technique.
Methods: Biodegradable Poly(D,L-lactide/glycolide) (PLGA) polymers (PLA:PGA ratio 50:50) with various average molecular weight (12,000, low; 20,000, medium; and 150,000, high) were mixed with lidocaine in the solvent. The mixture was then extruded by using a Hyrel system standard resolution 3D printer. Components of the 3D printer included a cold flow printing head, a glass stage, a metal nozzle (0.84 mm in diameter, 18 gauge needle), and a sterile disposable 5 mL syringe. The mixture was extruded from the syringe and deposited on the glass stage under vacuum. The layers of the PLGA films were stacked under the linear motion control in X, Y, and Z axes. After printing each layer, printing was halted for 10 min to allow the solvent to evaporate and film to dry. The diameter, thicknesses, and weight of the printed film rounds and the content level of lidocaine in each layer were recorded to evaluate reliability of the 3D printing technology. Lidocaine incorporated in each film was extracted and quantified using High Performance Liquid Chromatography (3 mm x 100 mm C18 column, mobile phase: 20% water, 70% acetonitrile, and 10% 200 mM ammonium acetate). The USP Dissolution Apparatus IV was be used to determine the dissolution rate of lidocaine from the films.
Results: We successfully 3D-printed multi-layered nanofilms (single- and triple-layered films) carrying lidocaine. The average diameter and weight were 16 ± 1.0 mm and 36 ± 3.0 mg for the single-layered films (low, medium, or high), and 17 ± 0.1 mm and 107 ± 0.0 mg for the triple-layered films (high/low/medium and high/medium/low). Each PLGA layer carried 3 mg of lidocaine. Single-layered films constructed with low or medium molecular weight PLGA demonstrated relatively more rapid onset of in vitro lidocaine release, eluting >10% lidocaine in 10 days. Single-layered films constructed with high molecular weight PLGA, and triple-layered films constructed with low, medium, and high molecular weight in the stacking orders of high/low/medium and high/medium/low showed much slower release profiles of lidocaine, eluting < 10% of lidocaine in 30 days.
Conclusion: The single- and triple-layered film rounds were successfully prepared using a commercially available 3D printer in a consistent and precise manner. We were able to build 3D-printed biodegradable films containing lidocaine that can serve a device for long-term pain relief.