Electrostatic powder deposition as a dry powder process to prepare orodispersible films
Orodispersible films (ODFs) are an advantageous dosage form, particularly for pediatric and geriatric populations, due to their ease of administration. ODFs are predominantly manufactured by solvent casting using aqueous or organic solvents. However, this process may be limited by long drying times for aqueous systems, required solvent handling capabilities and residual solvent testing for organic solvents, or due to moisture or solvent sensitive active pharmaceutical ingredients (API). Additionally, solvent casting can produce non-uniform doses due to API aggregation in solution or during drying. More recently, electrostatic powder coating has been adapted as a dry powder process for coating pharmaceutical dosage forms, such as tablets and pellets. Electrostatic powder coating is advantageous as it eliminates the need for solvents and exhibits greater transfer efficiencies than non-electrostatic dry powder coating. In this work, this technology was further modified to utilize electrostatic powder deposition (ESPD) as a dry powder process to prepare ODFs. Low molecular weight polyethylene oxide (PEO) was investigated as the film-forming polymer for use with ESPD. The influence of processing parameters, such as charging voltage, curing conditions, and substrate roughness, on PEO deposition behavior and film formation were investigated. The deposition behavior of PEO was significantly influenced by the environmental humidity during processing due to its impact on the particle resistivity. The PEO films prepared by ESPD exhibited favorable mechanical properties, a low degree of adhesion to the substrate, and rapid disintegration. Drug-containing films were prepared using physical mixtures and composite particles of acetaminophen (APAP) and PEO. Films prepared using a physical mixture exhibited significantly higher drug content variability. The active films exhibited favorable mechanical properties due to the plasticizing effect of APAP on PEO. Additionally, the films exhibited rapid drug release in vitro, with greater than 85% drug release by two minutes. Films with increasing drug load were prepared using ESPD utilizing both physical mixtures and composite particles of benzocaine (BNZ) and PEO. Films prepared using physical mixtures were superpotent due to preferential deposition of the charged BNZ particles during ESPD. The complex viscosity profile of the composite particles were shown to decrease with increasing drug loading, enabling lower cure temperatures for film formation. Films produced using the composite particles exhibited low adhesion to the substrate and rapid in vitro drug release. However, the composite particles of the highest drug load showed greater crystalline BNZ content than the lower drug loads, resulting in a decrease in its mechanical properties, as well as a slightly reduced dissolution rate. Ultimately, this body of work demonstrated that ESPD could be utilized as a solvent-free process to prepare orodispersible films with favorable mechanical and drug release properties. Additionally, the use of composite particles has been shown to be advantageous to produce particles with favorable electrical properties, ensure film drug content uniformity, and enable reduced cure temperatures.