Abstract
The aim of the study was to prepare indomethacin nanocrystal-loaded, 3D-printed, fast-dissolving oral polymeric film formulations. Nanocrystals were produced by the wet pearl milling technique, and 3D printing was performed by the semi-solid extrusion method. Hydroxypropyl methyl cellulose (HPMC) was the film-forming polymer, and glycerol the plasticizer. In-depth physicochemical characterization was made, including solid-state determination, particle size and size deviation analysis, film appearance evaluation, determination of weight variation, thickness, folding endurance, drug content uniformity, and disintegration time, and drug release testing. In drug nanocrystal studies, three different stabilizers were tested. Poloxamer F68 produced the smallest and most homogeneous particles, with particle size values of 230 nm and PI values below 0.20, and was selected as a stabilizer for the drug-loaded film studies. In printing studies, the polymer concentration was first optimized with drug-free formulations. The best mechanical film properties were achieved for the films with HPMC concentrations of 2.85% (w/w) and 3.5% (w/w), and these two HPMC levels were selected for further drug-loaded film studies. Besides, in the drug-loaded film printing studies, three different drug levels were tested. With the optimum concentration, films were flexible and homogeneous, disintegrated in 1 to 2.5 min, and released the drug in 2–3 min. Drug nanocrystals remained in the nano size range in the polymer films, particle sizes being in all film formulations from 300 to 500 nm. When the 3D-printed polymer films were compared to traditional film-casted polymer films, the physicochemical behavior and pharmaceutical performance of the films were very similar. As a conclusion, 3D printing of drug nanocrystals in oral polymeric film formulations is a very promising option for the production of immediate-release improved- solubility formulations.
Highlights
Today, poor solubility creates great challenges in the drug industry, and nanosizing is an efficient and simple way to overcome the problem [1,2]
Based on the particle size and polydispersity index (PDI) results, the smallest particles with the lowest polydispersity values were obtained with Poloxamer F68 as a stabilizer, and those two nanosuspension formulations were selected for further film studies
Physicochemical and Mechanical Characterization of the Films In our earlier studies, we showed that the produced indomethacin nanocrystal formulations, used in this study, are crystalline after the nanomilling [24]; in this study, only the printed formulations were analyzed
Summary
Poor solubility creates great challenges in the drug industry, and nanosizing is an efficient and simple way to overcome the problem [1,2]. Nanosizing is just the first step in the manipulation of raw drug material. Oral polymeric films ( named oral thin films or oral strips) are a recent drug delivery form, which has high patient compliance, because they can be administered without water [5]. They can be produced, for example, by solvent casting [4], hot-melt extrusion [6], electrospinning [7], or 3D printing techniques [8], and for nanocrystal-based drug delivery systems, nanosuspensions can be used as such by only mixing the suspension with a polymeric excipient solution
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
