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Recently, various innovative technologies have been developed for the enhanced delivery of biologics as attractive formulation targets including polymeric micro and nanoparticles. Combined with personalized medicine, this area can offer a great opportunity for the improvement of therapeutics efficiency and the treatment outcome. Herein, a novel manufacturing method has been introduced to produce protein-loaded chitosan particles with controlled size. This method is based on an additive manufacturing technology that allows for the designing and production of personalized particulate based therapeutic formulations with a precise control over the shape, size, and potentially the geometry. Sprayed multi adsorbed-droplet reposing technology (SMART) consists of the high-pressure extrusion of an ink with a well determined composition using a pneumatic 3D bioprinting approach and flash freezing the extrudate at the printing bed, optionally followed by freeze drying. In the present study, we attempted to manufacture trypsin-loaded chitosan particles using SMART. The ink and products were thoroughly characterized by dynamic light scattering, rheometer, Scanning Electron Microscopy (SEM), and Fourier Transform Infra-Red (FTIR) and Circular Dichroism (CD) spectroscopy. These characterizations confirmed the shape morphology as well as the protein integrity over the process. Further, the effect of various factors on the production were investigated. Our results showed that the concentration of the carrier, chitosan, and the lyoprotectant concentration as well as the extrusion pressure have a significant effect on the particle size. According to CD spectra, SMART ensured Trypsin's secondary structure remained intact regardless of the ink composition and pressure. However, our study revealed that the presence of 5% (w/v) lyoprotectant is essential to maintain the trypsin's proteolytic activity. This study demonstrates, for the first time, the viability of SMART as a single-step efficient process to produce biologics-based stable formulations with a precise control over the particulate morphology which can further be expanded across numerous therapeutic modalities including vaccines and cell/gene therapies. [ABSTRACT FROM AUTHOR]

Conventional oral dosage forms may not always be optimal especially for those patients suffering from dysphasia or difficulty swallowing. Development of suitable oral thin films (OTFs), therefore, can be an excellent alternative to conventional dosage forms for these patient groups. Hence, the main objective of the current investigation is to develop oral thin film (OTF) formulations using novel solvent-free approaches, including additive manufacturing (AM), hot-melt extrusion, and melt casting. AM, popularly recognized as 3D printing, has been widely utilized for on-demand and personalized formulation development in the pharmaceutical industry. Additionally, in general active pharmaceutical ingredients (APIs) are dissolved or dispersed in polymeric matrices to form amorphous solid dispersions (ASDs). In this study, acetaminophen (APAP) was selected as the model drug, and Klucel™ hydroxypropyl cellulose (HPC) E5 and Soluplus® were used as carrier matrices to form the OTFs. Amorphous OTFs were successfully manufactured by hot-melt extrusion and 3D printing technologies followed by comprehensive studies on the physico-chemical properties of the drug and developed OTFs. Advanced physico-chemical characterizations revealed the presence of amorphous drug in both HME and 3D printed films whereas some crystalline traces were visible in solvent and melt cast films. Moreover, advanced surface analysis conducted by Raman mapping confirmed a more homogenous distribution of amorphous drugs in 3D printed films compared to those prepared by other methods. A series of mathematical models were also used to describe drug release mechanisms from the developed OTFs. Moreover, the in vitro dissolution studies of the 3D printed films demonstrated an improved drug release performance compared to the melt cast or extruded films. This study suggested that HME combined with 3D printing can potentially improve the physical properties of formulations and produce OTFs with preferred qualities such as faster dissolution rate of drugs. [ABSTRACT FROM AUTHOR]