The effect of manufacturing method on polymer stability and drug release from PEO matrix tablets: A comparison among three methods; physical mixture, hot melt extrusion, and 3D printing

Thermal 3D printing has gained substantial attention in pharmaceutical formulation, especially concerning its potential use in personalized dose delivery. The choice of a printable polymer is crucial in this technique, but it is restricted due to technical issues such as thermal stability and thermal-rheological properties of the polymers. Polyethylene oxide (PEO) is a widely used polymer in drug formulation designs, with potential application in 3D printing due to its favourable rheological properties.  However, the thermal stability of PEOs exposed to high temperatures during FDM needs to be characterized. This research focused on the characterization of two molecular weights of PEO (7M and 0.9M) under various manufacturing methods and formulation compositions. PEO was mixed with other low-viscosity polymers of hydroxypropyl cellulose (HPC) or ethyl cellulose (EC) to achieve printable formulations (PEO/HPC or PEO/EC). Tablets were manufactured by direct compression, compression of hot-melt extrudates, HME, (at 150 oC), or by FDM 3D-printing FDM (at 220 oC). Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), gel permeation chromatography (GPC), and dissolution tests and their kinetics studies were carried out. Results showed that thermal processes could reduce the crystallinity of PEO and induce some molecular weight reduction that varies depending on the Mw of PEO. As a result, dissolution efficiency (DE%) was influenced depending on the formulation composition and the method of manufacturing. For formulations containing PEO and HPC, 3D printed and HME tablets showed higher DE (>60%) compared to directly compressed tablets (DE<50%), while for those with PEO and EC, 3D printing reduced DE% to <26% compared to direct compression (~30%) and HME tablets (~50%). This was attributed to the hydrophobic nature of EC and the increased hardness of the printed tablets, preventing tablet disintegration during dissolution which outweighs the molecular weight reduction in PEO.</p

Solubility prediction of clonazepam in aqueous mixtures of ethanol, polyethylene glycol 200 and propylene glycol at 30°C

Solubility of clonazepam in aqueous binary mixtures of ethanol, polyethylene glycol 200 and propylene glycol was determined at 30°C using the shake flask method. The maximum solubility of clonazepam was observed at volume fraction of 0.90 ofethanol, whereas for aqueous mixtures of polyethylene glycol 200 and propylene glycol, the maximum values were observed in the neat cosolvents. The generated data was fitted to the Jouyban-Acree model and its constants were computed, then the back-calculated solubilities were compared with the corresponding experimental values by calculating the mean percentage deviation (MPD) in which the overall MPD for three cosolvent systems was 7.0 %. The solubility data in cosolvent + water mixtures was predicted using previously trained versions of the Jouyban-Acree model and the prediction MPDs were 13.4, 542 and 24.9 %, respectively for ethanol, polyethylene glycol 200 and propylene glycol mixtures and the overall MPD was 30.8 %

Piroxicam nanoparticles for ocular delivery: Physicochemical characterization and implementation in endotoxin-induced uveitis

To investigate the anti-inflammatory impacts of piroxicam nanosuspension, in the current investigation, piroxicam:Eudragit RS100 nanoformulations were used to control inflammatory symptoms in the rabbits with endotoxin-induced uveitis (EIU). The nanoparticles of piroxicam:Eudragit RS100 was formulated using the solvent evaporation/extraction technique. The morphological and physicochemical characteristics of nanoparticles were studied using particle size analysis, X-ray crystallography, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Drug release profiles were examined by fitting the data to the most common kinetic models. Selected nanosuspensions were used to assess the anti-inflammatory impacts of piroxicam nanoparticles in the rabbits with EIU. The major symptoms of EIU (i.e. inflammation and leukocytes numbers in the aqueous humor) were examined. All the prepared piroxicam formulations using Eudragit RS100 resulted in a nano-range size particles and displayed spherical smooth morphology with positively charged surface, however, the formulated particles of drug alone using same methodology failed to manifest such characteristics. The Eudragit RS100 containing nanoparticles displayed lower crystallinity than piroxicam with no chemical interactions between the drug and polymer molecules. Kinetically, the release profiles of piroxicam from nanoparticles appeared to fit best with the Weibull model and diffusion was the superior phenomenon. The in vivo examinations revealed that the inflammation can be inhibited by the drug:polymer nanosuspension more significantly than the microsuspension of drug alone in the rabbits with EIU. Upon these findings, we propose that the piroxicam:Eudragit RS100 nanosuspensions may be considered as an improved ocular delivery system for locally inhibition of inflammation