Drop printing of pharmaceuticals: Effect of molecular weight on PEG coated‐naproxen/PEG 3350 solid dispersions

Abstract

Solid dispersions have been used to enhance the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). However, the solid state phase, compositional uniformity, and scale-up problems are issues that need to be addressed. To allow for highly controllable products, the Drop Printing (DP) technique can provide precise dosages and predictable compositional uniformity of APIs in two/three dimensional structures. In this study, DP was used to prepare naproxen (NAP)/polyethylene glycol 3350 (PEG3350) solid dispersions with PEG coatings of different molecular weights (MW). A comparison of moisture-accelerated crystallization inhibition by different PEG coatings was assessed. Scanning electron microscopy (SEM), second harmonic generation (SHG) microscopy, and differential scanning calorimetry (DSC) analysis were performed to characterize the morphology and quantify the apparent crystallinity of NAP within the solid dispersions. Thermogravimetric analysis (TGA) was employed to measure the water content within each sample. The results suggest that the moisture-accelerated crystallization inhibition capability of the PEG coatings increased with increasing MW of the PEG coating. Besides, to demonstrate the flexibility of DP technology on manufacturing formulation, multilayer tablets with different PEG serving as barrier layers were also constructed, and their dissolution behavior was examined. By applying DP and appropriate materials, it is possible to design various carrier devices used to control the release dynamics of the API.

High‐Throughput Miniaturized Screening of Nanoparticle Formation via Inkjet Printing

“…Different materials have been printed by inkjet systems spanning from cells to genes or proteins to polymers to nanomaterials and some pharmaceutical formulations …”

“…Different materials have been printed by inkjet systems spanning from cells [10] to genes [11,12] or proteins [13] to polymers [14] to nanomaterials and some pharmaceutical formulations. [15][16][17] In a singular and pioneering work by Hauschild et al, [15] unilamellar nanovesicles were printed from a conventional desktop inkjet printer, using ethanol solutions of both lipidlike and amphiphilic copolymers, resulting in NPs with reproducible sizes ranging between 50 and 220 nm. In the same work, it was also shown that fluorescein-loaded vesicles with narrow-size distributions could be directly produced via the printing method.…”

3D printing of tablets using inkjet with UV photoinitiation

“…Varan et al has investigated the prolonged release behaviour of inkjet printed paxitaxel in a cyclodextrin inclusion complex and cidofovir encapsulated in polycaprolactone nanoparticles dispensed onto bioadhesive films . Low melting temperature PEG/naproxen mixtures Zhu et al, 2013;Hsu et al, 2015) have been reported for melt based inkjet applications in which crystalline domains of the drug could be affected by PEG coatings (Hsu et al, 2015), or controlled melt cooling . Lee et al successfully produced paxlitaxel loaded poly(lactic-co-glycolic acid) microparticles with various geometries (honeycombs, grids, rings and circles) and observed that the drug release rate was dependant on the surface area of the microparticles (Lee et al, 2012).…”

3D Printing of Pharmaceutical Application: Drug Screening and Drug Delivery

“…The device achieved zero-order drug release kinetics of antiepileptic drugs, improved patient compliance, achieved effective therapeutic doses, and minimized side effects. In addition, Hsu et al confirmed that the 3D printing technology could produce highly reliable solid dispersions with precise dosage control of active pharmaceutical ingredients [ 181 ]. The study used PEG with an excellent biodegradation profile and naproxen, an anti-inflammatory agent, as a model drug and successfully developed a drug delivery system with uniform composition and sustained-release kinetics.…”