PEO hot melt extrudates for controlled drug delivery: Importance of the type of drug and loading

Abstract

A variety of poly(ethylene oxide) (PEO)-based matrix tablets loaded with theophylline, ibuprofen or metoprolol tartrate was prepared via hot melt extrusion. The initial drug loading was varied from 10 to 60 %, the PEO polymer molecular weight from 300 to 7,000 kDa. The extrudates were characterized before and after exposure to phosphate buffer pH 7.4 at 37 °C using optical and scanning electron microscopy, X-ray diffraction analysis and drug release measurements. In the case of metoprolol tartrate, the resulting drug release rates monotonically increased with increasing initial drug loading, irrespective of the PEO grade. This can be attributed to an "increased porosity effect" upon drug leaching, resulting in less hindrance for subsequent drug release. However, in the case of theophylline and ibuprofen, also "limited drug solubility effects" played a role and were even dominant in 7,000 kDa PEO-based extrudates:Upon water penetration into the system, not all of the drug was dissolved. Dissolved and nondissolved drug co-existed. Importantly, only dissolved drug is available for diffusion. Thus, increasing the initial drug content did not increase the concentration gradients of dissolved drug (and the absolute drug release rates in the absence of porosity effects), but increased the 100 % reference values. Interestingly, in 300 kDa PEO-based extrudates, "increased porosity effects" dominated for all drugs, and the relative release rates always increased with increasing drug loading. At 1,000 and 7,000 kDa, the resulting released rate increased or decreased with increasing drug loading, depending of the type of drug.

Cyclodextrin Stabilized Freeze-Dried Silica/Chitosan Nanoparticles for Improved Terconazole Ocular Bioavailability

“…Changing the cryoprotectant type from MβCD to HPβCD causes a significant decrease in both Q 2 ( Figure 2 b) and Q 6 ( Figure 2 d) values. Referring to the nanoparticle DL value results and by relating the associated decrease in DL with the increasing the cryoprotectant concentration, it could be deduced that the driving force for the drug to be released would decrease, resulting in a more sustained release pattern for the drug, which is in accordance to Fick’s first law [ 69 , 70 ]. Similar explanations were reported when changing the cryoprotectant type.…”

Impact of process stress on protein stability in highly-loaded solid protein/PEG formulations from small-scale melt extrusion

“…Lysozyme, bovine serum albumin (BSA), and human insulin were chosen as (model) proteins and peptide, respectively and were embedded in polyethylene glycol (PEG) 20,000-matrices. PEG is a hydrophilic polymer and next to an increasing half-life of the protein also used as potential protein stabilizer by addition of PEG-chains to proteins (PEG-ylation) or co-processing with PEG (Al-Azzam et al, 2002 ; Cantin et al, 2021 ; Chen et al, 2021a ). Furthermore, several studies suggest that long PEG-chains (e.g., PEG 20,000) can stabilize proteins by interacting with the protein surface or by the formation of the excluded volume effect to decelerate the unfolding rate of the protein ( Chao et al, 2014 ; Pandey et al, 2013 ).…”

“…Furthermore, several studies suggest that long PEG-chains (e.g., PEG 20,000) can stabilize proteins by interacting with the protein surface or by the formation of the excluded volume effect to decelerate the unfolding rate of the protein ( Chao et al, 2014 ; Pandey et al, 2013 ). Furthermore, higher molecular weight PEG (also known as polyethylene oxide (PEO) depending on its molecular weight) offers an potential as matrix polymer for controlled release dosage forms and is commercially available in a broad variety of PEO grades and different molecular weights (e.g., 100,000, 300,000, 1,000,000) ( Cantin et al, 2021 ). We selected PEG 20,000 as model polymer due to its (i) low melting temperature (∼60 °C, depending on the chain-length), (ii) hydrophilicity and (iii) potential as protein stabilizer.…”

Eudragit®: A Versatile Family of Polymers for Hot Melt Extrusion and 3D Printing Processes in Pharmaceutics

“…HME has been applied using a wide range of polymers in the production of different drug delivery systems, such as tablets [6,7], pellets [8,9], implants [10] and transdermal systems [11,12], but has been especially focused on the production of solid dispersions (SDs) of poorly water-soluble drugs [4]. However, in the last few years, its use in pharmaceutics has been boosted even more due to it being linked to 3D printing processes in the development of innovative medicines.…”