Development and Characterization of Sustained-Released Donepezil Hydrochloride Solid Dispersions Using Hot Melt Extrusion Technology

Abstract

The aim of this work was to develop the sustained release formulation of donepezil hydrochloride (DH) using the hot-melt extruded solid dispersion technique via the rational screening of hydrophobic carriers. Hydrophobic carriers with different physicochemical properties such as pH-independent swellability, low-permeability (Eudragit® RS PO (E-RS)), pH-independent non-swellability (ethyl cellulose N7 (EC-N7)), and the presence of lipids (Compritol® 888 ATO (C-888)) with or without pore-forming agents were used to achieve the sustained release profile of DH. Mannitol (MNT) was chosen as the temporary pore-forming agent. The thermal analysis showed that both the drug and C-888 preserved their crystallinity within a solid dispersion. During a dissolution test, MNT could generate pores, and the drug release rate was proportionally correlated to the MNT content. Tailoring of the ratio of C-888 and MNT in the formulations along with an appropriate extrusion temperature profile resulted in the modified release of DH, and a preferable release pattern was obtained under these conditions. C-888 was chosen for the further investigations to obtain tablets with a high integrity. The optimized tablets were compared to the marketed formulation of Aricept® in terms of drug release profiles. The optimized formulation showed the stable and sustained release behavior of extended release profile, which was close to the release behavior of Aricept® with good tablet characteristics. It was concluded that the hot-melt extrusion technique can be utilized for the manufacturing of DH sustained release tablets with improved tablet integrity and characteristics by co-processing the tablet excipient with DH/C-888.

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

“…For this purpose, ERS has been a good candidate, as it is a hydrophobic and insoluble polymer. Alshetaili et al (2021) produced SDs with ERS to sustain the release of donepezil hydrochloride and, consequently, to avoid the side effects of its burst release. The physical interaction between the polymer and drug during the HME process (at 150 • C) was able to amorphise the drug, which improved its solubility, promoting a faster drug release in the first hour (about 20%), and a sustained release in the following 10 h [76].…”

“…Alshetaili et al (2021) produced SDs with ERS to sustain the release of donepezil hydrochloride and, consequently, to avoid the side effects of its burst release. The physical interaction between the polymer and drug during the HME process (at 150 • C) was able to amorphise the drug, which improved its solubility, promoting a faster drug release in the first hour (about 20%), and a sustained release in the following 10 h [76]. In this specific case, the burst release was not suitable due to the drug's characteristics, but ERS can be a good polymer candidate for drugs in which a burst release followed by a slow release is desirable.…”

Preparation and in vitro evaluation of hot-melt extruded pectin-based pellets containing ketoprofen for colon targeting

“…The solvent-free hot-melt extrusion (HME) technology has gained much interest in the pharmaceutical field because of its continuous manufacturing ability. As a result, HME technology has been established for almost all routes of administration, including oral ( Alshetaili et al, 2021 ), ocular ( Khan et al, 2022 ), dermal, and parenteral formulations ( Alzahrani et al, 2022a ). Moreover, HME is a promising tool for producing high drug-load pellets in minimal steps by coupling HME with a die-surface cutting pelletizer, thus, offering a continuous pellet manufacturing process ( Treffer et al, 2014 ; Vo et al, 2020 ).…”

Preparation of Solid Dispersion of Polygonum Cuspidatum Extract by Hot Melt Extrusion to Enhance Oral Bioavailability of Resveratrol

“…Solid dispersion (SD) is a drug delivery system formed by converting poorly soluble active pharmaceutical ingredients into an amorphous state in a suitable carrier. Due to the high dispersion of insoluble drugs in SD, SD plays a unique role in the following aspects: improving the solubility and oral bioavailability of insoluble drugs [ 21 ], delaying the release time of drugs [ 22 ], controlling the release position of drugs in the body [ 23 ], and so on. Among the numerous preparation methods of SD, hot melt extrusion (HME) is a promising solvent-free continuous process and is suitable for pharmaceutical industrial production, which has attracted a great deal of attention in the pharmaceutical industry.…”