Hot Melt Extrusion (HME), also known as Melt Extrusion technique, refers to a technology in which drugs and carrier excipients are uniformly mixed in a molten state and extruded with a certain pressure, speed and shape. The technology enables the drug to be dispersed in the carrier in molecular, amorphous or metastable forms, which can improve the solubility and bioavailability of insoluble drugs. It is a new formulation technology developed rapidly in recent years, showing advantages in preparing sustained and controlled release formulations and in drug delivery system with low cost, simple process, better reproducibility and high production efficiency, so that it has broad development prospects in the field of pharmaceutical R&D.
1. Principle and characteristics of HME
In preparing HME, the drug is first premixed with a thermoplastic polymeric carrier and other excipients and then filled in a single or double screw extruder, where the rotating screw drives the physical mixture for further extrusion while the extruder interlayer heats it at high temperature. The drug and the excipients are favorably compatible under the strong heat power and shearing force with transforming from a multi-phase state at the inlet to a single-phase state at the outlet and extruding through the outlet die hole. The extruded intermediates can be prepared into various solid formulations by post-processing, including tablets, capsules, membranes, pellet or powder form of prescriptions, granules and others which can be widely applied in producing preparations such as improving the bioavailability of insoluble drugs, taste masking and obtaining controlled drug release.
Compared with traditional formulation technology, the HME has the advantages of integrating various unit operations (solid delivery, material melting, shear mixing, melt mass delivery, extrusion and others), facilitating industrial production and solvent-free residue, etc. It is especially suitable for wet-sensitive drugs, by selecting different carriers to increase drug solubility and bioavailability, sustained and controlled release, enteric dissolution or taste masking effects, and can be made into many preparations such as capsules, tablets, micro-pills, implants for oral, transdermal, mucosal and implantable drug delivery in line with different requirements.
2. Application of HME in drug delivery system
2.1 Improve the solubility and bioavailability of drugs
Solid dispersion technology has prominent results in improving drug solubility and is considered to be one of the most promising technologies. HME is widely applied in the preparation of solid dispersions. With HME, drugs and carrier materials are mixed in a certain ratio, then become molten under slow heat and solidified by rapid stirring under quenching to obtain solid dispersions. It is a simple and economical method that can highly increase the drug solubility and improve the dissolution effect of insoluble drugs, improving the bioavailability; Solvents may be not utilized in the preparation. Possible solvent-related stability risks in formulation storage are avoided as no residual solvents are left.
2.2 Sustained and controlled release formulations
Sustained/controlled release drug delivery system is always a topical issue in drug R&D, which is characterized by low toxic and side effects and smooth plasma-drug concentration. Many methods are available for the preparation of sustained release formulations, and since hot melt extrudates are featured with high density and low porosity, it is possible to prepare the sustained/controlled release drug delivery system with a high drug loading capacity. The thermoplastic carrier material for sustained and controlled release is extruded with water-soluble drug by hot melt to reduce the dissolution rate, and the resulting extrudate can be sheared or pressed into suitable formulations. Polyoxyethylene matrix sustained release tablets of chlorpheniramine were prepared by direct powder compression and hot melt extrusion respectively with polyethylene oxide as drug carrier and PEG 3350 as plasticizer. Compared with the direct compression process of powder, the strong shearing mixing of the screw in the hot melt extrusion reduces the porosity, decreases the pore size and increase...
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