Melt extrusion: from process to drug delivery technology

Interest in hot-melt extrusion techniques for pharmaceutical applications is growing rapidly with well over 100 papers published in the pharmaceutical scientific literature in the last 12 years. Hot-melt extrusion (HME) has been a widely applied technique in the plastics industry and has been demonstrated recently to be a viable method to prepare several types of dosage forms and drug delivery systems. Hot-melt extruded dosage forms are complex mixtures of active medicaments, functional excipients, and processing aids. HME also offers several advantages over traditional pharmaceutical processing techniques including the absence of solvents, few processing steps, continuous operation, and the possibility of the formation of solid dispersions and improved bioavailability. This article, Part I, reviews the pharmaceutical applications of hot-melt extrusion, including equipment, principles of operation, and process technology. The raw materials processed using this technique are also detailed and the physicochemical properties of the resultant dosage forms are described. Part II of this review will focus on various applications of HME in drug delivery such as granules, pellets, immediate and modified release tablets, transmucosal and transdermal systems, and implants.

Pharmaceutical Applications of Hot-Melt Extrusion: Part I

Objectives With poorly soluble drug candidates emerging in the drug discovery pipeline, the importance of the solid dispersion formulation approach is increasing. This strategy includes complete removal of drug crystallinity, and molecular dispersion of the poorly soluble compound in a hydrophilic polymeric carrier. The potential of this technique to increase oral absorption and hence bioavailability is enormous. Nevertheless, some issues have to be considered regarding thermodynamic instability, as well in supersaturated solutions that are formed upon dissolution as in the solid state. Key findings After a brief discussion on the historical background of solid dispersions and their current role in formulation, an overview will be given on the physical chemistry and stability of glass solutions as they form supersaturated solutions, and during their shelf life. Conclusions Thorough understanding of these aspects will elicit conscious evaluation of carrier properties and eventually facilitate rational excipient selection. Thus, full exploitation of the solid dispersion strategy may provide an appropriate answer to drug attrition due to low aqueous solubility in later stages of development.

https://www.onlinelibrary.wiley.com/doi/epdf/10.1211/jpp.61.12.0001

Review: physical chemistry of solid dispersions

Selection of excipients for melt extrusion with two poorly water-soluble drugs by solubility parameter calculation and thermal analysis

Manufacture and characterization of mucoadhesive buccal films.

Hydroxypropylcellulose (HPC) films containing drugs or hydrophilic or hydrophobic plasticizers were prepared by a hot melt extrusion process. Polyethylene glycol 8000 (PEG 8000) 2%, triethyl citrate (TEC) 2%, acetyltributyl citrate (ATBC) 2%, and polyethylene glycol 400 (PEG 400) 1% were the plasticizing agents studied. In addition, either hydrocortisone (HC) 1% or chlorpheniramine maleate (CPM) 1% was incorporated into the films as a model drug. The physical-mechanical properties of the films that were investigated included tensile strength (TS), percentage elongation (%E), and Young's modulus (YM). Differential scanning calorimetry (DSC) was utilized to determine glass transition temperatures (Tg' s). These parameters were studied as a function of time and temperature. The glass transition temperatures initially decreased with the inclusion of the drugs and plasticizers. However, after 6 months aging, films containing PEG 400 and HC showed a marked increase in Tg. The films containing PEG 400 showed phy...

Influence of plasticizers and drugs on the physical-mechanical properties of hydroxypropylcellulose films prepared by hot melt extrusion.

Stick formulations for topical delivery of water soluble and/or water insoluble agents are disclosed. The stick formulations may contain steroids, antibiotics, antifungals, antihistamines anti inflammatories or local anesthetics. The vehicles comprise a combination of waxes and oils and a surfactant in embodiments involving water soluble agents. Methods for preparing the various stick formulations are also disclosed.

Stick formulations for topical drug delivery of therapeutic agents and uses thereof

A therapeutic composition having wet adherent properties and particularly useful for delivery of medicaments to mucosal surfaces comprises a therapeutically effective amount of a medicament dispersed in a base material comprising from about 3 to 15% by weight of a water soluble salt of a copolymer of methyl vinyl ether and maleic acid or anhydride and from about 85 to 97% by weight of polyethylene glycol. Formulations of the base material with triamcinolone acetonide and lidocaine are particularly efficacious in the treatment of recurrent aphthous ulcers.

Bioadhesive polyethylene glycol ointment for medicaments

A therapeutic ointment having wet adherent properties and particularly well suited for delivery of medicaments to mucosal surfaces includes a base material comprising from about 3 to 15% by weight of a water soluble salt of a copolymer of methyl vinyl ether and maleic acid or anhydride in a polyethylene glycol ointment. Formulations of the base material with triamcinolone acetonide and lidocaine are particularly efficacious in the treatment of recurrent aphthous ulcers.

Thomas G. Gerding

Papers

Influence of plasticizers and drugs on the physical-mechanical properties of hydroxypropylcellulose films prepared by hot melt extrusion.

Stick formulations for topical drug delivery of therapeutic agents and uses thereof

Bioadhesive polyethylene glycol ointment for medicaments

Polyethylene glycol ointment for apthous ulcers