direct compounding extrusion of APIs into devices whose primary function is controlled release of a drug. Examples include drug-eluting patches, implantable rods, and profiles of various shapes, such as coextruded vaginal rings imbedded with anti-HIV or contraceptive drugs for controlled release from the drug-loaded core through the exterior layer(1)
.
Hot-melt extrusion APIs are also being melt compounded into inactive polymeric carriers (i.e. excipients) to manufacture drugs in solid dosage form, such as tablets. While the plastics industry calls this mixing process compounding extrusion, the pharmaceutical industry calls it “hot- melt extrusion” (HME). Use of twin-screw melt extrusion in pharmaceutical applications emerged in the past decade, and is increasingly being used to manufacture drugs. Examples of common polymeric excipients include polyvinylpyrrolidone (povidone) and cellulose derivatives like hydroxypropyl methylcellulose (HPMC or hypromellose). A key driver for the use of melt extrusion is to
Particle Sciences is using this Leistritz ZSE 18 mm extruder to develop
thermoplas- tics-based drug-eluting products
improve the oral bioavailability (i.e. how much of the drug eventually reaches the bloodstream) of APIs. Some APIs are poorly water soluble, which means that the rate at which they dissolve limits their absorption and oral bioavailability. Melt extrusion has the capacity to enhance dissolution rates and oral bioavailability of some poorly soluble drug substances, which makes it a valuable tool(1)
. Since an increasing number of new drug
candidates are poorly soluble, the need for melt extruders is growing. This trend is further driven by the desire in the
pharmaceutical industry to improve efficiency by moving away from batch processing to continuous processing in some applications. The US Food and Drug Administration (FDA) is promoting the idea of quality-by-design (QbD) for pharmaceutical processing, including a process
analytical technology (PAT) initiative, in which critical process parameters are measured and controlled, preferably in-line, in order to ensure final product quality. The FDA views continuous processing as a way to improve quality and safety by managing variability(2)
.
Continuous processes, which are more predictable and consistent than batch processes, are more repeatable and lend themselves more easily to controlling process parameters in order to control variability. Melt extrusion is one type of continuous process that the pharmaceuti- cal industry is adapting.
Regulatory requirements A distinguishing characteristic of medical compounding is the need to comply with regulatory requirements, which are specific to the country in which the product will be sold. Production of drugs and devices for the US must follow current good manufacturing processes (cGMP), which are quality system guidelines from the FDA. “These guidelines cover a broad range of areas from
the Code of Federal Regulations (21CFR 211: organiza- tion and personnel; buildings and facilities; equipment; control of components and drug product containers and closures; production and process controls etc). The FDA wants manufacturers to guarantee quality, safety, identity, and efficacy (i.e. the potency) of each batch,” explains Dr. Andrew Loxley, director of new technologies at Particle Sciences. This contract research organization provides drug development services, including develop- ment of formulations using hot-melt extrusion. Under cGMP guidelines, the materials of contact
(MOC) with the drug product, which would include parts of the extruder and auxiliaries, must be evaluated. In general, all MOCs should be cleanable, non-corrosive, and non-additive (i.e. not add to or change the products that touch them). Because some APIs can interact with even hardened
stainless steels, the appropriate MOC depends on the formulations being run in the equipment. Equipment