Furthermore, process analytical technology pat tools and the integration of such tools in process control environment are presented. Screw elements, screw rotation and screw speeds can be custom tailored for each formulation. Hot melt extrusion was carried out using thermo fisher scientifics eurolab 16 a 16mm corotating twinscrew extruder figure 1. May 16, 2014 hot melt extrusion hme is a suitable process to produce a wide range of pharmaceutical dosage forms, like tablets, capsules, lozenges or implants. The objective of this study was to prepare aripiprazole ariloaded solid dispersions sds to enhance solubility and dissolution via hotmelt extrusion hme technology. Jan 21, 2020 hot melt extrusion hme is a common manufacturing operation in the food and polymer industries and is becoming increasingly deployed in the pharmaceutical industry. Hot melt extrusion hme is a common manufacturing operation in the food and polymer industries and is becoming increasingly deployed in the pharmaceutical industry. Pharmaceutical manufacturers use conical and twinscrew extruders to mix drug molecules with bioactive polymers where drug ingredients are poorly soluble or. Hot melt extrusion is a proven, commercially validated process for formulating poorly watersoluble apis and creating controlled release. Hme involves the mixing of a drug with one or more. Hot melt extrusion continuous extrusion process for pharmaceutical masses. Downstream processing from hotmelt extrusion towards tablets. Development of an ointment formulation using hot melt extrusion technology ajinkya m. To develop suitable formulations, it is desirable to keep the extrusion formulation.
Hot melt extrusion is the new mixer extrusion range that builds on the proven umang technology and its benefits. Hot melt extrusion hme is a suitable process to produce a wide range of pharmaceutical dosage forms, like tablets, capsules, lozenges or implants. Bhagurkar, 1 muralikrishnan angamuthu, 1 hemlata patil, 1 roshan v. Of particular interest is the use of hme to disperse active pharmaceutical ingredients apis in a matrix at the molecular level, thus forming solid solutions. By drawing on continuous processing, hot melt extrusion is more economical and can be used for abuse deference and taste masking applications. Solid dispersions can be obtained from various techniques such as hot melt extrusion hme, spray drying, and coprecipitation 35. Tiwari, 1 abhijeet maurya, 1 seyed meysam hashemnejad, 2 santanu kundu, 2 s. Hotmelt extrusion hme is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In the hot melt extrusion process, the formulation is processed above the glass transition temperature of the polymerapi adjuvant system to mix the active ingredient with the. Development of an ointment formulation using hotmelt extrusion technology ajinkya m. Hotmelt extrusion hme is a wellaccepted and extensively studied method for preparing numerous types of drug delivery systems and dosage forms. Hotmelt extrusion is an efficient processing method for obtaining solid dispersions. Hot melt extrusion technology for continuous manufacturing.
Introduction to date hme has emerged as a novel processing technology. Preparation and evaluation of aripiprazoleloaded ph. Unlike other formulation options, hot melt extrusion technology is solventfree. In drug discovery and development, industry estimates that more than 50% of active. Polymers for hot melt extrusion must exhibit thermoplastic characteristics and must be thermally stable at the proper extrusion temperature. In the 1980s, basf became the first company to apply it to the production of pharmaceuticals for enhancing the solubility and bioavailability of poorly soluble actives. Hot melt extrusion hme is a method that has been used quite extensively.
Jul 10, 2015 hot melt extrusion hme is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. One key advantage is the ability to produce a variety of formulations, such as solid dose forms, which improve drug bioavailability. Pharmaceutical applications is an essential multidisciplinary guide to the emerging pharmaceutical uses of this processing technology for researchers in academia and industry working in drug formulation and delivery, pharmaceutical engineering and. Hot melt extruded granules were observed to be less spherical than highshear melt granules and had lower bulk and tap densities. In general, realtime pharmaceutical process verification is.
This chapter focuses on continuous hot melt extrusion hme processing as well as on the continuous downstream options that are available. Solid dispersions of compound x were prepared using polyvinyl pyrrolidone covinyl acetate 64 pvp va64, soluplus, and hypromellose acetate. Sincethen,ithasbeenusedintheplastic,rubber, and food manufacturing industry to produce items ranging from pipes to sheets and bags. Hot melt extrusion hme is a promising technology for the production of new chemical.
In developing an hme drug system, the glass transition and melting temperatures are critical factors. Active pharmaceutical ingredient, hot melt extrusion, raman imaging introduction an important area for the advancement of pharmaceuticals is in product formulation development. Controlled release tablets containing a poorly watersoluble drug, indomethacin idm, acrylic polymers eudragit rd 100, eudragit l 100, or eudragit s 100, and triethyl citrate tec were. Twin screw extruders are frequently used to prepare solid dispersions due to their distributive and dispersive capacities, and short transit time. Jan 12, 2016 the objective of the study was to identify the extragranular component requirements level and type of excipients to develop an immediate release tablet of solid dispersions prepared by hot melt extrusion hme process using commonly used hme polymers. Hotmelt extrusion hme pharmaceutical applications capsugel. Hme is recently being used in healthcare industry to manufacture medical devices, amorphous solid dispersion asd to enhance bioavailability of poorly soluble api, targeted release drug delivery systems, implants, bioadhesive. Polymers for hotmelt extrusion must exhibit thermoplastic characteristics and must be thermally stable at the proper extrusion temperature.
This technology can be used to produce the filaments that are required to be used in fused deposition modelling fdm 3d printers. Solid dispersions represent a promising formulation approach for overcoming todays major challenge in pharmaceutical industry of developing bioavailable solid dosage form for more than 50% of drug candidates that are poorly water soluble 1,2. Through dsc and a matlab software script developed by the authors. Tiwari,1 abhijeet maurya,1 seyed meysam hashemnejad,2 santanu kundu,2 s. Scope of the study the report includes revenue generated from sales of hot melt extruders in all regions and important countries in these regions. Like freeze drying or spray drying the melt extrusion process is used to achieve solid dispersions, what means.
Over the last three decades industrial adaptability has allowed hotmelt extrusion hme to gain wide acceptance and has already established its place in the broad spectrum of manufacturing operations and pharmaceutical research developments. Nordson offers multiple hot melt glue machines designed to make packaging, binding, assembly, and other tasks quick and effortless. The main driver of increased use of hme technology in the pharmaceutical. The hotmelt extrusion hme technology was established in the early 1930s and was originally used for the manufacturing of plastics and rubber products. The active pharmaceutical ingredient api delivery method can be as important as the drug itself.
Furthermore, the hot melt extrusion process and hot melt extrusion equipment are readily scalable, from lab to pilot plantscale, through to commercial production. Solubility screenings of various polymers and acidifiers were performed to select appropriate excipients for the sd. Research article development of an ointment formulation using. The commercial onedimensional 1d simulation software ludovic. Our extruders can be configured for a variety of processing approaches including coextrusion. The main drivers of increased hot melt extrusion use in the pharmaceutical and otc. Downstream processing from hotmelt extrusion towards. Hot melt extrusion has been widely used as a processing method for many purposes, including formation of a solid molecular dispersion to increase the bioavailability of poorly soluble drugs.
Over a decade of experience in amorphous dispersion and hme formulation. Hot melt extruder pharmaceutical machine manufacturers and. Global pharmaceutical hot melt extrusion equipment market. Hotmelt extruded filaments based on pharmaceutical grade.
Hot melt extrusion hme is a method that has been used quite extensively in the plastics industry to produce a wide assortment of plastic products in a variety of forms. Polymers present in the formulation of the drug product are probably used for the. Today, hme is an accepted process for creating solid dispersions of apis. Pharmaceutical hot melt extrusion market global industry. Ari was chosen due to its poorly watersoluble properties. Pdf pharmaceutical applications of hotmelt extrusion. Hme can be used for immediate release as well as for sustained release formulations. A solid dispersion is defined as a formulation of poorly soluble compounds as solid dispersions might lead to particle size reduction, improved wetting, reduced agglomeration, changes in the physical state of the drug and possibly dispersion on a. Validation of modelbased melt viscosity in hotmelt extrusion. Investigating process parameter mechanism for successful. Hot melt extrusion system for pharmaceutical applications. Effective delivery of many of bcs class ii compounds with low solubility can be enabled with amorphous dispersions made by hot melt extrusion hme.
Evaluating active ingredients in pharmaceutical hot melt. Hot melt extrusion 1045 passed through a 14mesh screen to form granules. Hot melt extrusion optimelt hot melt extrusion technology to improve. Additionally, hme provides greater drug bioavailability. Due to the continuous, efficient nature of hme, which combines several polymer drug mixing and processing steps, it is often used to manufacture large, expensive batches of. Repka department of pharmaceutics and drug delivery, school of pharmacy, the university of mississippi, university, mississippi 38677 usa. To improve its antimalarial activity, solid dispersion formulation using hot melt extrusion technology was prepared. Content uniformity analysis of the hot melt extruded granules exhibited less variability and decreased range relative to the. The pharmamv software platform, from perceptive engineering, was connected to the hme unit to perform automated dynamic doe tests. Browse industrial hot melt glue guns and equipment offered by nordson simplify the process of dispensing hot melt adhesives with industrial hot melt glue guns that improve productivity and minimize waste. Controlled release tablets containing a poorly watersoluble drug, indomethacin idm, acrylic polymers eudragit rd 100, eudragit l 100, or eudragit s 100, and triethyl citrate tec were prepared by hot melt extrusion.
Hotmelt extrusion hme has been revealed as a successful technology for a large. Hot melt extrusion is the upgraded version of twin screw extruder with heating as an element, the whole process involves hopper for feeding the raw material along with waxes which is pre mixed in solid form. Advanced pharmaceutical applications of hotmelt extrusion. Hot melt extrusion hme is a wellknown process in plastic industry to produce products of uniform shape and density and its application dates back to the 1930s. Hot melt extrusion is an emerging technology for the continuous manufacture of drugs within the pharmaceutical industry. Hot melt extrusion is a sophisticated technology used to develop solid dispersion dosage forms for improved drug solubility and bioavailability, a common challenge for formulation scientists in the development of drug products today. Bhagurkar,1 muralikrishnan angamuthu,1 hemlata patil,1 roshan v.
Lumefantrine lumf is an antimalarial drug that exhibits poor oral bioavailability, in consequence of its poor aqueous solubility. A full factorial experimental design with 19 experiments was used to evaluate the effect of several process variables barrel temperature. Hot melt extrusion hme is becoming an important technology within the pharmaceutical industry as a means for formulating poorly watersoluble active pharmaceutical ingredients apis. Pharmaceutical applications is an essential multidisciplinary guide to the emerging pharmaceutical uses of this processing technology for researchers in academia and industry working in drug formulation and delivery, pharmaceutical engineering and processing, and polymers and materials science. Nowadays, one of the major challenges in pharmaceutical small molecule formulation. The extrudability of a polymer is mainly determined by t g or t m and melt viscosity. Hme has already been demonstrated as a robust, novel technique to make solid dispersions in order to provide time controlled, modified, extended, and.
Development of tablet formulation of amorphous solid. Hot melt extrusion hme technology is prominent in the pharmaceutical industry. Oct 06, 2009 hot melt extrusion hme is becoming an important technology within the pharmaceutical industry as a means for formulating poorly watersoluble active pharmaceutical ingredients apis. An important area for the advancement of pharmaceuticals is in product formulation development. Like freeze drying or spray drying the melt extrusion process is used to achieve solid dispersions, what means that the drug is embedded in. Hot melt extrusion hme is a proven technology for bioavailability enhancement of poorly soluble apis. In dsc, a linear or isothermal temperature program is applied as a function of time or. Research article development of an ointment formulation. Hme manufacture of amorphous dispersion involves the melting of a drug substance with an appropriate polymeric excipient in a corotating twinscrew extruder. Oct 20, 2015 hot melt extrusion hme is a wellknown process in plastic industry to produce products of uniform shape and density and its application dates back to the 1930s. Hotmelt extrusion is a sophisticated technology used to develop solid dispersion dosage forms for improved drug solubility and bioavailability, a common challenge for formulation scientists in the development of drug products today.
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