The interest in hotmelt extrusion as a drug delivery technology for the production of solid dispersion is growing rapidly. Advanced pharmaceutical applications of hotmelt extrusion. Furthermore, the hot melt extrusion process and hot melt extrusion equipment are readily scalable, from lab to pilot plantscale, through to commercial production. 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. 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. Sincethen,ithasbeenusedintheplastic,rubber, and food manufacturing industry to produce items ranging from pipes to sheets and bags. 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. Validation of modelbased melt viscosity in hotmelt extrusion. 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. Content uniformity analysis of the hot melt extruded granules exhibited less variability and decreased range relative to the. In drug discovery and development, industry estimates that more than 50% of active. Hotmelt extruded filaments based on pharmaceutical grade. 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. 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.
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. Hot melt extrusion is a proven, commercially validated process for formulating poorly watersoluble apis and creating controlled release. Over a decade of experience in amorphous dispersion and hme formulation. The extrudability of a polymer is mainly determined by t g or t m and melt viscosity. 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.
Polymers for hotmelt extrusion must exhibit thermoplastic characteristics and must be thermally stable at the proper extrusion temperature. Hot melt extrusion continuous extrusion process for pharmaceutical masses. A full factorial experimental design with 19 experiments was used to evaluate the effect of several process variables barrel temperature. Repka department of pharmaceutics and drug delivery, school of pharmacy, the university of mississippi, university, mississippi 38677 usa. Through dsc and a matlab software script developed by the authors. Unlike other formulation options, hot melt extrusion technology is solventfree. 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.
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. Investigating process parameter mechanism for successful. Hot melt extrusion hme technology is prominent in the pharmaceutical industry. Hotmelt extrusion hme pharmaceutical applications capsugel. Research article development of an ointment formulation using. Hot melt extrusion is an efficient processing method for obtaining solid dispersions. In general, realtime pharmaceutical process verification is. Despite the difference in polarity of the plasticizers. The main driver of increased use of hme technology in the pharmaceutical. Research article development of an ointment formulation. Hot melt extruded granules were observed to be less spherical than highshear melt granules and had lower bulk and tap densities. The hotmelt extrusion hme technology was established in the early 1930s and was originally used for the manufacturing of plastics and rubber products. 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.
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. 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. Lumefantrine lumf is an antimalarial drug that exhibits poor oral bioavailability, in consequence of its poor aqueous solubility. Downstream processing from hotmelt extrusion towards. Global pharmaceutical hot melt extrusion equipment market. Nowadays, one of the major challenges in pharmaceutical small molecule formulation. Polymers present in the formulation of the drug product are probably used for the.
Pharmaceutical manufacturers use conical and twinscrew extruders to mix drug molecules with bioactive polymers where drug ingredients are poorly soluble or. 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. Scope of the study the report includes revenue generated from sales of hot melt extruders in all regions and important countries in these regions. Additionally, hme provides greater drug bioavailability. Hot melt extrusion system for pharmaceutical applications. Like freeze drying or spray drying the melt extrusion process is used to achieve solid dispersions, what means that the drug is embedded in. To develop suitable formulations, it is desirable to keep the extrusion formulation.
Introduction to date hme has emerged as a novel processing technology. Hot melt extrusion hme is becoming an important technology within the pharmaceutical industry as a means for formulating poorly watersoluble active pharmaceutical ingredients apis. Our extruders can be configured for a variety of processing approaches including coextrusion. Pharmaceutical hot melt extrusion market global industry. Hot melt extrusion hme is a promising technology for the production of new chemical. 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. 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. Nordson offers multiple hot melt glue machines designed to make packaging, binding, assembly, and other tasks quick and effortless. Today, hme is an accepted process for creating solid dispersions of apis.
Furthermore, process analytical technology pat tools and the integration of such tools in process control environment are presented. In developing an hme drug system, the glass transition and melting temperatures are critical factors. Development of tablet formulation of amorphous solid. The commercial onedimensional 1d simulation software ludovic. Twin screw extruders are frequently used to prepare solid dispersions due to their distributive and dispersive capacities, and short transit time. Hot melt extrusion hme is a method that has been used quite extensively. Hme manufacture of amorphous dispersion involves the melting of a drug substance with an appropriate polymeric excipient in a corotating twinscrew extruder. Hot melt extrusion 1045 passed through a 14mesh screen to form granules. In dsc, a linear or isothermal temperature program is applied as a function of time or. Solid dispersions of compound x were prepared using polyvinyl pyrrolidone covinyl acetate 64 pvp va64, soluplus, and hypromellose acetate. In drug discovery and development, industry estimates that more than 50% of. Like freeze drying or spray drying the melt extrusion process is used to achieve solid dispersions, what means. Effective delivery of many of bcs class ii compounds with low solubility can be enabled with amorphous dispersions made by hot melt extrusion hme. To improve its antimalarial activity, solid dispersion formulation using hot melt extrusion technology was prepared.
Polymers for hot melt extrusion must exhibit thermoplastic characteristics and must be thermally stable at the proper extrusion temperature. The pharmamv software platform, from perceptive engineering, was connected to the hme unit to perform automated dynamic doe tests. Effective delivery of many of bcs class ii compounds with low solubility can be enabled with amorphous dispersions made by hotmelt extrusion hme. An important area for the advancement of pharmaceuticals is in product formulation development. Hotmelt extrusion hme is a wellaccepted and extensively studied method for preparing numerous types of drug delivery systems and dosage forms.
Solubility screenings of various polymers and acidifiers were performed to select appropriate excipients for the sd. The objective of this study was to prepare aripiprazole ariloaded solid dispersions sds to enhance solubility and dissolution via hotmelt extrusion hme technology. 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. Hot melt extrusion technology for continuous manufacturing. 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. Hot melt extrusion hme is a common manufacturing operation in the food and polymer industries and is becoming increasingly deployed in the pharmaceutical industry. Evaluating active ingredients in pharmaceutical hot melt. 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. This chapter focuses on continuous hot melt extrusion hme processing as well as on the continuous downstream options that are available. Preparation and evaluation of aripiprazoleloaded ph.
Hotmelt extrusion is an efficient processing method for obtaining solid dispersions. One key advantage is the ability to produce a variety of formulations, such as solid dose forms, which improve drug bioavailability. 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. Hme involves the mixing of a drug with one or more. Hotmelt extrusion hme has been revealed as a successful technology for a large. Hot melt extrusion is an emerging technology for the continuous manufacture of drugs within the pharmaceutical industry. Some major challenges that still have to be faced in the field of drug delivery e.
Processtechnologyofhotmelt extrusionhme hotmelt extrusion technique was. Hot melt extrusion hme is a suitable process to produce a wide range of pharmaceutical dosage forms, like tablets, capsules, lozenges or implants. Development of an ointment formulation using hot melt extrusion technology ajinkya m. Development of an ointment formulation using hotmelt extrusion technology ajinkya m. This technology can be used to produce the filaments that are required to be used in fused deposition modelling fdm 3d printers. 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 extrusion was carried out using thermo fisher scientifics eurolab 16 a 16mm corotating twinscrew extruder figure 1. Active pharmaceutical ingredient, hot melt extrusion, raman imaging introduction an important area for the advancement of pharmaceuticals is in product formulation development. By drawing on continuous processing, hot melt extrusion is more economical and can be used for abuse deference and taste masking applications. Hot melt extrusion optimelt hot melt extrusion technology to improve. Solid dispersions can be obtained from various techniques such as hot melt extrusion hme, spray drying, and coprecipitation 35. Hot melt extrusion is the new mixer extrusion range that builds on the proven umang technology and its benefits.
The active pharmaceutical ingredient api delivery method can be as important as the drug itself. 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. The main drivers of increased hot melt extrusion use in the pharmaceutical and otc. 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. 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. Ari was chosen due to its poorly watersoluble properties. Bhagurkar, 1 muralikrishnan angamuthu, 1 hemlata patil, 1 roshan v. Hot melt extrusion hme is a wellaccepted and extensively studied method for preparing numerous types of drug delivery systems and dosage forms. Hme has already been demonstrated as a robust, novel technique to make solid dispersions in order to provide time controlled, modified, extended, and. Dec 01, 2014 an important area for the advancement of pharmaceuticals is in product formulation development.
Solid dispersions by hotmelt extrusion pharmaceutical. Screw elements, screw rotation and screw speeds can be custom tailored for each formulation. Hot melt extrusion hme is a proven technology for bioavailability enhancement of poorly soluble apis. Tiwari, 1 abhijeet maurya, 1 seyed meysam hashemnejad, 2 santanu kundu, 2 s. Hot melt extruder pharmaceutical machine manufacturers and. Downstream processing from hotmelt extrusion towards tablets. 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. Processing of amorphous solid dispersions for poorly soluble drugs duration. Tiwari,1 abhijeet maurya,1 seyed meysam hashemnejad,2 santanu kundu,2 s. Hme can be used for immediate release as well as for sustained release formulations. Hotmelt extrusion hme technology is prominent in the pharmaceutical industry. Bhagurkar,1 muralikrishnan angamuthu,1 hemlata patil,1 roshan v. 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. Pdf pharmaceutical applications of hotmelt extrusion.