They should have a suitable glass transition temperature tg in the range of 50180 c, low hygroscopicity, stability at extrusion temperature and no. A major challenge is the transfer from a lab to a production level, since the combination of several unit operations within one apparatus leads to complex conditions for such a continuous manufacturing process. Hot melt extrusion is the new mixer extrusion range that builds on the proven umang technology and its benefits. 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. Hot melt extrusion resulted in an even higher mixing capability. Hot melt extrudates hmes of indomethacin ind with eudragit epo and kollidon va 64 and those of itraconazole itz with hpmcaslf and kollidon va 64 were manufactured using a leistritz twin screw extruder. 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. A twinscrew 16 extruder coupled with a leistritz micro pelletizer lmp cutting machine was utilized 17 for the extrusion of different types normal, waxy, and highamlyose of corn. About 34% of these are plastic extruders, 1% are rubber extruders, and 7% are coating machines.
Hotmelt extrusion technology and pharmaceutical application. This was accomplished by converting the poorly watersoluble crystalline form of carbamazepine to the more watersoluble amorphous form utilizing polymeric blends. Rheological behavior of the polymer depends largely upon temperature, process history and pressure. Pdf twin screw extrusion for pharmaceutical processes. Pdf solubility and dissolution rate enhancement of.
While there are several platform technologies and manufacturing techniques to produce amorphous solid dispersions, hot melt extrusion hme is a leading approach based on mature process understanding, small process footprint, continuous operation and readily scalable. Foam hot melt extrusion of an eudragit nifedipine matrix formulation using supercritical co2 t. Hotmelt extrusion is one of the most widely applied processing technologies in the plastic, rubber and food industry. Jun 26, 2012 hot melt extrusion hme melting a substance and forcing it through an orifice under controlled conditions to form a new material is an emerging processing technology in the pharmaceutical industry for the preparation of various dosage forms and drug delivery systems, for example granules and sustained release tablets. Pdf hotmelt extrusion hme is a promising technology for the production of new chemical entities in the developmental pipeline and for. 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.
Mechanochemical synthesis of pharmaceutical cocrystal. Hotmelt extrusion technique was first invented for the. Hotmelt extrusion of sugarstarchpellets pdf free download. Solubility and dissolution rate enhancement of lumefantrine using hot melt extrusion technology with physicochemical characterisation. Foam hot melt extrusion of an eudragit nifedipine matrix. The two main advantages of this process over other manufacturing processes are its ability to create very complex crosssections, and to work materials that are brittle, because the material only encounters compressive and shear stresses. University of groningen innovative platform technologies for. Bioavailability enhancement of atovaquone using hot melt. Differential scanning calorimetry and polarized light. Downstream processing from hotmelt extrusion towards tablets. Soluplus is a watersoluble copolymer with the average molecular weight ranging from 90,000 to 140,000 gmol, and it is capable of solubilizing poorly watersoluble drugs. By drawing on continuous processing, hot melt extrusion is more economical and can be used for abuse deference and taste masking applications. By addressing basic operation principles and critical aspects of hme as well as cutting edge trends of extrusion based manufacturing technologies the reader is able to understand the effective processes needed to develop pharmaceutical products from lab scale to commercialization.
This inclusive text describes hot melt extrusion for pharmaceutical applications, focusing on the materials used for. Hot melt extrusion technology, approach of solubility enhancement. Processtechnologyofhotmelt extrusionhme hotmelt extrusion technique was. Interest in hotmelt extrusion techniques for pharmaceutical applications is growing rapidly with. The focus was to identify materialsparing approaches to develop bioavailable and stable asd including scale.
By the specific characteristics such as a precise shear rate application and a. Hot melt extrusion an emerging drug delivery technology 01 aug 2011 1 d. Today this technology has found its place in the array of pharmaceutical. Hme has proven to be a robust method of producing numerous drug delivery systems like modified, controlled and targeted drug delivery systems. Hot melt extrusion an emerging drug delivery technology. Each formulation produced by hot melt extrusion has a process energy. Comparison between hotmelt extrusion and spraydrying for. Repkas most important scientific accomplishments involve the advancement of melt extrusion technology. Hot melt extrusion technique and its pharmaceutical. Some of the most wellknown applications are for tastemasking of drugs 35, solubilityenhancement. Department of pharmaceutical sciences, medway school of science, university of. Pharmaceutical applications advances in pharmaceutical technology hot melt extrusion hme melting a substance and forcing it through an orifice under controlled conditions to form a new material is an emerging processing technology in the pharmaceutical industry for the preparation of various dosage forms and drug delivery systems, for example granules and sustained. Fda process analytical technology pat scheme for designing, analyzing, and controlling the manufacturing process via quality control measurements during active extrusion process. Jan 02, 2018 hot melt extrusion is an emerging technology for the continuous manufacture of drugs within the pharmaceutical industry.
Wang 2,3 1foster corporation, 45 ridge road putnam, ct 06260. 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. Hot melt extrusion hme is a proven technology for bioavailability enhancement of poorly soluble apis. Advantages of hot melt extrusion for the controlled. The process has been utilized readily in the plastics industry for over a century and has been used to manufacture medical devices for several decades.
Process analytical technology pat can be viewed from many perspectives. Hot melt extrusion technology, approach of solubility. This paper introduces hot melt extrusion 15 hme as an alternative method to manufacture sugarstarchpellets. Introduction melt extrusion technology is becoming a more widely accepted technology for development and production for pharmaceutical dosages forms for many different reasons. Hot melt extrusion technology has gained considerable popularity in the pharmaceutical industry due to the advantages it offers over traditional manufacturing techniques and provides an efficient production process that enhances the quality of products. Functional excipients, such as surfactants, are often added to further aid in. Process technology of hot melt extrusion hme hot melt extrusion technique was first invented for the manufacturing of lead pipes at the end of the eighteenth century. This technical brief focuses from a highlevel perspective. In recent years hot melt extrusion hme has been used extensively in solubility enhancement applications for polymerbased amorphous solid dispersions provided the drug substance is thermally stable. In this paper we propose, for the first time, the use of hot melt extrusion for the mechanochemical synthesis of pharmaceutical cocrystals in the presence of a meltable binder.
Thermo gravimetric analysis studies showed that the drug was thermally stable under the employed extrusion parameters. Various approaches have been adopted to address this including preparation of solid dispersions and solid solutions. Jan 14, 2015 optimelt is catalents unique ability to formulate, develop and commercialize hot melt extrusion processes and integrate these into differentiated final dosage forms. Sincethen,ithasbeenusedintheplastic,rubber, and food manufacturing industry to produce items ranging from pipes to sheets and bags. Since then, it has been used in the plastic, rubber, and food manufacturing industry to produce items ranging from pipes to sheets and bags. It was the researchers goal to prepare a dosage form in a simple and continuous manner. Thermal degradation was recognized as a limitation of this hot melt process. Hot melt extruder pharmaceutical machine manufacturers and. American leistritz extruder corporation, somerville, nj, usa.
Here the use of the spraydried copolymer did not show any benefit concerning the kinetic miscibility of the drug and copolymer, but it resulted in a remarkable decrease in the torque experienced by the extruder allowing extrusion at lower temperature and torque. What are the advantages of using a hot melt extrusion process for drug formulation development. The technology itself can be described as a process in which a material melts or softens under elevated temperature and pressure and is forced through an orifice by screws. Purpose the aim of this paper is the development of a process control concept for a hot melt extrusion hme and pelletization process. Solid dispersions may be prepared by fusion, solvent evaporation, supercritical fluid technology, and hot melt extrusion hme. Downstream processing from hotmelt extrusion towards. Melt energy is derived from the input temperatures, the shear forces and the mechanical energy from the shafts. Process energy is comprised of mechanical and thermal energies that ensure homogenous mixing without degradation of the api or excipients.
In this approach, we examine excipients that are amenable to hot melt extrusion, forming a suspension of cocrystal particulates embedded in a pharmaceutical matrix. Hot melt extrusion hme is a promising technology for the production of new chemical. Process technology to pharmaceutical products article pdf available december 2012 with 4,893 reads how we measure reads. Hot melt extrusion in the pharmaceutical and food industries. Melt extrusion materials, technology and drug product. Gold chemical and materials engineering, university of dayton, dayton, ohio, usa. A greater degree of conveying and much shorter residence times are achievable with an intermeshing setup. The choice of an appropriate polymer is crucial for extrusion process.
With the use of hme we can increase solubility and bioavailability of the api. Appropriate thermoplastic behavior is a prerequisite of any polymer to be used in hot melt extrusion. Hot melt extrusion on twinscrewextruders has been established as a standard processing technique for pharmaceutical products. Hot melt extrusion continuous extrusion process for pharmaceutical masses. Hot melt extrusion is extrusion compounding two or more ingredients which have been combined in defined proportions, distinguishable from their original state in that the characteristics of the whole is unique from that of the original constituents. Today, hme is an accepted process for creating solid dispersions of apis. Polymers for hotmelt extrusion hme should have the thermoplastic behavior to enable melt extrusion to take place. May 19, 2017 hot melt extrusion hme is the process of applying heat and pressure to melt a polymer and force it though an orifice in a continuous process.
Hot melt extrusion technology kurt kortokrax sales account manager thermo fisher scientific. Over the last three decades industrial adaptability has allowed hotmelt extrusion hme to gain wide acceptance and has already established its place in the. Maniruzzaman m1, boateng js, snowden mj, douroumis d. A wide variety of hot melt extruder machine options are available to you, such as screw design, application, and plastic processed. Rheological data obtained during an extrusion process can provide information on the macromolecular structure of the melt and its morphology. Hot melt extrusion for amorphous solid dispersions.
Repka 0 1 0 pii center for pharmaceutical technology, school of pharmacy, the university of mississippi, oxford, mississippi 38677, usa 1 department of pharmaceutics and drug delivery, school of pharmacy, the university of. Many of these systems are directed toward the solubilization and delivery of poorly soluble bioactives via hot melt extrusion technology, which is a primary focus of his research. The use of hot melt extrusion hme within the pharmaceutical industry is steadily increasing, due to its proven ability to efficiently manufacture novel products. Hot melt extrusion technology for continuous manufacturing. Unlike other formulation options, hot melt extrusion technology is solventfree. What is melt extrusion and how does it help us make new. Hot melt extrusion is one of the most widely applied processing technologies in the plastic, rubber and food industry. The extruder, by its nature, is a continuous instrument, so, it lends itself to continuous production. Optimelt is catalents unique ability to formulate, develop and commercialize hot melt extrusion processes and integrate these into differentiated final dosage forms. The samples were collected after specified time periods for 3 months. Hot melt extrusion hme is a promising technology for the production of new chemical entities in the developmental pipeline and.
Hot melt extrusion,particle sciences drug development services,2011,vol3,p. Hotmelt extrusion technology technical brief capsugel. Inline monitoring of a hot melt extrusion process by near. Hotmelt extrusion of modified release pellets influence of the formulation and extrusion process on extended and enteric release profile malin linden department of chemical and biological engineering chalmers university of technology abstract the interest in hotmelt extrusion in the pharmaceutical industry has increased rapidly during the. Mar 20, 2012 hot melt extrusion technology kurt kortokrax sales account manager thermo fisher scientific 2. Encyclopedia of pharmaceutical technology 19, 203226, 2007.
Oct 20, 2015 the objective of the study was to develop an amorphous solid dispersion asd for an insoluble compound x by hot melt extrusion hme process. 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 technique has gained popularity in the pharmaceutical industry in the recent years as exemplified by the plethora of hme patents filed globally repka et al. Polymeric formulations for drug release prepared by hot melt extrusion the quality of the final products. Jan 08, 2015 in this study, the objective was to improve the solubility and physical stability of carbamazepine cbz using hot melt extrusion technology. Pdf over the last three decades industrial adaptability has allowed hotmelt extrusion hme to gain wide acceptance and has already established its. Hot melt extrusion an emerging drug delivery technology monika vasant pawar m. An increasingly explored technology in the pharmaceutical industry, hme has proven to be a robust and viable method for pharmaceutical applications capable of creating a diverse range of dosage forms with clinical benefits. Used in several industries, hme is a combination of melting and mechanical energy to improve continuous processing for. 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. Hot melt extrusion hme is well known process for the plastic industries but it is well accepted by the pharmaceutical industries for the last three decays. Global pharmaceutical hot melt extrusion equipment market.
Hot melt extrusion of orally disintegrating films author margarethe richter thermo fisher scientific, karlsruhe, germany key words orally disintegrating films, odf, pharmaceutical technology, hot melt extrusion, hme executive summary orally disintegrating films odfs are an appealing dosage form because they allow safe, easy and exact dose. Furthermore, the use of reverseconveying and forwardconveying elements, kneading blocks and other intricate designs as. Hot melt extrusion hme is the processing of polymeric materials above their glass transition temperature tg in order to effect molecular level mixing of thermoplastic binders andor polymers and active compounds. In this respect, the technology competes directly with spray drying and may offer advantages in terms of cost and throughput. Proven technology hot melt extrusion is a technique for manufacturing amorphous solid dispersions in which the drug substance is melted or dissolved within a dispersion carrier and mixed to produce and stabilize the amorphous form of the drug substance. Hot melt extrusion is an efficient technology for producing solid molecular dispersions with considerable advantages over solventbased. Hot melt extrusion hme melting a substance and forcing it through an orifice under controlled conditions to form a new material is an emerging processing technology in the pharmaceutical industry for the preparation of various dosage forms and drug delivery systems, for example granules and sustained release tablets. Extrusion is a process used to create objects of a fixed crosssectional profile. From process to pharmaceutical applications 7 equivalent from a processing perspective. One key advantage is the ability to produce a variety of formulations, such as solid dose forms, which improve drug bioavailability. Stabilityenhanced hotmelt extruded amorphous solid. Hot melt extrusion hme is a widely applied technology in the plastics industry. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system ii bcs class ii, which are characterized.
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