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 medical books hot melt. 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. Repkas most important scientific accomplishments involve the advancement of melt extrusion technology. Hme has already been demonstrated as a robust, novel technique to make solid dispersions in order to provide time controlled, modified, extended, and. Us3410938a method and apparatus for hot melt extrusion. Single screw extruders are primarily used for melting and conveying polymers to extrude them into continuous shapes, whereas twin screw extruders are used for melt mixing polymers with additional materials pigments, fillers, reinforcers, and apis, and for devolatilization. With the use of hme we can increase solubility and bioavailability of the api. Hot melt extrusion hot melt extrusion hme is used for blending, melting, extrusion and shaping in a single step process.
In this work, terahertz thz raman spectroscopy was introduced as a novel empirical approach to determine the saturated solubility of crystalline active pharmaceutical ingredient api in polymeric matrices directly during hot melt extrusion. Advantages of hot melt extrusion for the controlled. Objectives hot melt extrusion hme, which is a manufacturing technique, successfully used by the plastic and food industry since decades, gains increasing relevance for the development and production of pharmaceuticals. 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. Pur hot melt adhesives are great for bonds that require. Hot melt extrusion hme has been employed to prepare asd based products. Unlike other formulation options, hot melt extrusion technology is solvent free. Hot melt extrusion has been shown to molecularly disperse poorly soluble drugs in a polymer carrier increasing dissolution rates and bioavailability. Several of these subprocesses are linked to the residence time distribution rtd of the material within the apparatus. Downstream processing from hotmelt extrusion towards. Mar 20, 2012 hot melt extrusion technology kurt kortokrax sales account manager thermo fisher scientific 2. 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.
Melt extrusion materials, technology and drug product. In developing an hme drug system, the glass transition and melting temperatures are critical factors. This paper introduces hot melt extrusion 15 hme as an alternative method to manufacture sugarstarchpellets. Hotmelt extrusion technique was first invented for the. By applying a shear stress or a shear strain on a free. Hme involves the mixing of a drug with one or more. 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. 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. So far, no attempt was made to explore the feasibility of preparing coamorphous drugamino acid formulations via hme. 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. Since the lipid forms the matrix it can influence the drug release of the api. Hme has proven to be a robust method of producing numerous drug delivery systems like modified, controlled and targeted drug delivery systems.
In this approach, we examine excipients that are amenable to hot melt extrusion, forming a suspension of cocrystal particulates embedded in a pharmaceutical matrix. The process is useful for poorly soluble drugs and for alternative dosage forms such as controlledrelease drug devices. For hot melt extrusion, this selection process can start with a microscale performance evaluation on a hot stage microscope hsm. It was the researchers goal to prepare a dosage form in a simple and continuous manner. Pdf coupling 3d printing with hotmelt extrusion to. Optimelt is catalents unique ability to formulate, develop and commercialize hot melt extrusion processes and integrate these into differentiated final dosage forms. Hot melt extrusion hme, one leading technology for the preparation of amorphous drugpolymer formulations, provides the opportunity to prepare coamorphous formulations in a larger scale in a solvent free and continuous process. Processtechnologyofhotmelt extrusionhme hotmelt extrusion technique was. Thermal degradation was recognized as a limitation of this hot melt process. Hot melt extrusion techniques are pragmatic in the manufacture of a variety of dosage forms and formulations such as granules, pellets, tablets, suppositories, implants, stents, transdermal. Hme manufacture of amorphous dispersion involves the melting of a drug substance with an appropriate polymeric excipient in a corotating twinscrew extruder.
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 mississippi. Barrel temperature settings these are the temperatures set on the control instruments essential to reaching a desired melt temperature. 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. Processtechnologyofhot melt extrusion hme hot melt extrusion technique was.
Hot melt extrusion and spray drying of coamorphous. The role of polymer excipients in hot melt extrusion a. 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. Hot melt extrusion manufacturing process melt extrusion is an excellen t process to formulate poorly soluble drugs and to improve bioavailability advantages vs spray drying continuous process choice of an appropriate polymer is crucial for the formulation and the process most important polymer features aretg and melt viscosity. Furthermore, the use of reverseconveying and forwardconveying elements, kneading blocks and other intricate designs as. 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. Downstream processing from hotmelt extrusion towards tablets. This pur glue gun allows you to safely dispense pur hot melt.
Hotmelt extrusion of sugarstarchpellets pdf free download. In this respect, the technology competes directly with spray drying and may offer advantages in terms of cost and throughput. The formation or entrapment of rbubbles in the molten polymer during its extrusion can result in a nonhomogeneous product having unsatisfactory properties of strength. Polymeric formulations for drug release prepared by hot melt extrusion the quality of the final products. View hot melt extrusion research papers on academia. Rational development of solid dispersions via hotmelt. Hot melt extrusion hme is a promising technology for the production of new chemical. Hme is wellknown, developed to produce polymer products of uniform shape and density, and its industrial application dates back to the 1930s1. 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. 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. Generally, carbonbased rubber nanocomposites can be prepared via solutionmixing, latex blending, melt mixing, and hot melt extrusion. Formulation overview of common excipients and their designed functions.
However, due to the narrow processing window of hme, asds are normally obtained with high processing temperatures and mechanical stress. Rheological behavior of the polymer depends largely upon temperature, process history and pressure. In this chapter, the hotmelt extrusion to date hme has emerged as a novel. Hot melt extrusion in the pharmaceutical and food industries. A greater degree of conveying and much shorter residence times are achievable with an intermeshing setup. The extrudability of a polymer is mainly determined by t g or t m and melt viscosity. By drawing on continuous processing, hot melt extrusion is more economical and can be used for abuse deference and taste masking applications. Pdf hotmelt extrusion is one of the most widely applied processing technologies in the plastic, rubber and food industry. 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. Hot melt extrusion hme using twinscrew extruders tses is increasingly being used to make solid dispersions of drugs in a polymer matrix. 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. In brief, the extrusion conditions were used for the implants as following. Amorphous solid dispersions asds are commonly used in the pharmaceutical industry to improve the dissolution and bioavailability of poorly watersoluble drugs. Pdf hotmelt extrusion hme is a promising technology for the production of.
In melt mixing and hot melt extrusion, it is difficult to disperse the carbon nanofillers because of the high viscosity due to the high molecular weight of rubber. 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. The main objective of this work was to explore the potential of coupling fused deposition modeling in threedimensional 3d printing with hot melt extrusion hme technology to facilitate. Coating a host of factors can influence successful tablet coating. Hot melt extrusion is also utilized in pharmaceutical solid oral dose processing to enable delivery of drugs with poor solubility and bioavailability. Schippers method and apparatus for hot melt extrusion filed nov. Pdf hot melt extrusion is one of the most widely applied processing technologies in the plastic, rubber and food industry. Hotmelt extrusion is one of the most widely applied processing technologies in the plastic, rubber and food. Pdf pharmaceutical applications of hotmelt extrusion. Polyvinyl alcohol in hot melt extrusion to improve the. Hotmelt extrusion technique was first invented for the manufacturing of lead pipes at.
Once an extruder is up and running, most of the heat input required for extrusion is. We produce excipients and active ingredients of outstanding quality and performance. What is melt extrusion and how does it help us make new. Over the last three decades industrial adaptability has allowed hot melt extrusion hme to gain wide acceptance and has already established its place in the broad spectrum of manufacturing operations and pharmaceutical research developments. The main benefit of this process technology is the combination of different unit operations.
Hot melt extrusion hme is a proven technology for bioavailability enhancement of poorly soluble apis. Hot melt extrusion process the hot melt extrusion integrates the conventional methods of melting, mixing, kneading, venting and extrusion. Rheological data obtained during an extrusion process can provide information on the macromolecular structure of the melt and its morphology. Hot melt extrusion hme is a wellaccepted and extensively studied method for preparing numerous types of drug delivery systems and dosage forms. Pharmaceutics free fulltext inline determination of. In this context, twinscrew extrusion tse processes, such as hot melt extrusion hme, are one key aspect of current research. 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. The continuous nature of a hot melt extruder lends itself to a continuous production line. Hot melt extrusion hme is an efficient technology for producing solid molecular dispersions with considerable advantages including the absence of solvents, few processing steps, continuous. Pharmaceutics free fulltext influence of carbamazepine.
Pdf the advent of high throughput screening in the drug discovery process has. 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. B ecause hot melt extrusion hme is still a relatively new process for the pharmaceutical industry, it is more often used for formulation development than in the production environment. Scaleup challenges in hotmelt extrusion pharmaceutical. Polymers for hotmelt extrusion must exhibit thermoplastic characteristics and must be thermally stable at the proper extrusion temperature. Polyvinyl alcohol in hot melt extrusion to improve the solubility of drugs mengyao zheng, finn bauer, gudrun birk, dieter lubda 1 methods poorly watersoluble apis classified as biopharmaceutics classification system bcs ii class with different thermo properties were. Effective delivery of many of bcs class ii compounds with low solubility can be enabled with amorphous dispersions made by hot melt extrusion hme. Sincethen,ithasbeenusedintheplastic,rubber, and food manufacturing industry to produce items ranging from pipes to sheets and bags. Hot melt extrusion is a manufacturing technique that was originally established in the early 1930s for use in the plastics and food industries but is now gaining popularity in the pharmaceutical industry as well. Hot melt extrusion hme is the process of applying heat and pressure to melt a polymer and forcing it through an oriice in a continuous process. Today, hme is an accepted process for creating solid dispersions of apis. 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. Mechanochemical synthesis of pharmaceutical cocrystal.
The solubility of a model compound, paracetamol, in two polymer systems. Extruders provide extensive mixing and agitation that causes deaggregation of the suspended particles in the molten polymer resulting in a uniform dispersion. A batch size of 400 mg can provide sufficient materials to assess the drug product attributes such as solidstate properties, solubility enhancement, and physical stability as well as process related attributes such. Hotmelt extrusion by dennis douroumis overdrive rakuten. University of groningen innovative platform technologies. Pam buehnen 700kd glue gun overview the hb 700kd extrusion pur glue gun is a state of the art created by pam buehnen. Hot melt extrusion hot melt extrusion hme is the process of embedding an active pharmaceutical ingredient api in a polymeric. Use of terahertzraman spectroscopy to determine solubility.
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