The objective of this doctoral thesis was to evaluate the use of several nonconventional polymers as matrix excipients for hot melt extruded oralrelease formulations. Effective delivery of many of bcs class ii compounds with low solubility can be enabled with amorphous dispersions made by hotmelt extrusion hme. 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. It offers an overview of basf s polymers, more realworld application data and. Abstract the objective of this doctoral thesis was to evaluate the use of several nonconventional polymers as matrix excipients for hot melt extruded oralrelease formulations. Polymers for hot melt extrusion must exhibit thermoplastic characteristics and must be thermally stable at the proper extrusion temperature. The biggest challenge for the application of hme is the thermal degradation of drug, poor physical stability of asd and precipitation of drug during dissolution.
Improved mesalamine release by hotmelt extrusion hme technique could be utilized for better management of inflammatory bowel disease ibd. Bioavailability enhancement using hot melt extrusion basf. Comparison between hotmelt extrusion and spraydrying for. Hot melt extrusion hme as a technique for producing amorphous solid dispersion asd has been widely used in pharmaceutical research. 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. The role of polymer excipients in hot melt extrusion a. Solid dispersions by hotmelt extrusion pharmaceutical. Three dimensional 3d printing as an advanced manufacturing technology is progressing to be established in the pharmaceutical industry to overcome the traditional manufacturing regime of one. Suitability of pure and plasticized polymers for hot melt. Polymeric formulations for drug release prepared by hot melt. By drawing on continuous processing, hot melt extrusion is more economical and can be used for abuse deference and taste masking applications.
Melt extrusion materials, technology and drug product. Polymers for hotmelt extrusion must exhibit thermoplastic characteristics and must be thermally stable at the proper extrusion temperature. Today we solve unmet formulation needs and offer intelligent solutions for today and tomorrows challenges in drug formulation. Formulation and characterization of solid dispersion. Hot melt extrusion hotmelt extrusion hme is used for blending, melting, extrusion and shaping in a single step process. Pharmaceutics free fulltext polymers for extrusion. Hotmelt extruded filaments based on pharmaceutical grade polymers for 3d printing by fused deposition modeling.
In developing an hme drug system, the glass transition and. Polymeric formulations for drug release prepared by hot. Useful for understanding hotmelt extrusion technology and principles. Scale up of a hot melt extrusion process andreas gryczke basf. A systematic stepbystep approach is presented, where thermodynamics, polymer screening, multivariate statistics and process optimization are combined, to increase the success of hmebased drug product development. The interest in hotmelt extrusion has increased rapidly in the pharmaceutical industry during the last years which has led to a demand in.
Provide on the one hand an efficient screening tool for hotmelt extrusion hme formulation development and make available on the other. Interactions between drugs and polymers influencing hot. Compared with other pharmaceutical technologies, such as granulation and compression, hot melt extrusion is still an emerging method, and its potential has not been explored fully yet. Pharmaceutics free fulltext polymers for extrusionbased. Prior to joining basf he worked for croda international in uk, japan and usa. Overallapplicationsofhme extrusion technology is one of the most important fabrication processes in the plastic and rubber industries. However, as with other innovations, numerous obstacles have to be overcome before the technology and resulting dosage forms can be exploited commercially. One major advantage is the fact that no solvents are required. Mes and hydrophilic polymers like eudragit epo, kollidonva64 and peg 6000 were hot melt extruded using a corotating twinscrew laboratory extruder. Author bart claeys ugent promoter chris vervaet ugent and jean paul remon ugent organization. Hot melt extrusion hme is a proven technology for bioavailability enhancement of poorly soluble apis. The sulindacpolymerplasticizer combination that was stable with good film forming properties was processed by hot melt mixing, a technique close to hot melt extrusion, to predict its behavior in a hot.
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. Writers aliaune thiam, gwen stefani, giorgio tuinfort, akon. Polymeric formulations for drug release prepared by hot melt extrusion 1. Here the use of the spraydried copolymer did not show any benefit concerning the kinetic miscibility of the drug and copolymer.
Extruders provide extensive mixing and agitation that causes deaggregation of the suspended particles in the molten polymer resulting in a uniform dispersion. Dec 11, 2010 basf has now published the first compendium on hot melt extrusion, a method that is being increasingly used in the pharmaceutical industry to help an active drug substance to dissolve properly in the stomach and provide more effective treatment. Temperature and moisture activated drugpolymer interactions for enhanced stability. 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.
Dec 11, 20 hot melt extrusion hme as a technique for producing amorphous solid dispersion asd has been widely used in pharmaceutical research. Products made from melt extruded polymers range from. One major advantage is the fact that no solvents are. 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. Today, hme is an accepted process for creating solid dispersions of apis. The biggest challenge for the application of hme is. Hot melt extrusion for amorphous solid dispersions. Hot melt extrusion is the new mixer extrusion range that builds on the proven umang technology and its benefits.
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. Pdf pharmaceutical applications of hotmelt extrusion. Hot melt extrusion with basf pharma polymers extrusion compendium 2nd revised and enlarged edition k. Hotmelt extrusion with basf pharma polymers extrusion compendium 2nd revised and enlarged edition k. We produce excipients and active ingredients of outstanding quality and performance. A systematic stepbystep approach is presented, where thermodynamics, polymer. Extrusion compendium 2nd revised and enlarged edition 2012. Polymers are the key materials that are necessary for 3d. Review and cite hot melt extrusion protocol, troubleshooting and other methodology information contact experts in hot melt extrusion to get answers. University of groningen innovative platform technologies.
In the 1980s, basf became the first company to apply it to the production of pharmaceuticals for enhancing the solubility. Hotmelt extrusion resulted in an even higher mixing capability. Investigation of pharmaceutical hotmelts via simultaneous. Interest in hot melt extrusion techniques for pharmaceutical applications is growing rapidly with well over 100 papers published in the pharmaceutical scientific literature in the last 12 years. Using 3d printing, it is possible to design and develop complex dosage forms that can be suitable for tuning drug release. It offers an overview of basf s polymers, more realworld application. Interest in hotmelt extrusion techniques for pharmaceutical applications is growing rapidly with well over 100 papers published in the pharmaceutical scientific literature in the last 12 years. Through science and innovation we provide our customers with products to meet the current and future needs of business and society. In drug discovery and development, industry estimates that more than 50% of. Improved mesalamine release by hot melt extrusion hme technique could be utilized for better management of inflammatory bowel disease ibd. As introduced, the compendium contains practical instructions for use and extensive descriptions of all the relevant. It offers an overview of basf s polymers, more realworld application data and factors to consider in the formulation process. 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.
Hme has already been demonstrated as a robust, novel technique to make solid dispersions in order to provide time controlled, modified, extended, and. Williams iii 1, 1 molecular pharmaceutics and drug delivery, college of pharmacy, the university of texas at austin, 2409 university avenue, austin, tx. 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. Leveraging hot melt extrusion for solubility and continuous. In developing an hme drug system, the glass transition and melting temperatures are critical factors. This paper presents a novel onestep process for converting a liquid stabilized nanosuspension into a solid formulation via hotmelt extrusion combined with an internal devolatilization. Basf publishes first hot melt extrusion compendium plastics. 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. The extrudability of a polymer is mainly determined by t g or t m and melt viscosity. Hme is also a continuous process, which has been encouraged by the fda.
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. You can find detailed information on our product range by looking up your industry or using our product finder. Nonconventional polymers as matrix excipients for hot. 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. Nir and raman for hme lien saerens seps pharma, gent, belgium workshop explanation and group assignment workshops session ii. Basf has been committed to the pharmaceutical industry since we introduced our original kollidon in the early 20th century. Hot melt extrusion system for pharmaceutical applications. Hot melt extruded filaments based on pharmaceutical grade polymers for 3d printing by fused deposition modeling. Unlike other formulation options, hot melt extrusion technology is solventfree. Hot melt extrusion hot melt extrusion hme is used for blending, melting, extrusion and shaping in a single step process. Three dimensional 3d printing as an advanced manufacturing technology is progressing to be established in the pharmaceutical industry to overcome the traditional manufacturing regime of one size fits for all. Nov 23, 2010 hot melt extrusion resulted in an even higher mixing capability. Hot melt extrusion hme technology has become a key solution to adding absorption for enhanced solubility. Our affinisol polymers are specifically tailored to address the solubilization performance requirements of your apis.
Pharmaceutical applications is an essential multidisciplinary guide to the emerging pharmaceutical uses of this processing technology for researchers in academia and industry working. Solid dispersions can be obtained using different processes. Introduction since the 1930s, hot melt extrusion hme has found its place as an established process in the plastic and food. 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. 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. The new edition provides readers with an even better understanding of solid dispersions and the hotmelt extrusion process. Hotmelt extruded filaments based on pharmaceutical grade. Our affinisol polymers are specifically tailored to address the solubilization performance requirements of your apis, whether you have chosen to formulate via spraydried dispersion sdd or hot melt extrusion hme. You can find detailed information on our product range by looking up. Basf has now published the first compendium on hot melt extrusion, a method that is being increasingly used in the pharmaceutical industry to help an active drug substance to dissolve. Interactions between drugs and polymers influencing hot melt.
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. Since then we have continuously expanded our solution offer. Polymeric formulations for drug release prepared by hot melt extrusion. The barrel had ten sections barrel zones, which were individually heated with electric heaters. 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. The temperatures of the individual barrels were in a range of 100150c. Nonconventional polymers as matrix excipients for hot melt. Hot melt extruder pharmaceutical machine manufacturers and. Basf publishes first hot melt extrusion compendium.
842 258 405 942 321 922 152 1226 1227 846 182 159 1464 407 1200 1167 1397 1184 466 1559 420 1434 682 1511 967 34 938 663 1565 111 1297 1311 1576 678 1566 222 271 584 1274 384 672 1122 218 640 1141 226 79 1332 1105