Cookies help us deliver our services. By using our services, you agree to our use of cookies. Learn more.

    Bioavailability enhancement using hot melt extrusion



    Hot-melt extrusion for enhanced solubility and bioavailability

    Hot-melt extrusion has been used in the plastics & food industries for decades. 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. Today, HME is an accepted process for creating solid dispersions of APIs.

    The solubility and bioavailability of poorly soluble APIs is often enhanced when they are molecularly dispersed in a polymeric carrier. This makes hot melt extrusion (HME) a valuable technology for the pharmaceutical industry – and opens new doors for formulators working with promising actives that cannot otherwise be solubilized. HME also grants manufacturers a great amount of flexibility, as the viscous fluid obtained from the extrusion process can be directly shaped into any desired form. In addition, the extrudates usually have a high density, which makes them suitable for producing controlled-release dosage forms.

    Outstanding range of functional solutions. Uncompromising quality.
    Innovative and cost-effective drug delivery
    Enhanced bioavailability and controlled release
    Customer-specific solutions and global support

    Our aim is to help our customers discover the many benefits of this technology, and assist them in leveraging it for their products. The true potential of hot-melt extrusion for pharmaceutical applications is just beginning to be uncovered – and our research continues to blaze new trails in this exciting field.

    The hot-melt extrusion process at a glance

    In the pharmaceutical industry, hot-melt extrusion is used to prepare solid dispersions of poorly soluble active pharmaceutical ingredients, and for creating controlled-release medications. In this process, active ingredients are compounded with polymers that have suitable glass transition temperatures (such as Soluplus®), and extruded at an appropriate temperature to form a solid dispersion. This polymer matrix acts as a solid solvent for the drug molecules. The API can be amorphous, molecularly dispersed or crystalline dispersed within the polymer – depending on the application. The extrudate is suitable for direct shaping, granules, spheres, powders, films, patches, and injections.

    Using hot-melt extrusion to produce solid dispersions

    To transform an API into its amorphous form, it is necessary to overcome its crystal lattice energy. Afterwards, the API is blended with a polymer and co-dispersed. Both steps take place in an extruder. First, the crystalline API and the amorphous polymer are fed into the extruder, before being conveyed and exposed to shear stress. The resulting dispersion (referred to as extrudate) is then pressed out and collected for further processing. For more information, please see the second edition of our Hot-Melt Extrusion Compendium.

    BASF functional excipients for hot-melt extrusion

    To prepare a solid dispersion, the active ingredient must be embedded in a matrix. If the matrix cannot sufficiently solubilize the active ingredient solubilizers must be added. Soluplus exhibits both matrix-forming and solubilization properties – making it ideal for such cases. If the extrusion process temperature is below 100° C, a plasticizer may also be necessary. This is particularly important in cases where the active ingredient is processed without melting, i.e. where it cannot act as a plasticizing agent.

    Dissolution enhancers are the fourth component of solid dispersions. They are usually added because low-porosity solid dispersions prepared via HME typically have limited disintegration capability.

    Hot Melt Extrusion Process

    Solubilization Platform

    Effective solubilization in solid & liquid dosage form.

    Hot melt extrusion & solubilizer compendia by BASF

    BASF Hot Melt Extrusion compendium 2nd edition

    Hot melt extrusion with BASF Pharma Polymers

    Extrusion Compendium 2nd and enlarged edition.

    BASF Solubilization Compendium

    Solubility Enhancement with BASF Pharma Polymers

    Solubilizer Compendium.

    Brochure

    New formulas for successful drug delivery - Hot-melt extrusion for enhanced solubility and bioavailability

    New formulas for successful drug delivery - Hot-melt extrusion for enhanced solubility and bioavailability

    Webinars

    Choosing the Proper Dissolution Method When Testing Solubilization Performance

    With the increase in use of advanced formulation methods to improve solubility of drugs, standard dissolution methods are not always capable to reflect the full in-vivo potential. This webinar will take a close look at dissolution testing of solid dispersions made with polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (Soluplus®) and how to design an appropriate dissolution test that is discriminatory for APIs with different prerequisites. Standard compendial dissolution tests do not necessarily reflect the actual performance potential of solid dispersions in terms of later bioavailability due to their simplistic setup. This webinar will focus on a workflow to find the proper dissolution test for solid dispersions, using a Soluplus-based formulation as an example. The target is to show a methodology to have discriminating dissolution methods, which represent the expected performance ranking in-vivo among different formulations.

    How glass-forming polymers improve bioavailability / Enhanced oral bioavailability with Soluplus® – case study

    How glass-forming polymers improve bioavailability Polymers are essential components of oral solid dosage forms and used as binders, disintegrants or coatings. Given the increase in poorly water-soluble drugs, not only well-known but also specifically designed polymers (e.g. Soluplus®) can be used to improve both drug dissolution and bioavailability. Solid dispersions – embedded drug molecules at a molecularly dispersed state into an amorphous polymer – have shown superior bioavailability in comparison to other drug delivery systems. This webinar introduces the specific process technologies, namely hot melt extrusion or spray-drying, and the polymeric excipients available in the BASF portfolio to develop stable solid solutions. Enhanced oral bioavailability with Soluplus® – case study Soluplus® based solid solutions increase the solubility and oral bioavailability of poorly soluble active ingredients. Results from an in-vivo study in dogs with itraconazole showed a more than two-fold increase in oral bioavailability of a Soluplus® based formulation compared to the commercially available drug product. The Presentation explains what is special about Soluplus® and gives recommendations for in-vitro dissolution testing and the formulation of a quickly disintegrating tablet.

    Articles

    European Journal of Pharmaceutics and Biopharmaceutics

    Predicting melt rheology for hot-melt extrusion by means of a simple Tg-measurement

    The feasibility of predicting melt rheology by using the glass transition temperature (Tg) of a desired amorphous solid dispersion (ASD) for hot-melt extrusion (HME) and other melt based processes is presented.

    European Journal of Pharmaceutics and Biopharmaceutics

    Micro-scale prediction method for API-solubility in polymeric matrices

    A new predictive micro-scale solubility and process model for amorphous solid dispersions (ASDs) by hot-melt extrusion (HME) is presented.

    Combining HME & Solubilization: Soluplus® - The Solid Solution (Excipient Update – Drug Delivery Technology)

    Drug solubilization has drawn attention in recent years because large numbers of NCEs often fail in development due to their poor solubility and bioavailability. Hot melt extrusion (HME) has gained a significant interest in recent years. Even though this technique has been used in plastics and food industries for decades, it is relatively new in the pharmaceutical industry, and only a few drug products (based on polyethylene glycol or copovidone) are currently available on the market. BASF has introduced a new polymeric solubilizer, Soluplus ®, a graft copolymer composed of polyethylene glycol, polyvinylcaprolactam, and polyvinylacetate.

    The advantages and disadvantages of hot-melt extrusion in solid dispersion formulations

    Solid dispersions represent a promising formulation approach for overcoming today's major challenge in pharmaceutical formulation development: poorly soluble and poorly permeable active pharmaceutical ingredients (APIs). Solid dispersions can be obtained using different processes; however, hot-melt extrusion (HME) is extremely suitable for this purpose.

    AAPS PharmSci Tech

    Design and Evaluation of Topical Diclofenac Sodium Gel Using HME as a Continuous Manufacturing Process with Kolliphor ® P407

    The aim of the present context was to develop and evaluate a Kolliphor ® P407-based transdermal gel formulation of diclofenac sodium by hot melt extrusion (HME) technology; central composite design was used to optimize the formulation process. In this study, we have explored first time ever HME as an industrially feasible and continuous manufacturing technology for the manufacturing of gel formulation using Kolliphor ® P407 and Kollisolv ® PEG400 as a gel base.

    Bioavailability Enhancement - A Soluplus® case study of itraconazole

    The advantages and disadvantages of hot-melt extrusion in solid dispersion formulations.

    Podcasts

    Whitepapers

    Twin Screw Wet Granulation for Solubility Enhancement of Poorly Water-Soluble Drugs

    Poorly-soluble APIs present formulation and development challenges. Excipient selection and manufacturing process development are crucial. Continuous twin-screw granulation is gaining acceptance as a manufacturing technology to address issues presented by these APIs and is offering high production capacity in a small footprint. In this dedicated dialogue, solubility enhancement expert Andreas Gryczke from BASF will answer additional questions that have been posed in our recent webinar on Twin Screw Wet Granulation for Solubility Enhancement of Poorly Water-Soluble Drugs.

    Choosing the Proper Dissolution Method when Testing Solubilization Performance of Poorly Soluble Drug Molecules

    With the increase in use of advanced formulation methods to improve solubility of drugs, standard dissolution methods are not always capable to reflect the full in-vivo potential. This whitepaper will take a close look at dissolution testing of solid dispersions made with polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (Soluplus®) and how to design an appropriate dissolution test that is discriminatory for APIs with different prerequisites.

    Video