Pharmaceutics

Editorial

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3 pages, 152 KiB

Open AccessEditorial

Pharmaceutical Applications of Hot-Melt Extrusion: Continuous Manufacturing, Twin-Screw Granulations, and 3D Printing

by Mohammed Maniruzzaman

Pharmaceutics 2019, 11(5), 218; https://doi.org/10.3390/pharmaceutics11050218 - 7 May 2019

Cited by 16 | Viewed by 4898

Abstract

Recently, hot-melt extrusion (HME) techniques have been presented as innovative platforms to produce various pharmaceuticals [...] Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Hot-melt Extrusion)

Research

Jump to: Editorial, Review

20 pages, 7853 KiB

Open AccessArticle

Modelling the Effect of Process Parameters on the Wet Extrusion and Spheronisation of High-Loaded Nicotinamide Pellets Using a Quality by Design Approach

by Eva-Maria Theismann, Julia K. Keppler, Martin Owen, Karin Schwarz and Walkiria Schlindwein

Pharmaceutics 2019, 11(4), 154; https://doi.org/10.3390/pharmaceutics11040154 - 1 Apr 2019

Cited by 8 | Viewed by 4769

Abstract

The aim of the present study was to develop an alternative process to spray granulation in order to prepare high loaded spherical nicotinamide (NAM) pellets by wet extrusion and spheronisation. Therefore, a quality by design approach was implemented to model the effect of [...] Read more.

The aim of the present study was to develop an alternative process to spray granulation in order to prepare high loaded spherical nicotinamide (NAM) pellets by wet extrusion and spheronisation. Therefore, a quality by design approach was implemented to model the effect of the process parameters of the extrusion-spheronisation process on the roundness, roughness and useable yield of the obtained pellets. The obtained results were compared to spray granulated NAM particles regarding their characteristics and their release profile in vitro after the application of an ileocolon targeted shellac coating. The wet extrusion-spheronisation process was able to form highly loaded NAM pellets (80%) with a spherical shape and a high useable yield of about 90%. However, the water content range was rather narrow between 24.7% and 21.3%. The design of experiments (DoE), showed that the spheronisation conditions speed, time and load had a greater impact on the quality attributes of the pellets than the extrusion conditions screw design, screw speed and solid feed rate (hopper speed). The best results were obtained using a low load (15 g) combined with a high rotation speed (900 m/min) and a low time (3–3.5 min). In comparison to spray granulated NAM pellets, the extruded NAM pellets resulted in a higher roughness and a higher useable yield (63% vs. 92%). Finally, the coating and dissolution test showed that the extruded and spheronised pellets are also suitable for a protective coating with an ileocolonic release profile. Due to its lower specific surface area, the required shellac concentration could be reduced while maintaining the release profile. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Hot-melt Extrusion)

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25 pages, 9358 KiB

Open AccessArticle

In-Line UV-Vis Spectroscopy as a Fast-Working Process Analytical Technology (PAT) during Early Phase Product Development Using Hot Melt Extrusion (HME)

by Walkiria Schlindwein, Mariana Bezerra, Juan Almeida, Andreas Berghaus, Martin Owen and Gordon Muirhead

Pharmaceutics 2018, 10(4), 166; https://doi.org/10.3390/pharmaceutics10040166 - 23 Sep 2018

Cited by 23 | Viewed by 8490

Abstract

This paper displays the potential of an in-line PAT system for early phase product development during pharmaceutical continuous manufacturing following a Quality by Design (QbD) framework. Hot melt extrusion (HME) is used as continuous manufacturing process and UV–Vis spectroscopy as an in-line monitoring [...] Read more.

This paper displays the potential of an in-line PAT system for early phase product development during pharmaceutical continuous manufacturing following a Quality by Design (QbD) framework. Hot melt extrusion (HME) is used as continuous manufacturing process and UV–Vis spectroscopy as an in-line monitoring system. A sequential design of experiments (DoE) (screening, optimisation and verification) was used to gain process understanding for the manufacture of piroxicam (PRX)/Kollidon^® VA64 amorphous solid dispersions. The influence of die temperature, screw speed, solid feed rate and PRX concentration on the critical quality attributes (CQAs) absorbance and lightness of color (L*) of the extrudates was investigated using multivariate tools. Statistical analysis results show interaction effects between concentration and temperature on absorbance and L* values. Solid feed rate has a significant effect on absorbance only and screw speed showed least impact on both responses for the screening design. The optimum HME process conditions were confirmed by 4 independent studies to be 20% w/w of PRX, temperature 140 °C, screw speed 200 rpm and feed rate 6 g/min. The in-line UV-Vis system was used to assess the solubility of PRX in Kollidon^® VA64 by measuring absorbance and L* values from 230 to 700 nm. Oversaturation was observed for PRX concentrations higher than 20% w/w. Oversaturation can be readily identified as it causes scattering in the visible range. This is observed by a shift of the baseline in the visible part of the spectrum. Extrudate samples were analyzed for degradation using off-line High-Performance Liquid Chromatography (HPLC) standard methods. Results from off-line experiments using differential scanning calorimetry (DSC), and X-ray diffraction (XRD) are also presented. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Hot-melt Extrusion)

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15 pages, 2895 KiB

Open AccessArticle

Validation of Model-Based Melt Viscosity in Hot-Melt Extrusion Numerical Simulation

by Esther S. Bochmann, Andreas Gryczke and Karl G. Wagner

Pharmaceutics 2018, 10(3), 132; https://doi.org/10.3390/pharmaceutics10030132 - 18 Aug 2018

Cited by 13 | Viewed by 4902

Abstract

A validation for the use of model-based melt viscosity in hot-melt extrusion numerical simulations was presented. Here, the melt viscosity of an amorphous solid dispersion (ASD) was calculated by using its glass transition temperature (T_g) and the rheological flow profile [...] Read more.

A validation for the use of model-based melt viscosity in hot-melt extrusion numerical simulations was presented. Here, the melt viscosity of an amorphous solid dispersion (ASD) was calculated by using its glass transition temperature (T_g) and the rheological flow profile of the pure polymeric matrix. All further required physical properties were taken from the pure polymer. For forming the ASDs, four active pharmaceutical ingredients (APIs), that had not been considered in first place to establish the correlation between T_g and melt viscosity were examined. The ASDs were characterized in terms of density, specific heat capacity, melt rheology, API solubility in the polymeric matrix, and deviation from the Couchman–Karasz fit to, identify the influencing factors of the accuracy of the simulation using model-based melt viscosity. Furthermore, the energy consumption of the hot-melt extrusion (HME) experiments, conventional simulation, and simulation using model-based melt viscosity were compared. It was shown, with few exceptions, that the use of model-based melt viscosity in terms of the HME simulation did not reduce the accuracy of the computation outcome. The commercial one-dimensional (1D) simulation software Ludovic^® was used to conduct all of the numerical computation. As model excipients, vinylpyrrolidone-vinyl acetate copolymer (COP) in combination with four APIs (celecoxib, loratadine, naproxen, and praziquantel) were investigated to form the ASDs. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Hot-melt Extrusion)

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25 pages, 8605 KiB

Open AccessArticle

Twin Screw Granulation: Effects of Properties of Primary Powders

by Sushma V. Lute, Ranjit M. Dhenge and Agba D. Salman

Pharmaceutics 2018, 10(2), 68; https://doi.org/10.3390/pharmaceutics10020068 - 2 Jun 2018

Cited by 21 | Viewed by 8669

Abstract

Lactose and mannitol are some of the most commonly used powders in the pharmaceutical industry. The limited research published so far highlights the effects of process and formulation parameters on the properties of the granules and the tablets produced using these two types [...] Read more.

Lactose and mannitol are some of the most commonly used powders in the pharmaceutical industry. The limited research published so far highlights the effects of process and formulation parameters on the properties of the granules and the tablets produced using these two types of powders separately. However, the comparison of the performance of these two types of powders during twin screw wet granulation has received no attention. The present research is focused on understanding the granulation mechanism of different grades of two pharmaceutical powders with varying properties (i.e., primary particle size, structure, and compressibility). Three grades each of lactose and mannitol were granulated at varying liquid to solid ratios (L/S) and screw speed. It was noticed that primary powder morphology plays an important role in determining the granule size and structure, and tablet tensile strength. It was indicated that the processed powders such as spray-dried and granulated lactose and mannitol can be used in formulation for wet granulation where flowability of active pharmaceutical ingredient (API) is poor. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Hot-melt Extrusion)

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21 pages, 6403 KiB

Open AccessArticle

Twin Screw Granulation: An Investigation of the Effect of Barrel Fill Level

by Sushma V. Lute, Ranjit M. Dhenge and Agba D. Salman

Pharmaceutics 2018, 10(2), 67; https://doi.org/10.3390/pharmaceutics10020067 - 1 Jun 2018

Cited by 39 | Viewed by 5968

Abstract

This paper focuses on investigating the influence of varying barrel fill levels on the mean residence time, granule properties (median size, size distribution, and shape), and tensile strength of tablets. Specific feed load (SFL) (powder feed rate divided by screw speed) and powder [...] Read more.

This paper focuses on investigating the influence of varying barrel fill levels on the mean residence time, granule properties (median size, size distribution, and shape), and tensile strength of tablets. Specific feed load (SFL) (powder feed rate divided by screw speed) and powder feed number (PFN) (i.e., powder mass flow rate divided by the product of screw speed, screw diameter, and the material density in the denominator) were considered as surrogates for the barrel fill level. Two type of powders (lactose and microcrystalline cellulose (MCC)) were granulated separately at varying fill levels at different liquid-to-solid ratios (L/S). It was observed that by controlling the barrel fill level, the granule size, shape, and tablet tensile strength can be maintained at specific L/S. It was also noticed that the mean residence time decreased with increasing fill levels in the case of both lactose and MCC powder. However, it was only found to be related to the change in granule size in case of granulating microcrystalline cellulose at varying fill levels. At very high fill levels, granule size decreased, owing to a limited interaction between MCC powder and liquid at high throughput force and short residence time. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Hot-melt Extrusion)

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20 pages, 5237 KiB

Open AccessArticle

A Repurposed Drug for Brain Cancer: Enhanced Atovaquone Amorphous Solid Dispersion by Combining a Spontaneously Emulsifying Component with a Polymer Carrier

by Hiroyuki Takabe, Zachary N. Warnken, Yajie Zhang, Daniel A. Davis, Hugh D. C. Smyth, John G. Kuhn, Steve Weitman and Robert O. Williams III

Pharmaceutics 2018, 10(2), 60; https://doi.org/10.3390/pharmaceutics10020060 - 19 May 2018

Cited by 22 | Viewed by 7981

Abstract

Glioblastoma multiforme (GBM) is the most common and lethal central nervous system tumor. Recently, atovaquone has shown inhibition of signal transducer and activator transcription 3, a promising target for GBM therapy. However, it is currently unable to achieve therapeutic drug concentrations in the [...] Read more.

Glioblastoma multiforme (GBM) is the most common and lethal central nervous system tumor. Recently, atovaquone has shown inhibition of signal transducer and activator transcription 3, a promising target for GBM therapy. However, it is currently unable to achieve therapeutic drug concentrations in the brain with the currently reported and marketed formulations. The present study sought to explore the efficacy of atovaquone against GBM as well as develop a formulation of atovaquone that would improve oral bioavailability, resulting in higher amounts of drug delivered to the brain. Atovaquone was formulated as an amorphous solid dispersion using an optimized formulation containing a polymer and a spontaneously emulsifying component (SEC) with greatly improved wetting, disintegration, dispersibility, and dissolution properties. Atovaquone demonstrated cytotoxicity against GBM cell lines as well as provided a confirmed target for atovaquone brain concentrations in in vitro cell viability studies. This new formulation approach was then assessed in a proof-of-concept in vivo exposure study. Based on these results, the enhanced amorphous solid dispersion is promising for providing therapeutically effective brain levels of atovaquone for the treatment of GBM. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Hot-melt Extrusion)

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25 pages, 11036 KiB

Open AccessArticle

A Miniaturized Extruder to Prototype Amorphous Solid Dispersions: Selection of Plasticizers for Hot Melt Extrusion

by Matthias E. Lauer, Reto Maurer, Anne T. De Paepe, Cordula Stillhart, Laurence Jacob, Rajesh James, Yuki Kojima, Rene Rietmann, Tom Kissling, Joost A. Van den Ende, Sabine Schwarz, Olaf Grassmann and Susanne Page

Pharmaceutics 2018, 10(2), 58; https://doi.org/10.3390/pharmaceutics10020058 - 19 May 2018

Cited by 13 | Viewed by 5648

Abstract

Hot-melt extrusion is an option to fabricate amorphous solid dispersions and to enhance oral bioavailability of poorly soluble compounds. The selection of suitable polymer carriers and processing aids determines the dissolution, homogeneity and stability performance of this solid dosage form. A miniaturized extrusion [...] Read more.

Hot-melt extrusion is an option to fabricate amorphous solid dispersions and to enhance oral bioavailability of poorly soluble compounds. The selection of suitable polymer carriers and processing aids determines the dissolution, homogeneity and stability performance of this solid dosage form. A miniaturized extrusion device (MinEx) was developed and Hypromellose acetate succinate type L (HPMCAS-L) based extrudates containing the model drugs neurokinin-1 (NK1) and cholesterylester transfer protein (CETP) were manufactured, plasticizers were added and their impact on dissolution and solid-state properties were assessed. Similar mixtures were manufactured with a lab-scale extruder, for face to face comparison. The properties of MinEx extrudates widely translated to those manufactured with a lab-scale extruder. Plasticizers, Polyethyleneglycol 4000 (PEG4000) and Poloxamer 188, were homogenously distributed but decreased the storage stability of the extrudates. Stearic acid was found condensed in ultrathin nanoplatelets which did not impact the storage stability of the system. Depending on their distribution and physicochemical properties, plasticizers can modulate storage stability and dissolution performance of extrudates. MinEx is a valuable prototyping-screening method and enables rational selection of plasticizers in a time and material sparing manner. In eight out of eight cases the properties of the extrudates translated to products manufactured in lab-scale extrusion trials. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Hot-melt Extrusion)

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15 pages, 3098 KiB

Open AccessArticle

Polymer–Surfactant System Based Amorphous Solid Dispersion: Precipitation Inhibition and Bioavailability Enhancement of Itraconazole

by Disang Feng, Tingting Peng, Zhengwei Huang, Vikramjeet Singh, Yin Shi, Ting Wen, Ming Lu, Guilan Quan, Xin Pan and Chuanbin Wu

Pharmaceutics 2018, 10(2), 53; https://doi.org/10.3390/pharmaceutics10020053 - 24 Apr 2018

Cited by 62 | Viewed by 8275

Abstract

The rapid release of poorly water-soluble drugs from amorphous solid dispersion (ASD) is often associated with the generation of supersaturated solution, which provides a strong driving force for precipitation and results in reduced absorption. Precipitation inhibitors, such as polymers and surfactants, are usually [...] Read more.

The rapid release of poorly water-soluble drugs from amorphous solid dispersion (ASD) is often associated with the generation of supersaturated solution, which provides a strong driving force for precipitation and results in reduced absorption. Precipitation inhibitors, such as polymers and surfactants, are usually used to stabilize the supersaturated solution by blocking the way of kinetic or thermodynamic crystal growth. To evaluate the combined effect of polymers and surfactants on maintaining the supersaturated state of itraconazole (ITZ), various surfactants were integrated with enteric polymer hydroxypropyl methylcellulose acetate succinate (HPMC AS) to develop polymer–surfactant based solid dispersion. The supersaturation stability was investigated by in vitro supersaturation dissolution test and nucleation induction time measurement. Compared to the ASD prepared with HPMC AS alone, the addition of d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) exhibited a synergistic effect on precipitation inhibition. The results indicated that the TPGS not only significantly reduced the degree of supersaturation which is the driving force for precipitation, but also provided steric hindrance to delay crystal growth by absorbing onto the surface of small particles. Subsequently, the formulations were evaluated in vivo in beagle dogs. Compared with commercial product Sporanox^®, the formulation prepared with HPMC AS/TPGS exhibited a 1.8-fold increase in the AUC (0–24 h) of ITZ and a 1.43-fold increase of hydroxyitraconazole (OH-ITZ) in the plasma. Similarly, the extent of absorption was increased by more than 40% when compared to the formulation prepared with HPMC AS alone. The results of this study demonstrated that the ASD based on polymer–surfactant system could obviously inhibit drug precipitation in vitro and in vivo, which provides a new access for the development of ASD for poorly water-soluble drug. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Hot-melt Extrusion)

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10 pages, 10899 KiB

Open AccessArticle

Inline Determination of Residence Time Distribution in Hot-Melt-Extrusion

by Jens Wesholowski, Andreas Berghaus and Markus Thommes

Pharmaceutics 2018, 10(2), 49; https://doi.org/10.3390/pharmaceutics10020049 - 15 Apr 2018

Cited by 31 | Viewed by 6690

Abstract

In the framework of Quality-by-Design (QbD), the inline determination of process parameters or quality attributes of a product using sufficient process analytical technology (PAT) is a center piece for the establishment of continuous processes as a standard pharmaceutical technology. In this context, Twin-Screw-Extrusion [...] Read more.

In the framework of Quality-by-Design (QbD), the inline determination of process parameters or quality attributes of a product using sufficient process analytical technology (PAT) is a center piece for the establishment of continuous processes as a standard pharmaceutical technology. In this context, Twin-Screw-Extrusion (TSE) processes, such as Hot-Melt-Extrusion (HME), are one key aspect of current research. The main benefit of this process technology is the combination of different unit operations. Several of these sub-processes are linked to the Residence Time Distribution (RTD) of the material within the apparatus. In this study a UV/Vis spectrophotometer from ColVisTec was tested regarding the suitability for the inline determination of the RTD of an HME process. Two different measuring positions within a co-rotating Twin-Screw-Extruder were compared to an offline HPLC–UV as reference method. The obtained results were overall in good agreement and therefore the inline UV/Vis spectrophotometer is suitable for the determination of the RTD in TSE. An influence of the measuring position on repeatability was found and has to be taken into consideration for the implementation of PATs. An effect of the required amount of marker on process rheology is not likely due to the low Limit-of-Quantification (LoQ). Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Hot-melt Extrusion)

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27 pages, 60906 KiB

Open AccessArticle

Material Considerations for Fused-Filament Fabrication of Solid Dosage Forms

by Evert Fuenmayor, Martin Forde, Andrew V. Healy, Declan M. Devine, John G. Lyons, Christopher McConville and Ian Major

Pharmaceutics 2018, 10(2), 44; https://doi.org/10.3390/pharmaceutics10020044 - 2 Apr 2018

Cited by 117 | Viewed by 11485

Abstract

Material choice is a fundamental consideration when it comes to designing a solid dosage form. The matrix material will ultimately determine the rate of drug release since the physical properties (solubility, viscosity, and more) of the material control both fluid ingress and disintegration [...] Read more.

Material choice is a fundamental consideration when it comes to designing a solid dosage form. The matrix material will ultimately determine the rate of drug release since the physical properties (solubility, viscosity, and more) of the material control both fluid ingress and disintegration of the dosage form. The bulk properties (powder flow, concentration, and more) of the material should also be considered since these properties will influence the ability of the material to be successfully manufactured. Furthermore, there is a limited number of approved materials for the production of solid dosage forms. The present study details the complications that can arise when adopting pharmaceutical grade polymers for fused-filament fabrication in the production of oral tablets. The paper also presents ways to overcome each issue. Fused-filament fabrication is a hot-melt extrusion-based 3D printing process. The paper describes the problems encountered in fused-filament fabrication with Kollidon^® VA64, which is a material that has previously been utilized in direct compression and hot-melt extrusion processes. Formulation and melt-blending strategies were employed to increase the printability of the material. The paper defines for the first time the essential parameter profile required for successful 3D printing and lists several pre-screening tools that should be employed to guide future material formulation for the fused-filament fabrication of solid dosage forms. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Hot-melt Extrusion)

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Review

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23 pages, 4361 KiB

Open AccessReview

Advanced Pharmaceutical Applications of Hot-Melt Extrusion Coupled with Fused Deposition Modelling (FDM) 3D Printing for Personalised Drug Delivery

by Deck Khong Tan, Mohammed Maniruzzaman and Ali Nokhodchi

Pharmaceutics 2018, 10(4), 203; https://doi.org/10.3390/pharmaceutics10040203 - 24 Oct 2018

Cited by 242 | Viewed by 21565

Abstract

Three-dimensional printing, also known as additive manufacturing, is a fabrication process whereby a 3D object is created layer-by-layer by depositing a feedstock material such as thermoplastic polymer. The 3D printing technology has been widely used for rapid prototyping and its interest as a [...] Read more.

Three-dimensional printing, also known as additive manufacturing, is a fabrication process whereby a 3D object is created layer-by-layer by depositing a feedstock material such as thermoplastic polymer. The 3D printing technology has been widely used for rapid prototyping and its interest as a fabrication method has grown significantly across many disciplines. The most common 3D printing technology is called the Fused Deposition Modelling (FDM) which utilises thermoplastic filaments as a starting material, then extrudes the material in sequential layers above its melting temperature to create a 3D object. These filaments can be fabricated using the Hot-Melt Extrusion (HME) technology. The advantage of using HME to manufacture polymer filaments for FDM printing is that a homogenous solid dispersion of two or more pharmaceutical excipients i.e., polymers can be made and a thermostable drug can even be introduced in the filament composition, which is otherwise impractical with any other techniques. By introducing HME techniques for 3D printing filament development can improve the bioavailability and solubility of drugs as well as sustain the drug release for a prolonged period of time. The latter is of particular interest when medical implants are considered via 3D printing. In recent years, there has been increasing interest in implementing a continuous manufacturing method on pharmaceutical products development and manufacture, in order to ensure high quality and efficacy with less batch-to-batch variations of the pharmaceutical products. The HME and FDM technology can be combined into one integrated continuous processing platform. This article reviews the working principle of Hot Melt Extrusion and Fused Deposition Modelling, and how these two technologies can be combined for the use of advanced pharmaceutical applications. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Hot-melt Extrusion)

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27 pages, 518 KiB

Open AccessReview

Hot Melt Extrusion: Highlighting Physicochemical Factors to Be Investigated While Designing and Optimizing a Hot Melt Extrusion Process

by Roberta Censi, Maria Rosa Gigliobianco, Cristina Casadidio and Piera Di Martino

Pharmaceutics 2018, 10(3), 89; https://doi.org/10.3390/pharmaceutics10030089 - 11 Jul 2018

Cited by 100 | Viewed by 9575

Abstract

Hot-melt extrusion (HME) is a well-accepted and extensively studied method for preparing numerous types of drug delivery systems and dosage forms. It offers several advantages: no solvents are required, it is easy to scale up and employ on the industrial level, and, in [...] Read more.

Hot-melt extrusion (HME) is a well-accepted and extensively studied method for preparing numerous types of drug delivery systems and dosage forms. It offers several advantages: no solvents are required, it is easy to scale up and employ on the industrial level, and, in particular, it offers the possibility of improving drug bioavailability. HME involves the mixing of a drug with one or more excipients, in general polymers and even plasticizers, which can melt, often forming a solid dispersion of the drug in the polymer. The molten mass is extruded and cooled, giving rise to a solid material with designed properties. This process, which can be realized using different kinds of special equipment, may involve modifications in the drug physicochemical properties, such as chemical, thermal and mechanical characteristics thus affecting the drug physicochemical stability and bioavailability. During process optimization, the evaluation of the drug solid state and stability is thus of paramount importance to guarantee stable drug properties for the duration of the drug product shelf life. This manuscript reviews the most important physicochemical factors that should be investigated while designing and optimizing a hot melt extrusion process, and by extension, during the different pre-formulation, formulation and process, and post-formulation phases. It offers a comprehensive evaluation of the chemical and thermal stability of extrudates, the solid physical state of extrudates, possible drug-polymer interactions, the miscibility/solubility of the drug-polymer system, the rheological properties of extrudates, the physicomechanical properties of films produced by hot melt extrusion, and drug particle dissolution from extrudates. It draws upon the last ten years of research, extending inquiry as broadly as possible. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Hot-melt Extrusion)

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19 pages, 2614 KiB

Open AccessReview

Sustained Release Drug Delivery Applications of Polyurethanes

by Michael B. Lowinger, Stephanie E. Barrett, Feng Zhang and Robert O. Williams III

Pharmaceutics 2018, 10(2), 55; https://doi.org/10.3390/pharmaceutics10020055 - 9 May 2018

Cited by 67 | Viewed by 9529

Abstract

Since their introduction over 50 years ago, polyurethanes have been applied to nearly every industry. This review describes applications of polyurethanes to the development of modified release drug delivery. Although drug delivery research leveraging polyurethanes has been ongoing for decades, there has been [...] Read more.

Since their introduction over 50 years ago, polyurethanes have been applied to nearly every industry. This review describes applications of polyurethanes to the development of modified release drug delivery. Although drug delivery research leveraging polyurethanes has been ongoing for decades, there has been renewed and substantial interest in the field in recent years. The chemistry of polyurethanes and the mechanisms of drug release from sustained release dosage forms are briefly reviewed. Studies to assess the impact of intrinsic drug properties on release from polyurethane-based formulations are considered. The impact of hydrophilic water swelling polyurethanes on drug diffusivity and release rate is discussed. The role of pore formers in modulating drug release rate is examined. Finally, the value of assessing mechanical properties of the dosage form and approaches taken in the literature are described. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Hot-melt Extrusion)

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