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Poly (lactic acid)/halloysite nanotube (PLA/HNT) nanocomposites have been studied extensively over the past few years owing to the interesting properties of the polymer, PLA, and the nanoclay, HNT, individually and as composites. In this paper, the influence of the screw speed during extrusion was investigated and was found to have a significant impact on the mechanical and thermal performance of the extruded PLA/HNT nanocomposites. To determine the effect of screw speed on PLA/HNT nanocomposites, 5 and 10 wt% of HNTs were blended into the PLA matrix through compounding at screw speeds of 40, 80, and 140 rpm. Virgin PLA was compounded for comparison. The resultant polymer melt was quench cooled onto a calendar system to produce composite films which were assessed for mechanical, thermal, chemical, and surface properties. Results illustrate that in comparison to 40 and 80 rpm, the virgin PLA when compounded at 140 rpm, indicated a significant increase in the mechanical properties. The PLA/HNT 5 wt% nanocomposite compounded at 140 rpm showed significant improvement in the dispersion of HNTs in the PLA matrix which in turn enhanced the mechanical and thermal properties. This can be attributed to the increased melt shear at higher screw speeds.

Oral tablets are a convenient form to deliver active pharmaceutical ingredients (API) and have a high level of acceptance from clinicians and patients. There is a wide range of excipients available for the fabrication of tablets thereby offering a versatile platform for the delivery of therapeutic agents to the gastrointestinal tract. However, the geometry of tablets is limited by conventional manufacturing processes. This study aimed to compare three manufacturing processes in the production of flat-faced oral tablets using the same formulation composed of a polymer blend and caffeine as a model drug: fused-filament fabrication (FFF), direct compression (DC) and injection molding (IM). Hot-melt extrusion was used to convert a powder blend into feedstock material for FFF and IM processes, while DC was performed on the powder mixture. Tablets were produced with the same dimensions and were characterized for their physical and dissolution properties. There were statistical differences in the physical properties and drug release profiles of the tablets produced by the different manufacturing processes. DC tablets displayed immediate release, IM provided sustained release over 48 h, and FFF tablets displayed both release types depending on the printing parameters. FFF continues to demonstrate high potential as a manufacturing process for the efficient production of personalized oral tablets.

Calcium carbonate (CaCO3) is frequently added to polyethylene (PE) as a filler to reduce costs. An alternative to CaCO3, calcium fluoride (CaF2) was proposed in this research. PE/CaCO3 and PE/CaF2 composites in a wide composition range (0–60 wt.%) were prepared through a parallel twin screw extruder. Results indicated better interaction of CaF2 with PE matrix which improved samples yield stress. Statistical analysis showed the filler type was more influential factor on the yield stress while filler loading was not a statistically significant one. In contrast, crystallinity was strongly depended on the filler loading. The dynamic mechanical and rheological investigations revealed that PE/CaF2 composites had higher stiffness at ambient temperature and possessed lower viscosity below 40 wt.% of filler loading compared to PE/CaCO3 which could reduce the processing cost. Therefore, regarding its low price and good functional properties, CaF2 can be a promising alternative to CaCO3.

Poly (ether ether ketone) (PEEK) is a high-performance engineering thermoplastic polymer with potential for use in a variety of metal replacement applications due to its high strength to weight ratio. This combination of properties makes it an ideal material for use in the production of bespoke replacement parts for out-of-earth manufacturing purposes, in particular on the International Space Station (ISS). Additive manufacturing (AM) may be employed for the production of these parts, as it has enabled new fabrication pathways for articles with complex design considerations. However, AM of PEEK via fused filament fabrication (FFF) encounters significant challenges, mostly stemming from the semi crystalline nature of PEEK and its associated high melting temperature. This makes PEEK highly susceptible to changes in processing conditions which leads to a large reported variation in the literature on the final performance of PEEK. This has limited the adaption of FFF printing of PEEK in space applications where quality assurance and reproducibility are paramount. In recent years, several research studies have examined the effect of printing parameters on the performance of the 3D-printed PEEK parts. The aim of the current review is to provide comprehensive information in relation to the process-structure-property relationships in FFF 3D-printing of PEEK to provide a clear baseline to the research community and assesses its potential for space applications, including out-of-earth manufacturing.

Catalytic graphitization of biocarbon prepared from Miscanthus grass was possible through chemical treatment with iron(III) nitrate, Fe(NO3)3, and cobalt(II) nitrate, Co(NO3)2. The pyrolysis monitoring, until the temperature of 900 °C, permitted for the primary analysis of the effects of the generated catalysis species on biomass degradation. Then both Raman spectroscopy and X-ray diffraction (XRD) allowed for the observation of microstructural changes between the samples treated with metal catalysts and the untreated samples. The samples treated with both iron and cobalt nitrates are twice as efficient at forming ordered graphite than the treated sample with the catalysts used separately. This may be due to FeCo nanoparticles generated in situ during pyrolysis. These results show that the morphology and allotropy of renewable biocarbon can be tailored in such a way that it can be applied to design smart materials.

The new frontier of medicine is the personalization of treatment to match a patient’s individual needs. Fused-filament fabrication (FFF) offers a platform for the personalization of drug dosage forms, but one of its chief shortcomings compared to other tablet production methods such as dry compression and wet granulation is relatively low throughput. Conversely, injection molding (IM) is a manufacturing technique for the high-volume production of parts, but in which individual part customization is both expensive and slow requiring the modification of expensive mold tooling. Mass-customization is the manufacture of custom products that match the needs of individual consumers but which are produced at the low unit cost associated with high-volume production. We successfully integrated for the first time FFF with IM in a multi-step manufacturing process for the production of custom bilayer tablets loaded with two active pharmaceutical ingredients used in the treatment of cardiovascular disease. The FFF layer was loaded with the diuretic hydrochlorothiazide, while the IM layer was loaded with lovastatin. Infill percentage was varied for the FFF layer as a means to modify drug release. The IM injection pressure was evaluated for its effect on drug release and layer-layer adhesion. The bilayer tablets obtained offered different combinations of drug release profiles, which were governed by a combination of factors, including surface area to volume ratio; IM injection volume penetration into the FFF layer; FFF infill percentage; layer tortuosity and porosity. These different parameters could be utilized to modify the individual release of both drugs from the bilayer tablet. Thus for the first time, we have demonstrated a viable method for the mass-customization of oral tablets which could hasten the rollout of personalized medicine. yes

Biodegradable polymers play a crucial role in the medical device field, with a broad range of applications such as suturing, drug delivery, tissue engineering, scaffolding, orthopaedics, and fixation devices. Poly-l-lactic acid (PLLA) is one of the most commonly used and investigated biodegradable polymers. The objective of this study was to determine the influence low shear microbore extrusion exerts on the properties of high molecular weight PLLA for medical tubing applications. Results showed that even at low shear rates there was a considerable reduction in molecular weight (Mn = 7&ndash, 18%) during processing, with a further loss (Mn 11%) associated with resin drying. An increase in melt residence time from ~4 mins to ~6 mins, translated into a 12% greater reduction in molecular weight. The degradation mechanism was determined to be thermal and resulted in a ~22-fold increase in residual monomer. The differences in molecular weight between both batches had no effect on the materials thermal or morphological properties. However, it did affect its mechanical properties, with a significant impact on tensile strength and modulus. Interestingly there was no effect on the elongational proprieties of the tubing. There was also an observed temperature-dependence of mechanical properties below the glass transition temperature.

Additive manufacturing has been of great interest of research in various applications due to their ease in processability, cost effectiveness and adaptability. In this study Poly Lactic Acid (PLA) was used as the base polymer which was reinforced with Halloysite Nanotubes (HNT) powder as they are known to be biodegradable and has high mechanical properties individually. HNT loadings with 3% and 5% were added to PLA by the method of twin screw extrusion and pelletized. For comparison, the PLA on its own was also extruded and pelletized. The resultant homogeneous pellets was extruded successfully into filaments of 1.75±0.10 mm diameter using twin screw extruder with specialized die fixed to the extruder for the manufacture of production grade 3D printing filament. This resultant filament was utilized for Fused Filament Fabrication (FFF) into standard tensile test bars and 25mm medical implants using a standard FFF printing machine. The 3D printed samples were characterized for mechanical properties by uniaxial tensile test and thermal stability by Differential scanning calorimetry. Interestingly there was no significant change in the mechanical properties of the 3D printed tensile bars due to the processing parameters during FFF. However, the decrease in cold crystallization temperature by DSC indicates the nucleating effect of the HNT on the PLA matrix which in turn increases the mechanical properties. We could successfully 3D print model medical implants.

Calcium carbonate (CaCO3) is often treated with stearic acid (SA) to decrease its polarity. However, the method of application of the SA treatments has a strong influence on CaCO3 thermoplastic composite’s interfacial structure and distribution. Several of papers describe the promising effects of SA surface treatment, but few compare the treatment process and its effect on the properties of the final thermoplastic composite. In the current study, we assessed a new SA treatment method, namely, complex treatment for polymer composite fabrication with HDPE. Subsequently, a comparative study was performed between the “complex” process and the other existing methods. The composites were assessed using different experiments included scanning electron microscopy (SEM), void content, density, wettability, differential scanning calorimetry (DSC), and tensile tests. It was observed that the “complex” surface treatment yielded composites with a significantly lower voids content and higher density compared to other surface treatments. This indicates that after the “complex” treatment process, the CaCO3 particles and HDPE matrix are more tightly packed than other methods. DSC and wettability results suggest that the “wet” and “complex” treated CaCO3 composites had a significantly higher heat of fusion and moisture resistance compared to the “dry” treated CaCO3 composites. Furthermore, “wet” and “complex” treated CaCO3 composites have a significantly higher tensile strength than the composites containing untreated and “dry” treated CaCO3. This is mainly because the “wet” and “complex” treatment processes have increased adsorption density of stearate, which enhances the interfacial interaction between matrix and filler. These results confirm that the chemical adsorption of the surfactant ions at the solid-liquid interface is higher than at other interface. From this study, it was concluded that the utilization of the “complex” method minimised the negative effects of void coalescence provides key information for the improvement of existing processes.

Multipurpose prevention technologies (MPTs) are preferably single dosage forms designed to simultaneously address multiple sexual and reproductive health needs, such as unintended pregnancy, HIV infection and other sexually transmitted infections (STIs). This manuscript describes the development of a range of multilayered vaginal tablets, with both immediate and sustained release layers capable of delivering the antiretroviral drug dapivirine, the contraceptive hormone levonorgestrel, and the anti-herpes simplex virus drug acyclovir at independent release rates from a single dosage form. Depending on the design of the tablet in relation to the type (immediate or sustained release) or number of layers, the dose of each drug could be individually controlled. For example one tablet design was able to provide immediate release of all three drugs, while another tablet design was able to provide immediate release of both acyclovir and levonorgestrel, while providing sustained release of Dapivirnie for up to 8 hours. A third tablet design was able to provide immediate release of both acyclovir and levonorgestrel, a large initial burst of Dapivirine, followed by sustained release of Dapivirine for up to 8 hours. All of the tablets passed the test for friability with a percent friability of less than 1%. The hardness of all tablet designs were between 115 and 153 Newtons, while their drug content met the European Pharmacopeia 2.9.40 Uniformity of Dosage units acceptance value at level 1 and 2. Finally, the accelerated stability of all three actives was significantly enhanced in comparison to a mixed drug control. yes

A new type of polymer composite was synthesized from peat ash which was obtained as industrial waste. This was added to high density polyethylene (HDPE) at varying mixing ratios and the resulting products were characterized using different experiments which included Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), melt flow index (MFI), density, wettability, tensile test, flexural test and cost analysis. The effects of various ash loadings and the use of the maleic anhydride grafted high density polyethylene (HDPE-g-MA) compatibilizer on the physical and mechanical properties of composites were investigated. It was observed that the utilization of peat ash significantly increased the tensile strength and the flexural modulus, where also reducing raw material cost. Incorporating (HDPE-g-MA) in the composites formulation led to further increases in tensile and flexural properties. Conversely, there was a significant decrease of impact strength found for all composites in comparison to the virgin HDPE. And the impact strengths generally decreased as peat ash content increases. Microstructural analyses showed that surface treated peat ash particles appeared to be well-incorporated into the HDPE matrix, as intimated polymer/peat ash contact was observed. In addition, the melt flow index of the composites decreased remarkably with an increase in peat ash content. No significant water uptake effect was detected on peat ash composites indicating that these materials could be used as a direct replacement for HDPE in applications where impact strength is not a critical factor. Furthermore, the use of peat ash increased the composite density in comparison to virgin HDPE. Nevertheless, as peat ash reinforcement does offer increased tensile and flexural properties, this may make the end product lighter as lower wall thickness parts can be used to fulfil the same function. From this study, it was concluded that the utilization of the peat ash from peat fired power stations has proved to have significant value-added potential as a filler material in polymer composites.

Stereolithography (SLA)-based 3D printing has proven to have several advantages over traditional fabrication techniques as it allows for the control of hydrogel synthesis at a very high resolution, making possible the creation of tissue-engineered devices with microarchitecture similar to the tissues they are replacing. Much of the previous work in hydrogels for tissue engineering applications have utilised the ultraviolet (UV) chamber bulk photopolymerisation method for preparing test specimens. Therefore, it is essential to directly compare SLA 3D printing to this more traditional approach to elucidate the differences in hydrogels prepared by each fabrication method. Polyethyleneglycol dimethacrylate (PEGDMA) is an ideally suited material for a comparative study of the impact that SLA fabrication has on performance, as the properties of traditional UV chamber-cured hydrogels have been extensively characterised. The present study was conducted to compare the material properties of PEGDMA hydrogels prepared using UV chamber photopolymerisation and SLA 3D printing. From the subsequent testing, SLA-fabricated hydrogels were shown to maintain similar thermal and chemical performance to UV chamber-cured hydrogels but had a higher compressive strength and tensile stiffness, as well as increased hydrophilicity. These differences are attributed to the increased exposure to UV light SLA samples received compared to traditionally UV chamber-cured samples.

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. yes

Carbon fibre reinforced polymer composites offer significant improvement in overall material strength to weight, when compared with metals traditionally used in engineering. As a result, they are replacing metals where overall weight is a significant consideration, such as in the aerospace and automotive industries. However, due to their laminate structure, delamination is a prime concern. Through-thickness stitching has been shown to be a relatively simple method of improving resistance to delamination. In this paper, monofilament and multifilament fibres of a similar overall diameter were characterised and their properties compared for their suitability as stitching yarns. Dissimilar to other published works which rely on commercially available materials, such as polyparaphenylene terephthalamide, criteria were produced on the required properties and two potentially promising polymers were selected for extrusion. It was found that although the multifilament fibres had a greater ultimate tensile strength, they began to yield at a lower force than their monofilament equivalent. yes

Nanocomposite-based drug delivery systems with intrinsic controlled release properties are of great interest in biomedical applications. We report a novel polylactic acid (PLA)/halloysite nanotube (HNT) nanocomposite-based drug delivery system. PLA/HNT nanocomposites have shown immense potential for use in biomedical applications due to their favorable cyto- and hemo-compatibility. The objective of this study was to evaluate the release of active pharmaceutical ingredients (API) from PLA/HNT composites matrix and the effect of preloading the API into the lumen of the HNT on its release profile. Aspirin was used in this study as a model drug as it is a common nonsteroidal anti-inflammatory and antiplatelet agent widely used for various medical conditions. These two types of drug-loaded PLA/HNT nanocomposites were characterised by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), surface wettability and mechanical testing. Statistical analysis was conducted on numerical data. Drug entrapment and in vitro drug release studies were conducted using UV spectrophotometry. Results indicate that aspirin was successfully loaded into the lumen of HNT, which resulted in the sustained release of aspirin from the nanocomposites. Furthermore, the addition of HNT into the polymer matrix increased the mechanical properties, indicating its suitability as a drug-eluting reinforcing agent.

A matrix-type silicone elastomer vaginal ring providing 28-day continuous release of dapivirine (DPV) ⿿ a lead candidate human immunodeficiency virus type 1 (HIV-1) microbicide compound ⿿ has recently demonstrated moderate levels of protection in two Phase III clinical studies. Here, next-generation matrix and reservoir-type silicone elastomer vaginal rings are reported for the first time offering simultaneous and continuous in vitro release of DPV and the contraceptive progestin levonorgestrel (LNG) over a period of between 60 and 180 days. For matrix-type vaginal rings comprising initial drug loadings of 100, 150 or 200 mg DPV and 0, 16 or 32 mg LNG, Day 1 daily DPV release values were between 4132 and 6113 μg while Day 60 values ranged from 284 to 454 μg. Daily LNG release ranged from 129 to 684 μg on Day 1 and 2⿿91 μg on Day 60. Core-type rings comprising one or two drug-loaded cores provided extended duration of in vitro release out to 180 days, and maintained daily drug release rates within much narrower windows (either 75⿿131 μg/day or 37⿿66 μg/day for DPV, and either 96⿿150 μg/day or 37⿿57 μg/day for LNG, depending on core ring configuration and ignoring initial lag release effect for LNG) compared with matrix-type rings. The data support the continued development of these devices as multi-purpose prevention technologies (MPTs) for HIV prevention and long-acting contraception. yes

Non-degradable polymers have an important function in medicine. Solid dosage forms for longer term implantation require to be constructed from materials that will not degrade or erode over time and also offer the utmost biocompatibility and biostability. This review details the three most important non-degradable polymers for the production of solid dosage forms - silicone elastomer, ethylene vinyl acetate and thermoplastic polyurethane. The hydrophobic, thermoset silicone elastomer is utilised in the production of a broad range of devices, from urinary catheter tubing for the prevention of biofilm to intravaginal rings used to prevent HIV transmission. Ethylene vinyl acetate, a hydrophobic thermoplastic, is the material of choice of two of the world's leading forms of contraception - Nuvaring® and Implanon®. Thermoplastic polyurethane has such a diverse range of building blocks that this one polymer can be hydrophilic or hydrophobic. Yet, in spite of this versatility, it is only now finding utility in commercialised drug delivery systems. Separately then one polymer has a unique ability that differentiates it from the others and can be applied in a specific drug delivery application; but collectively these polymers provide a rich palette of material and drug delivery options to empower formulation scientists in meeting even the most demanding of unmet clinical needs. Therefore, these polymers have had a long history in controlled release, from the very beginning even, and it is pertinent that this review examines briefly this history while also detailing the state-of-the-art academic studies and inventions exploiting these materials. The paper also outlines the different production methods required to manufacture these solid dosage forms as many of the processes are uncommon to the wider pharmaceutical industry. yes