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The creation of products with personalized or innovative features in the pharmaceutical sector by using innovative technologies such as three-dimensional (3D) printing is particularly noteworthy, especially in the realm of compounding pharmacies. In this work, 3D printed capsule devices (CDs) with different wall thicknesses (0.2, 0.3, 0.4, 0.6, and 0.9 mm) and sizes were designed and successfully fabricated varying printing parameters such as extrusion temperature, printing speed, material flow percent, and nozzle diameter. The physicochemical, pharmaceutical, and biopharmaceutical performance of these CDs was evaluated with the aim of achieving an immediate drug release profile comparable to hard gelatin capsules (HGC) for use in magistral compounding. It was observed that the disintegration time of the CDs increased with wall thickness, which correlated with a slower drug release rate. CDs with configurations presenting 0.4 mm wall thickness and sizes comparable to HGC n° 0, 1, and 2 demonstrated satisfactory weight uniformity, short disintegration times, and immediate drug release, indicating their potential as effective devices in future compounding pharmacy applications. In addition, a modified Weibull-type model was proposed that incorporates wall thickness as a new variable in predicting dissolution profiles. This model improves the process of selecting a specific wall thickness to achieve the desired dissolution rate within a specified time frame.
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Prototyping analytical devices with three-dimensional (3D) printing techniques is becoming common in research laboratories. The attractiveness is associated with printers' price reduction and the possibility of creating customized objects that could form complete analytical systems. Even though 3D printing enables the rapid fabrication of electrochemical sensors, its wider adoption by research laboratories is hindered by the lack of reference material and the high "entry barrier" to the field, manifested by the need to learn how to use 3D design software and operate the printers. This review article provides insights into fused deposition modeling 3D printing, discussing key challenges in producing electrochemical sensors using currently available extrusion tools, which include desktop 3D printers and 3D printing pens. Further, we discuss the electrode processing steps, including designing, printing conditions, and post-treatment steps. Finally, this work shed some light on the current applications of such electrochemical devices that can be a reference material for new research involving 3D printing.
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The global healthcare crisis with the COVID-19 pandemic has placed a significant overwhelming demand for intubation procedures and the need for reliable and accessible video laryngoscopes. The purpose of this scoping and technological review is to provide a comprehensive overview of the current state of the art, covering the period from 2007 to 2022, pertaining to the manufacturing process, characteristics, and validation of video laryngoscopes produced using additive manufacturing techniques. Following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), an exhaustive search was conducted across nine prominent databases (PubMed, Web of Science, Scopus, Cochrane, Prospero, Scielo, Embase, Lilacs, Virtual Health Libraries-VHL) and four patent databases (EPO/ESPACENET, WIPO/PATENTSCOPE, National Institute of Industrial Property (INPI), Google Patents). The main materials utilized for the impression, as well as the physical characteristics of the device are introduced at first. Crucial aspects to facilitate proper visualization of the anatomical structures during endotracheal intubation as the optimal angulation of the blade, the mechanical resistance of the device, traction force on the jaw, intubation time, and the experimental methods employed to validate its performance were reviewed in terms of their recent advances.
Subject(s)
Laryngoscopes , Humans , Pandemics , Intubation, Intratracheal/methods , Video RecordingABSTRACT
Three-dimensional printing technologies can be implemented for the fabrication of personalized vaginal rings (VRs) as an alternative approach to traditional manufacturing. Although several studies have demonstrated the potential of additive manufacturing, there is a lack of knowledge concerning the opinions of patients and clinicians. This study aimed to investigate the perception of women and gynecologists regarding VRs with personalized shapes. The devices were printed with different designs (traditional, "Y", "M", and flat circle) by Fused Deposition Modeling for a cross-sectional survey with 155 participants. Their anticipated opinion was assessed through a questionnaire after a visual/tactile analysis of the VRs. The findings revealed that most women would feel comfortable using some of the 3D-printed VR designs and demonstrated good acceptability for the traditional and two innovative designs. However, women presented multiple preferences when the actual geometry was assessed, which directly related to their age, previous use of the vaginal route, and perception of comfort. In turn, gynecologists favored prescribing traditional and flat circle designs. Overall, although there was a difference in the perception between women and gynecologists, they had a positive opinion of the 3D-printed VRs. Finally, the personalized VRs could lead to an increase in therapeutic adherence, by meeting women's preferences.
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INTRODUCTION: Although the administration of drugs on the skin is a safe and noninvasive therapeutic alternative, producing formulations capable of disrupting the cutaneous barriers is still a challenge. In this scenario, extrusion-based techniques have emerged as disruptive technologies to ensure unique drug-excipient interactions that facilitate drug skin diffusion for systemic or local effect and even mean the key to obtain viable industrial products. AREAS COVERED: This article presents a comprehensive overview of extrusion-based techniques in developing pharmaceutical dosage forms for topical or transdermal drug delivery. First, the theoretical basis of how extrusion-based techniques can optimize the permeation of drugs through the skin is examined. Then, the current state-of-the-art of drug products developed by extrusion-based techniques, specifically by hot-melt extrusion (HME) and fused deposition modeling (FDM) 3D printing, are discussed and contrasted with the current pharmaceutical processes. EXPERT OPINION: A wide variety of pharmaceutical products can be obtained using HME and FDM 3D printing, including new dosage forms designed for a perfect anatomical fit. Despite the limitations of pharmaceutical products produced with HME and FDM 3D printing regarding thermal stability and available excipients, the advantages in industrial adaptability and improved bioavailability allied with patient-match devices certainly deserve full attention and investment.
Subject(s)
Hot Melt Extrusion Technology , Technology, Pharmaceutical , Humans , Technology, Pharmaceutical/methods , Pharmaceutical Preparations , Drug Compounding/methods , Administration, Cutaneous , Excipients , Drug Liberation , Drug Delivery Systems/methods , TabletsABSTRACT
The in-situ formation of nanoparticles from polymer-based solid medicines, although previously described, has been overlooked despite its potential to interfere with oral drug bioavailability. Such polymeric pharmaceuticals are becoming increasingly common on the market and can become even more popular due to the dizzying advance of 3D printing medicines. Hence, this work aimed to study this phenomenon during the dissolution of 3D printed tablets produced with three different polymers, hydroxypropylmethylcellulose acetate succinate (HPMCAS), polyvinyl alcohol (PVA), and Eudragit RL PO® (EUD RL) combined with plasticizers and the model drug naringenin (NAR). The components' interaction, dissolution behavior, and characteristics of the formed particles were investigated employing thermal, spectroscopic, mechanical, and chromatographic assays. All the systems generated stable spherical-shaped particles throughout 24 h, encapsulating over 25% of NAR. Results suggest encapsulation efficiencies variations may depend on interactions between polymer-drug, drug-plasticizer, and polymer-plasticizer, which formed stable nanoparticles even in the drug absence, as observed with the HPMCAS and EUD RL formulations. Additionally, components solubility in the medium and previous formulation treatments are also a decisive factor for nanoparticle formation. In particular, the treatment provided by hot-melt extrusion and FDM 3D printing affected the dissolution efficiency enhancing the interaction between the components, reverberating on particle size and particle formation kinetics mainly for HPMCAS and EUD RL. In conclusion, the 3D printing process influences the in-situ formation of nanoparticles, which can directly affect oral drug bioavailability and needs to be monitored.
Subject(s)
Plasticizers , Polymers , Drug Liberation , Polymers/chemistry , Solubility , Tablets/chemistry , Printing, Three-Dimensional , Technology, Pharmaceutical/methodsABSTRACT
Fused deposition modeling (FDM) 3D printing is a promising additive manufacturing technique to produce low-cost disposable electrochemical devices. However, the print of devices like well-known screen-printed electrodes (all electrodes on the same device) is difficult using the available technology (few materials available for production of working electrodes). In this paper we present a procedure to produce disposable and robust electrochemical devices by FDM 3D printing that allows reproducible analysis of small volumes (50-2000 µL). The device consists of just two printed parts that allow easy coupling of different conductive materials for using as disposable or non-disposable working electrodes with reproducible geometric area. Printed counter and pseudo-reference electrodes can also be easily fitted into the microcell. Moreover, conventional counter (platinum wire) and mini reference electrodes can also be used. As a proof of concept, paracetamol, cocaine and uric acid were used as model analytes using different materials as working electrodes. Linear calibration curves (r > 0.99) with similar slopes (0.29 ± 0.01 µA µmol L-1; RSD = 3.4%) were obtained by square wave voltammetry (SWV) using a complete printed system and different volumes of standard solutions of paracetamol (50, 100, and 200 µL). For uric acid, a linear range of 10-125 µmol L-1 (r > 0.99), was obtained using differential pulse voltammetry as the electrochemical technique and a disposable laser-induced graphene base as the working electrode. With the coupling of boron-doped diamond working electrode, screening tests were successfully performed in seized cocaine samples with selective detection of cocaine in the presence of its most common adulterants. The production cost per unit of a complete electrochemical system is around US 5.00. In large-scale production, only the working electrode needs to be replaced while the microcell and counter/pseudo reference electrodes do not need to be discarded.
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In the context of the preservation of natural resources, researchers show a growing interest in developing eco-friendly materials based on recycled polymers and natural fiber biocomposites to minimize plastic and agroindustrial waste pollution. The development of new materials must be integrated within the circular economy concepts to guarantee sustainable production. In parallel, fused deposition modeling, an additive manufacturing technology, provides the opportunity to use these new materials in an efficient and sustainable manner. This review presents the context of plastics and agro-industrial fiber pollution, followed by the opportunity to give them added value by applying circular economy concepts and implementing these residues to develop new materials for the manufacture of fused deposition modeling 3D printing technique feedstock. Colombian perspective is highlighted since 3D printing technology is growing there, and Colombian biodiversity represents a high reservoir of materials. Also, recycling in Colombia promotes compliance with the 2030 Agenda and the Sustainable Development Goals.
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The use of 3D printing for the production of systems intended for oral delivery of diet supplements in the veterinary pharmacy constitutes an attractive technology that has remained unexplored. In this sense, this work studies the design and 3D printing of capsular devices that allow the modified release of urea, which is frequently used as a source of non-protein nitrogen in ruminants, but highly toxic if fast ingested. The devices were printed with combinations of polylactic acid (PLA, water-insoluble) and polyvinyl alcohol (PVA, water-soluble) in order to modulate the urea release through the different parts. The optimization of the designs as well as printing parameters such as extrusion temperature, printing speed, retraction distance and nozzle speed resulted critical to obtain successful capsular devices. In addition, the dissolution studies confirmed that the developed designs showed a controlled release of urea, especially the ones that presented internal partitions. Finally, Logistic and Weibull equations were the kinetic models that best fitted the experimental data corresponding to functions that describe S-shaped dissolution profiles. Overall, this work constitutes a proof of concept and provides the first steps in the development of 3D printed simple devices for the controlled release of supplements and drugs in veterinary pharmacy.
Subject(s)
Printing, Three-Dimensional , Urea , Animals , Tablets , Drug Liberation , Delayed-Action Preparations , Capsules , Water , Ruminants , Technology, Pharmaceutical/methodsABSTRACT
The 3D printing is described of a complete and portable system comprising a batch injection analysis (BIA) cell and an electrochemical platform with eight sensing electrodes. Both BIA and electrochemical cells were printed within 3.4 h using a multimaterial printer equipped with insulating, flexible, and conductive filaments at cost of ca. ~ U$ 1.2 per unit, and their integration was based on a threadable assembling without commercial component requirements. Printed electrodes were exposed to electrochemical/Fenton pre-treatments to improve the sensitivity. Scanning electron microscopy and electrochemical impedance spectroscopy measurements upon printed materials revealed high-fidelity 3D features (90 to 98%) and fast heterogeneous rate constants ((1.5 ± 0.1) × 10-3 cm s-1). Operational parameters of BIA cell were optimized using a redox probe composed of [Fe(CN)6]4-/3- under stirring and the best analytical performance was achieved using a dispensing rate of 9.0 µL s-1 and an injection volume of 2.0 µL. The proof of concept of the printed device for bioanalytical applications was evaluated using adrenaline (ADR) as target analyte and its redox activities were carefully evaluated through different voltammetric techniques upon multiple 3D-printed electrodes. The coupling of BIA system with amperometric detection ensured fast responses with well-defined peak width related to the oxidation of ADR applying a potential of 0.4 V vs Ag. The fully 3D-printed system provided suitable analytical performance in terms of repeatability and reproducibility (RSD ≤ 6%), linear concentration range (5 to 40 µmol L-1; R2 = 0.99), limit of detection (0.61 µmol L-1), and high analytical frequency (494 ± 13 h-1). Lastly, artificial urine samples were spiked with ADR solutions at three different concentration levels and the obtained recovery values ranged from 87 to 118%, thus demonstrating potentiality for biological fluid analysis. Based on the analytical performance, the complete device fully printed through additive manufacturing technology emerges as powerful, inexpensive, and portable tool for electroanalytical applications involving biologically relevant compounds.
Subject(s)
Dielectric Spectroscopy , Soot , Electrodes , Printing, Three-Dimensional , Reproducibility of ResultsABSTRACT
This review summarizes the most recent advances from technological and physico-chemical perspectives to improve several remaining issues in polymeric materials' additive manufacturing (AM). Without a doubt, AM is experimenting with significant progress due to technological innovations that are currently advancing. In this context, the state-of-the-art considers both research areas as working separately and contributing to developing the different AM technologies. First, AM techniques' advantages and current limitations are analyzed and discussed. A detailed overview of the efforts made to improve the two most extensively employed techniques, i.e., material extrusion and VAT-photopolymerization, is presented. Aspects such as the part size, the possibility of producing parts in a continuous process, the improvement of the fabrication time, the reduction of the use of supports, and the fabrication of components using more than one material are analyzed. The last part of this review complements these technological advances with a general overview of the innovations made from a material perspective. The use of reinforced polymers, the preparation of adapted high-temperature materials, or even the fabrication of metallic and ceramic parts using polymers as supports are considered. Finally, the use of smart materials that enable the fabrication of shape-changing 3D objects and sustainable materials will also be explored.
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PURPOSE: This in vitro study evaluated the dimensional accuracy of three 3D printers and one milling machine with their respective polymeric materials using a simplified geometrical model. MATERIALS AND METHODS: A simplified computer-aided design (CAD) model was created. The test samples were fabricated with three 3D printers: a dental desktop stereolithography (SLA) printer, an industrial SLA printer, and an industrial fused deposition modeling (FDM) printer, as well as a 5-axis milling machine. One polymer material was used per industrial printer and milling machine while two materials were used with the dental printer for a total of five study groups. Test specimens were then digitized using a laboratory scanner. The virtual outer caliper method was used to measure the linear dimensions of the digitized 3D printed and milled specimens in x-, y-, and z-axes, and compare them to the known values of the CAD model. Data were analyzed with Kruskal-Wallis one-way ANOVA on Ranks followed by the Tukey's test. RESULTS: Milled specimens were not significantly different from the CAD model in any dimension (p > 0.05). All 3D printed specimens were significantly different from the CAD model in all dimensions (p = 0.01), except the dental SLA 3D printer with one of the polymers tested (Bis-GMA) which was not significantly different in two (x and z) dimensions (p = 0.4 and p = 0.12). CONCLUSIONS: The milling technology tested provided greater dimensional accuracy than the selected 3D printing. Printer, printing technology, and material selection affected the accuracy of the printed model.
Subject(s)
Computer-Aided Design , Stereolithography , Polymers , Printing, Three-DimensionalABSTRACT
In the current study, we have coupled Fused Deposition Modelling (FDM) for the fabrication of plain polyvinyl alcohol (PVA) tablets followed by dispensing of minoxidil ethanolic solutions using inkjet printing. The use of a drop-on-solid printing approach facilitates an accurate and reproducible process while it controls the deposition of the drug amounts. For the purpose of the study, the effect of the solvent was investigated and minoxidil ink solutions of ethanol 70% v/v (P70) or absolute ethanol (P100) were applied on the plain PVA tablets. Physicochemical characterization showed that solvent miscibility with the polymer substrate plays a key role and can lead to the formation of drug crystals on the surface or drug absorption in the polymer matrix. The produced minoxidil tablets showed sustained release profiles or initial bursts strongly affected by the solvent grade used for dispensing the required dose on drug loaded 3D printed tablets. This paradigm demonstrates that the coupling of FDM and inkjet printing technologies could be used for rapid development of personalized dosage forms.
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Fused deposition modeling (FDM) uses lattice arrangements, known as infill, within the fabricated part. The mechanical properties of parts fabricated via FDM are dependent on these infill patterns, which make their study of great relevance. One of the advantages of FDM is the wide range of materials that can be employed using this technology. Among these, polylactic acid (PLA)-wood has been recently gaining attention as it has become commercially available. In this work, the stiffness of two different lattice structures fabricated from PLA-wood material using FDM are studied: hexagonal and star. Rectangular samples with four different infill densities made of PLA-wood material were fabricated via FDM. Samples were subjected to 3-point bending to characterize the effective stiffness and their sensitivity to shear deformation. Lattice beams proved to be more sensitive to shear deformations, as including the contribution of shear in the apparent stiffness of these arrangements leads to more accurate results. This was evaluated by comparing the effective Young's modulus characterized from 3-point bending using equations with and without shear inclusion. A longer separation between supports yielded closer results between both models (~41% for the longest separation tested). The effective stiffness as a function of the infill density of both topologies showed similar trends. However, the maximum difference obtained at low densities was the hexagonal topology that was ~60% stiffer, while the lowest difference was obtained at higher densities (star topology being stiffer by ~20%). Results for stiffness of PLA-wood samples were scattered. This was attributed to the defects at the lattice element level inherent to the material employed in this study, confirmed via micro-characterization.
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In order to provide a second economic life to agave fibers, an important waste material from the production of tequila, filaments based on polylactic acid (PLA) were filled with agave fibers (0, 3, 5, 10 wt%), and further utilized to produce biocomposites by fused deposition modeling (FDM)-based 3D printing at two raster angles (-45°/45° and 0°/90°). Differential scanning calorimetry, water uptake, density variation, morphology, and composting of the biocomposites were studied. The mechanical properties of the biocomposites (tensile, flexural, and Charpy impact properties) were determined following ASTM international norms. The addition of agave fibers to the filaments increased the crystallinity value from 23.7 to 44.1%. However, the fibers generated porous structures with a higher content of open cells and lower apparent densities than neat PLA pieces. The printing angle had a low significant effect on flexural and tensile properties, but directly affected the morphology of the printed biocomposites, positively influenced the impact strength, and slightly improved the absorption values for biocomposites printed at -45°/45°. Overall, increasing the concentrations of agave fibers had a detrimental effect on the mechanical properties of the biocomposites. The disintegration of the biocomposites under simulated composting conditions was slowed 1.6-fold with the addition of agave fibers, compared to neat PLA.
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3D printing is a hot topic in electroanalytical chemistry, allowing the construction of custom cells and sensors at affordable prices. In this work, we describe a novel small and practical 3D-printed electrochemical cell. The cell's body, manufactured in ABS on a 3D printer, is composed by three parts easily screwed: solution vessel, stick and cover with two embedded 3D-pen-printed carbon black-polylactic acid (CB-PLA) electrodes (counter and pseudo-reference). The cell is compatible with any planar working electrode, in which boron-doped diamond, graphite sheet (GS) and 3D-printed CB-PLA were shown as examples. A new alternative protocol to quickly produce 3D-printed sensors using a 3D pen and other low-cost apparatus is also proposed. The voltammetric performance of each evaluated sensor was carried out in the presence of redox probe ferricyanide and paracetamol as model analyte, and the surfaces were characterized by electrochemical impedance spectroscopy and scanning electrochemical microscopy. To present an analytical application of the 3D-printed cell, low-cost flexible sensors (GS and CB-PLA) were used as integrated platforms for sampling and detection of solid drugs. As a proof-of-concept, traces of drugs with a historic of counterfeit or adulteration (sildenafil citrate, tadalafil, losartan and 17α-ethinylestradiol) were abrasively sampled over the sensor and assembled on 3D-printed cell to perform a fast voltammetric scan in the presence of only 500 µL of electrolyte. This protocol is attractive for pharmaceutical and forensic sciences as a simple preliminary screening method which could identify the presence or absence of the suspicious drug as well as impurities or adulterants. The 3D-printed cell was also used for the determination of 17α-ethinylestradiol in a contraceptive pill to demonstrate a quantitative analysis. The cell is quickly printed (90 min), cheap (US$ 0.30) and requires low electrolyte volumes (0.5-3.0 mL), being suitable to be used in several other electroanalyses, especially for on-site applications.
Subject(s)
Graphite , Drug Evaluation, Preclinical , Electrodes , Oxidation-Reduction , Printing, Three-DimensionalABSTRACT
Fused deposition modeling represents a flexible and relatively inexpensive alternative for the production of custom-made polymer lattices. However, its limited accuracy and resolution lead to geometric irregularities and poor mechanical properties when compared with the digital design. Although the link between geometric features and mechanical properties of lattices has been studied extensively, the role of manufacturing parameters has received little attention. Additionally, as the size of cells/struts nears the accuracy limit of the manufacturing process, the interaction between geometry and manufacturing parameters could be decisive. Hence, the influence of three geometric and two manufacturing parameters on the mechanical behavior was evaluated using a fractional factorial design of experiments. The compressive behavior of two miniature lattice structures, the truncated octahedron and cubic diamond, was evaluated, and multilinear regression models for the elastic modulus and plateau stress were developed. Cell size, unit cell type, and strut diameter had the largest impact on the mechanical properties, while the influence of feedstock material and layer thickness was very limited. Models based on factorial design, although limited in scope, could be an effective tool for the design of customized lattice structures.
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Dental prosthesis and restoration technologies have been developed in the past years. Despite the advantages of additive manufacturing, computer-aided design, and computer-aided manufacturing technologies are still the dominant type of method for fabricating prostheses. Therefore, the main goal of this study is to assess the feasibility of using indirect fused deposition modeling to fabricate dental prosthesis made of ZrSiO4-glass composites. To achieve this goal, filaments were filled by 90% of ZrSiO4 and 50 µm glass spheres to fabricate prosthesis. Multivariable approach was applied to evaluate the feasibility of the proposed method. Holding temperature, holding time, heating rate, and cooling rate were considered the control factors, while shrinkage, flexural strength, and process feasibility were the study responses. In addition, the flexural strength of materials was found between 25 and 85 MPa, while shrinkage fluctuated between 10 and 25%.
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The variation in biomarkers levels, such as L-methionine, can be an indicator of health problems or diseases, such as metabolism, neuropsychiatric disorders, or some virus infections. Thus, the development of accurate sensors, with low-cost and rapid response has been gaining increasing importance and attractiveness for the early diagnosis of diseases. In this regard, we have proposed a method for L-methionine electrochemical detection using a low-cost and simple arrangement of 3D-printed electrodes (working, reference, and auxiliary electrodes) based on polylactic acid/graphene filament (PLA-G), in which all electrodes were printed. The working electrode was chemically and electrochemically treated, showing a high electroactive area, with graphene edge plans exposure and better electron transfer when compared to the untreated electrode. An excellent analytical performance was obtained with a sensitivity of 0.176 µAL µmol-1, a linear dynamic range of 5.0 µmol L-1- 3000 µmol L-1 and limit of detection of 1.39 µmol L-1. The proposed device was successfully applied for L-methionine detection in spiked serum samples, showing satisfactory recovery values. This indicates the potentiality of the proposed arrangement of electrodes for the L-methionine detection in biological samples at different concentration levels.
Subject(s)
Electrochemical Techniques , Graphite , Electrodes , Methionine , Printing, Three-DimensionalABSTRACT
The use of hybrid manufacturing to produce bimodal scaffolds has represented a great advancement in tissue engineering. These scaffolds provide a favorable environment in which cells can adhere and produce new tissue. However, there are several areas of opportunity to manufacture structures that provide enough strength and rigidity, while also improving chemical integrity. As an advancement in the manufacturing process of scaffolds, a cooling system was introduced in a fused deposition modeling (FDM) machine to vary the temperature on the printing bed. Two groups of polylactic acid (PLA) scaffolds were then printed at two different bed temperatures. The rate of degradation was evaluated during eight weeks in Hank's Balanced Salt Solution (HBSS) in a controlled environment (37 °C-120 rpm) to assess crystallinity. Results showed the influence of the cooling system on the degradation rate of printed scaffolds after the immersion period. This phenomenon was attributable to the mechanism associated with alkaline hydrolysis, where a higher degree of crystallinity obtained in one group induced greater rates of mass loss. The overall crystallinity was observed, through differential scanning calorimetry (DSC), thermo gravimetric analysis (TGA), and Fourier transformed infrared spectroscopy (FTIR) analysis, to increase with time because of the erosion of some amorphous parts after immersion.