Modeling and Analysis of Morphology of Injection Molding Polypropylene Parts Induced by In-Mold Annealing.

It is generally recognized that high-temperature treatments, namely annealing, influence the microstructure and the morphology, which, in turn, determine the mechanical properties of polymeric parts. Therefore, annealing can be adopted to control the mechanical performance of the molded parts. This work aims to assess the effect of annealing on the morphology developed in isotactic polypropylene (iPP) injection-molded parts. In particular, a two-step annealing is adopted: the polymer is injected in a mold at a high temperature (413 or 433 K), which is kept for 5 min (first annealing step); afterward, the mold temperature is cooled down at 403 K and held at that temperature for a time compatible with the crystallization half-time at that temperature (second annealing step). The characterization of morphology is carried out by optical and electronic scanning microscopy. The temperature of the first annealing step does not influence the thickness of the fibrillar skin layer; however, such a layer is thinner than that found in the molded parts obtained without any annealing steps. The second annealing step does not influence the thickness of the fibrillar skin layer. The dimension of spherulites found in the core is strongly influenced by both annealing steps: the spherulite dimensions enlarge by the effect of annealing steps. A model that considers spherulite and fibril evolutions is adopted to describe the effect of molding conditions on the final morphology distribution along the part thickness. The model, which adopts as input the thermo-mechanical histories calculated by commercial software for injection molding simulation, consistently predicts the main effects of the molding conditions on the morphology distributions.

Multi-Scale Simulation of Injection Molding Process with Micro-Features Replication: Relevance of Rheological Behaviour and Crystallization.

The possibility of tailoring key surface properties through the injection molding process makes it intriguing from the perspective of sustainability enhancement. The surface properties depend on the replication accuracy of micro and nanostructures on moldings; such an accuracy is enhanced with cavity temperature. The simulation of the injection molding process is very challenging in the presence of micro and nanostructures on the cavity surface; this does not allow for the neglect of phenomena generally considered not to influence the overall process. In this paper, a multiscale approach was proposed: in the first step, the simulation of the overall process was conducted without considering the presence of the microstructure; in the second step the outputs of the first step were used as an input to simulate the replication of the microfeature. To this purpose, a lubrication approximation was adopted, and the contribution of the trapped air, which slows down the polymer advancement, was accounted for. A modification of the viscosity equation was also proposed to describe the rheological behavior of isotactic polypropylene at very low temperatures. Concerning the microcavity filling simulation, the modification of the viscosity description at low temperatures consistently describes the process, in terms of polymer solidification. Concerning the replication accuracy, it increases with the cavity surface temperature, consistently with the experimental observations.

Correction: Speranza, V. et al. Hierarchical Structure of iPP During Injection Molding Process with Fast Mold Temperature Evolution. Materials 2019, 12, 424.

The correction reported in the following has to be applied to the paper [...].

Effect of Rapid Mold Heating on the Structure and Performance of Injection-Molded Polypropylene.

The tailoring by the process of the properties developed in the plastic objects is the more effective way to improve the sustainability of the plastic objects. The possibility to tailor to the final use the properties developed within the molded object requires further understanding of the relationship between the properties of the plastic objects and the process conduction. One of the main process parameters that allow adjusting the properties of molded objects is the mold temperature. In this work, a thin electrical heater was located below the cavity surface in order to obtain rapid and localized surface heating/cooling cycles during the injection molding process. An isotactic polypropylene was adopted for the molding tests, during which surface temperature was modulated in terms of values and heating times. The modulation of the cavity temperature was found able to control the distribution of relevant morphological characteristics, thus, properties along the sample thickness. In particular, lamellar thickness, crystallinity distribution, and orientation were analyzed by synchrotron X-ray experiments, and the morphology and elastic modulus were characterized by atomic force microscopy acquisitions carried out with a tool for the simultaneous nanomechanical characterization. The crystalline degree slightly increased with the cavity temperature, and this induced an increase in the elastic modulus when high temperatures were adopted for the cavity surface. The cavity temperature strongly influenced the orientation distribution that, on its turn, determined the highest values of the elastic modulus found in the shear layer. Furthermore, although the sample core, not experiencing a strong flow field, was not characterized by high levels of orientation, it might show high values of the elastic modulus if temperature and time during crystallization were sufficient. In particular, if the macromolecules spent adequate time at temperatures close to the crystallization temperature, they could achieve high levels of structuring and, thus, high values of elastic modulus.

Polymer Processing: Modeling and Correlations Finalized to Tailoring Plastic Part Morphology and Properties.

The analysis of polymer processing operations requires the description of simultaneous transient momentum and heat transfer down to material solidification. The aim of the analysis is to improve and, hopefully, optimize the final properties that are determined by the final morphology of the part. In this special issue, consisting of 1 review and 11 research articles detailing several polymer processing operations, experimental and numerical analyses have been conducted in order to identify and describe the main relevant phenomena, that affect the product morphologies and properties.

Process Induced Morphology Development of Isotactic Polypropylene on the Basis of Molecular Stretch and Mechanical Work Evolutions.

It is well known that under high shear rates polymers tend to solidify with formation of morphological elements oriented and aligned along the flow direction. On the other hand, stretched polymer chains may not have sufficient time to undergo the structuring steps, which give rise to fibrillar morphology. In the last decades, several authors have proposed a combined criterion based on both a critical shear rate and a critical mechanical work, which guaranties adequate time for molecular structuring. In this paper, the criterion, reformulated on the basis of critical values of both molecular stretch and mechanical work and adjusted to account for the unsteady character of the polymer processing operations, is applied to the analysis of a set of isotactic polypropylene injection molded samples obtained under very different thermal boundary conditions. The evolutions of molecular stretch and mechanical work are evaluated using process simulation. The results of the model reproduce the main characteristics of the morphology distribution detected on the cross sections of moldings, obtained under very different thermal boundary conditions, assuming that the critical work is a function of temperature.

Hierarchical Structure of iPP During Injection Molding Process with Fast Mold Temperature Evolution.

Mold surface temperature strongly influences the molecular orientation and morphology developed in injection molded samples. In this work, an isotactic polypropylene was injected into a rectangular mold, in which the cavity surface temperature was properly modulated during the process by an electrical heating device. The induced thermo-mechanical histories strongly influenced the morphology developed in the injection molded parts. Polarized optical microscope and atomic force microscope were adopted for morphological investigations. The combination of flow field and cooling rate experienced by the polymer determined the hierarchical structure. Under strong flow fields and high temperatures, a tightly packed structure, called shish-kebab, aligned along the flow direction, was observed. Under weak flow fields, the formation of ß-phase, as cylindrites form, was observed. The formation of each morphological structure was analyzed and discussed on the bases of the flow and temperature fields, experienced by the polymer during each stage of the injection molding process.

Hydrophobicity Tuning by the Fast Evolution of Mold Temperature during Injection Molding.

The surface topography of a molded part strongly affects its functional properties, such as hydrophobicity, cleaning capabilities, adhesion, biological defense and frictional resistance. In this paper, the possibility to tune and increase the hydrophobicity of a molded polymeric part was explored. An isotactic polypropylene was injection molded with fast cavity surface temperature evolutions, obtained adopting a specifically designed heating system layered below the cavity surface. The surface topology was characterized by atomic force microscopy (AFM) and, concerning of hydrophobicity, by measuring the water static contact angle. Results show that the hydrophobicity increases with both the temperature level and the time the cavity surface temperature was kept high. In particular, the contact angle of the molded sample was found to increase from 90°, with conventional molding conditions, up to 113° with 160 °C of cavity surface temperature kept for 18 s. This increase was found to be due to the presence of sub-micro and nano-structures characterized by high values of spatial frequencies which could be more accurately replicated by adopting high heating temperatures and times. The surface topography and the hydrophobicity resulted therefore tunable by selecting appropriate injection molding conditions.

Mechanical Properties Distribution within Polypropylene Injection Molded Samples: Effect of Mold Temperature under Uneven Thermal Conditions.

The quality of the polymer parts produced by injection molding is strongly affected by the processing conditions. Uncontrolled deviations from the proper process parameters could significantly affect both internal structure and final material properties. In this work, to mimic an uneven temperature field, a strong asymmetric heating is applied during the production of injection-molded polypropylene samples. The morphology of the samples is characterized by optical and atomic force microscopy (AFM), whereas the distribution of mechanical modulus at different scales is obtained by Indentation and HarmoniX AFM tests. Results clearly show that the temperature differences between the two mold surfaces significantly affect the morphology distributions of the molded parts. This is due to both the uneven temperature field evolutions and to the asymmetric flow field. The final mechanical property distributions are determined by competition between the local molecular stretch and the local structuring achieved during solidification. The cooling rate changes affect internal structures in terms of relaxation/reorganization levels and give rise to an asymmetric distribution of mechanical properties.

Designing in-vitro systems to simulate the in-vivo permeability of drugs.

In this work an engineering approach, consisting in an experimental procedure and a model to derive the data, was presented and applied to improve the testing methods of pharmaceuticals. The permeability of several active molecules have been evaluated across a synthetic membrane. The permeability of these drugs measured through the artificial membrane were successfully correlated to their in-vivo permeability. The relationship with in-vivo permeability was derived, and then a rule to design systems to simulate the intestinal absorption was proposed to reduce the need for expensive and ethical problematic in-vivo measurements.

Measurements of non-uniform water content in hydroxypropyl-methyl-cellulose based matrices via texture analysis.

The use of hydrogels in the preparation of controlled release pharmaceutical forms is extensively diffused. The main feature of these polymers is their ability to swell forming a gel layer when they enter in contact with fluids. Once the gel layer is formed, the drug contained in the matrix can easily diffuse ensuring a controlled release from the tablet. Measurement of water content within a hydrating matrix based on hydrogels is a key topic in the study of pharmaceutical solid dosage forms. The aim of this work is to evaluate the water content of swollen matrices composed by HPMC and theophylline both in axial and in radial direction, as a function of time, using a texture analysis. A relationship between water content and slope of the force-penetration curves has been obtained using a simplified system in which the water uptake is allowed only in radial direction, obtaining thus partially hydrated matrices with the water content varying only along the radial direction. Once the relationship has been validated, it has been applied in a more complex system in which the polymer swelling takes place in both axial and radial direction. Thus, using the texture analysis it has been possible to determine the water in each position within the hydrated matrices.

Pharmacokinetics of Remifentanil: a three-compartmental modeling approach.

Remifentanil is a new opioid derivative drug characterized by a fast onset and by a short time of action, since it is rapidly degraded by esterases in blood and other tissues. Its pharmacokinetic and pharmacodynamics properties make remifentanil a very interesting molecule in the field of 0anesthesia. However a complete and versatile pharmacokinetic description of remifentanil still lacks. In this work a three-compartmental model has been developed to describe the pharmacokinetics of remifentanil both in the case in which it is administered by intravenous constant-rate infusion and by bolus injection. The model curves have been compared with experimental data published in scientific papers and the model parameters have been optimized to describe both ways of administration. The ad hoc model is adaptable and potentially useful for predictive purposes.

Measurements of water content in hydroxypropyl-methyl-cellulose based hydrogels via texture analysis.

In this work, a fast and accurate method to evaluate the water content in a cellulose derivative-based matrix subjected to controlled hydration was proposed and tuned. The method is based on the evaluation of the work of penetration required in the needle compression test. The work of penetration was successfully related to the hydrogel water content, assayed by a gravimetric technique. Moreover, a fitting model was proposed to correlate the two variables (the water content and the work of penetration). The availability of a reliable tool is useful both in the quantification of the water uptake phenomena, both in the management of the testing processes of novel pharmaceutical solid dosage forms.

In vitro simulation of drug intestinal absorption.

In this work, a simple set-up was designed, realized and tested to evaluate the effect of intestinal absorption on the in vitro drug release studies. The conventional USP-approved dissolution apparatus 2 was equipped with an hollow fibers filter, along with the necessary tubing and pumps, to simulate the two-fluids real behavior (the gastro intestinal lumen and the gastro intestinal circulatory system). The realized set-up was characterized in term of mass exchange characteristic, using the theophylline as the model drug, also with the aid of a simple mathematical model; then the release kinetics of a controlled release tablet was evaluated in the conventional test as well as in the novel simulator. The concentration of drug in the release compartment (which simulates the gastric lumen) was found lower in the novel simulator than in the traditional one.

Microencapsulation effectiveness of small active molecules in biopolymer by ultrasonic atomization technique.

A method to produce biopolymeric (alginate) microparticles by ultrasonic assisted atomization, previously developed, has been applied to the production of microparticles loaded with a small active molecule (theophylline). Fine loaded alginate droplets have been cross-linked with divalent ions to produce microparticles. Once produced, the particles have been separated by centrifugation or filtration and then they have been dried. Drug release has been evaluated by dissolution tests, dissolving the dried particles in acidic solution at pH 1 for a given time and then at pH 7 to simulate the stomach and intestinal environment, respectively. The encapsulation efficiency and the drug loading have been investigated and the operating conditions have been changed to clarify the role of the transport phenomena on the overall process. To increase the drug loading, shorter separation time and better network's structure were identified as the key operating parameters to allow the process to gain interest from a practical point of view.

An engineering approach to biomedical sciences: advanced testing methods and pharmacokinetic modeling.

In this paper, the philosophy of a research in pharmacology field, driven by an engineering approach, was described along with some case histories and examples. The improvement in the testing methods for pharmaceutical systems (in-vitro techniques), as well as the proposal and the testing of mathematical models to describe the pharmacokinetics (in-silico techniques) are reported with the aim of pointing out methodologies and tools able to reduce the need of expensive and ethical problematic in-vivo measurements.

The influence of dissolution conditions on the drug ADME phenomena.

In this work, a review of the apparatuses available to mimic what happens to a drug (or to foodstuffs) once ingested is presented. Similarly, a brief review of the models proposed to simulate the fate of a drug administered to a living body is reported. Then, the release kinetics of extended release of diclofenac from a commercial enteric-coated tablet was determined both in a conventional dissolution tester (USP Apparatus 2, Method A) as well as in an apparatus modified to reproduce a given pH evolution, closer to the real one than the one suggested by USP. The two experimental release profiles were reported and discussed; therefore, they were adopted as input functions for a previously proposed pharmacokinetic model. The obtained evolutions with time of plasma concentration were presented and used to assess the effectiveness of the commercial pharmaceutical products. The importance of a correct in vitro simulation for the design of pharmaceutical dosage systems was thus emphasized.

Enteric micro-particles for targeted oral drug delivery.

This work is focused on production of enteric-coated micro-particles for oral administration, using a water-in-oil-in-water solvent evaporation technique. The active agent theophylline was first encapsulated in cellulose acetate phthalate (CAP), a pH-sensitive well-known polymer, which is insoluble in acid media but dissolves at neutral pH (above pH 6). In this first step, CAP was chosen with the aim optimizing the preparation and characterization methods. The desired release pattern has been obtained (low release at low pH, higher release at neutral pH) but in presence of a low encapsulation efficiency. Then, the CAP was replaced by a novel-synthesized pH-sensitive poly(methyl methacrylate-acrylic acid) copolymer, poly(MMA-AA). In this second step, the role of two process parameters was investigated, i.e., the percentage of emulsion stabilizer (polyvinyl alcohol, PVA) and the stirring power for the double emulsion on the encapsulation efficiency. The encapsulation efficiency was found to increase with PVA percentage and to decrease with the stirring power. By increasing the PVA content and by decreasing the stirring power, a high stable double emulsion was obtained, and this explains the increase in encapsulation efficiency found.

On the behavior of HPMC/Theophylline matrices for controlled drug delivery.

Design of systems for oral controlled release of drug could take advantages from the knowledge of which phenomena take place. In this work matrices obtained by powders compression (50:50, hydroxypropyl methylcellulose, a swelling hydrogel, and theophylline, a model drug) were immersed in water at 37 degrees C, allowing the water uptake and the drug release by lateral surface, confining the cylindrical matrices between glass slides. The tablets, after given immersion times, were withdrawn, cut in several annuli, and subsequently analyzed for the drug and the water concentration radial profiles. The data confirmed the pseudo-diffusive nature of the process, allowing to give a deep insight into the drug release process from swellable hydrogel matrices. In particular, it was confirmed the presence of nonhomogeneous gel layer, rich in water and poor in drug, with a profile of drug concentration which agrees well with a pseudo-diffusion phenomenon.

A general code to predict the drug release kinetics from different shaped matrices.

This work deals with the modeling of drug release from solid pharmaceutical systems (matrices) for oral delivery. The attention was paid to the behavior of matrices made of hydrogels and drug, and the modeling was devoted to reproduce all the relevant phenomena (water up-take, gel swelling, diffusivity increase, drug diffusion and polymer erosion). Thus, the transient mass balances (for both drug and water), with the proper initial and boundary conditions were written, and a generalized numerical code was formulated; it is able to describe several geometries (slab, sphere, infinite and finite cylinders; this latter was done by an approximation which reduces the 2D problem to an 1D scheme). The main phenomena observed in drug delivery from hydrogel-based matrix, i.e. polymer swelling and erosion, were taken into account. The code was validated by comparison with analytical solutions, available for some simplified situation, and then it was tested with some experimental data taken from literature.