Residual Solvent Research Articles

Biodegradation of 2-methylpentane in fluid fine tailings amended with a mixture of iso-alkanes under sulfate-reducing conditions.

Anaerobic microorganisms in Canada Natural Upgrading Limited (CNUL) fluid fine tailings (FFT) are sustained by residual solvent hydrocarbons. Although FFT are methanogenic in nature, sulfate-reducing microorganisms represent a significant portion of FFT bacterial community. In this study, we examined biodegradation of three iso-alkanes (2-methylbutane, 2-methylpentane, and 3-methylpentane), representing major iso-alkanes in paraffinic solvent, in CNUL FFT under sulfate-reducing conditions. During ∼1100 days of incubation, only 2-methylpentane was degraded partially, whereas 2-methylbutane and 3-methylpentane were not degraded. During active degradation of 2-methylpentane, the bacterial community was dominated by Anaerolineaceae followed by Syntrophaceae, Peptococcaceae, Desulfobacteraceae, and Desulfobulbaceae. The archaeal community was co-dominated by acetoclastic (Methanosaetaceae) and hydrogenotrophic (Methanobacteriaceae) methanogens. This study underlines the limited capability of the microbial community indigenous to CNUL FFT in degrading recalcitrant iso-alkanes under sulfate-reducing conditions.

Experimentation and optimization of laser waterless decontamination rate of residual organic solvents

Laser waterless decontamination is a widely researched area for the high pollution issue of residual organic solvents in industry and agriculture. In this research, a nanosecond pulsed laser was used to conduct waterless decontamination studies on organic solvent residues on the surface of optical glass. A single-factor test was designed using the decontamination rate (Y) as the response value and the laser power (X1), scanning speed (X2), and decontamination times (X3) as the influencing variables. The Raman spectrum reflected the decontamination effect of organic solvent decontamination using a waterless laser. The Box-Behnken response surface method (RSM) was used to design the experiments. The developed RSM was used to determine the link between laser parameters and decontamination rate, and optimum decontamination parameters were determined. In addition, the mathematical model and regression equation were established using Design-Expert. The findings demonstrate that residual solvent may be removed at a rate of up to 95.22%. Optimum values for laser power, scanning speed, and decontamination times are 130 W, 381 mm/s, and 10 times respectively.

Clustering of Tadalafil API Samples According to their Manufacturer in the Context of API Falsification Detection

This paper reports the results of the active pharmaceutical ingredient (API) fingerprint study, organised by the General European Official Medicines Control Laboratory Network (GEON), on tadalafil. A classical market surveillance study, evaluating compliance to the European Pharmacopoeia, was combined with a fingerprint study, the latter to obtain characteristic data for the different manufacturers, allowing the network laboratories to conduct authenticity tests for future samples, as well as to detect substandard and falsified samples.In total, 46 tadalafil API samples from 13 different manufacturers were collected. For all samples fingerprint data was collected through analysis of impurities and residual solvents, mass spectrometric screening, X-ray powder diffraction and proton nuclear magnetic resonance (1H-NMR). Chemometric analysis revealed that all manufacturers could be characterised based on the impurity, residual solvent and 1H-NMR data. Future suspicious samples in the network will therefore be analysed with these techniques in order to attribute the sample to one of the manufacturers. If the sample cannot be attributed, a more profound investigation will be necessary to reveal the origin of the sample. In cases where the suspect sample is claimed to be from one of the manufacturers included in this study, analysis can be limited to the test distinguishing that manufacturer.

Intranasal spray of cubosomal tizanidine hydrochloride for brain targeting: in vitro and in vivo characterisation

Tizanidine HCl (TH) is used as first-line therapy for the treatment of muscular spasm. The intranasal cubosomal delivery system of TH for site-specific delivery, i.e. CNS was developed. Cubosomes of TH were prepared using glyceryl monooleate (GMO) as a lipid, poloxamer 407 as stabiliser, and ethanol and polyethylene glycol 200 as co-solvent. Optimised cubosomes of TH were characterised for vesicle size, zeta potential, % drug entrapment, and mucin binding efficiency, which were found to be 50.22 nm, −6.39 mV, 69.28%, and 42.12%. It is also evaluated for CRYO-FESEM, CRYO-TEM, SAXS, residual solvent content, and in vitro drug release. Ex vivo permeation was also conducted at 7.4 and it indicates that almost 93.66% drug was diffused from a formulation in 6 h. Histopathological study of the optimised TH cubosomes suggests that the prepared formulation is non-toxic to the nasal mucosa. Pharmacokinetic and brain distribution study indicates targeted action of the formulated TH cubosomes.

Potential of The Tyrosinase Enzyme Inhibition by Standardized Ethanol Extract And Ethyl Acetate Fraction of Bengkoang Peel (Pachyrhizus erosus L.)

This study examined the tyrosinase inhibitory potential of bengkoang peel standardised ethanolic extract and ethyl acetate fractions. 450 g of bengkoang peel powder (Pachyrhizus erosus L.) was macerated with 96% ethanol for 2 x 24 h, filtered, and concentrated till viscous. Extract standardisation uses specific and non-specific parameters. Microplate colorimetric tyrosinase inhibition assays were performed. The result of plant determination identified the bengkoang peel as Pachyrhizus erosus (L.) Urb. The organoleptic test revealed a brownish-yellow viscous extract, fresh smell, and bitter taste. Ethanol-soluble extract was 47.60% and water-soluble 22.42%. Bengkoang peel ethanolic extract includes alkaloids, flavonoids, saponins, tannins, and steroids. The non-specific parameters showed loss of drying (9.71%), water content (7.28%), total ash (9.91%), acid-insoluble ash (3.68%), no residual solvent content, lead content (-0.2324±0.1729), cadmium content (-0.0841±0.3418), TPC of 1 x 101 CFU/g, and TYMC of 2.26 x 102 CFU/g. The ethanol extract (103.9263) and ethyl acetate fraction (81.8606) IC50 values of bengkoang peel decrease tyrosinase enzyme activity compared to control (25.1235 ppm). These results show that the ethanol extract met both particular and non-specific quality standards. Bengkoang peel ethyl acetate inhibited tyrosinase.

The rate of adaptive molecular evolution in wild and domesticated Saccharomyces cerevisiae populations.

Through its fermentative capacities, Saccharomyces cerevisiae was central in the development of civilisation during the Neolithic period, and the yeast remains of importance in industry and biotechnology, giving rise to bona fide domesticated populations. Here, we conduct a population genomic study of domesticated and wild populations of S. cerevisiae. Using coalescent analyses, we report that the effective population size of yeast populations decreased since the divergence with S. paradoxus. We fitted models of distributions of fitness effects to infer the rate of adaptive ( ) and non-adaptive ( ) non-synonymous substitutions in protein-coding genes. We report an overall limited contribution of positive selection to S. cerevisiae protein evolution, albeit with higher rates of adaptive evolution in wild compared to domesticated populations. Our analyses revealed the signature of background selection and possibly Hill-Robertson interference, as recombination was found to be negatively correlated with and positively correlated with . However, the effect of recombination on was found to be labile, as it is only apparent after removing the impact of codon usage bias on the synonymous site frequency spectrum and disappears if we control for the correlation with , suggesting that it could be an artefact of the decreasing population size. Furthermore, the rate of adaptive non-synonymous substitutions is significantly correlated with the residue solvent exposure, a relation that cannot be explained by the population's demography. Together, our results provide a detailed characterisation of adaptive mutations in protein-coding genes across S. cerevisiae populations.

Extraction of Novel Bioactive Peptides from Fish Protein Hydrolysates by Enzymatic Reactions

Bioactive peptides derived from fish the byproduct protein hydrolysate have wide potential as functional food ingredients. The preparation of bioactive peptides is commonly achieved via enzymatic hydrolysis; this is the most preferred method because it has high specificity, fewer residual organic solvents in the product, and it is usually carried out in mild conditions. The use of various enzymes such as proteases is widely practiced in the industry, yet there are various limitations as it is of high cost and there is a limited availability of food-grade enzymes in the market. Moreover, high-throughput purification and the identification analysis of these peptides are currently being studied to further understand the functionality and characterization of the bioactive peptides. This review mainly focuses on the novel bioactive peptides derived from fish protein hydrolysates from various fish wastes and byproducts. The hydrolysis conditions, source of hydrolysate, and amino acid sequence of these novel peptides are presented, along with their corresponding methods of analysis in purification and identification. The use of various enzymes yields novel peptides with potent bioactivities, such as antiproliferative, antimicrobial, antihypertensive, antiglycemic, antitumor, and antioxidative biological functions. The increasing interest in proteomics in marine and aquatic waste utilization continues due to these products’ bioactivity and sustainability.

Use of ultrafiltration/diafiltration for the processing of antisense oligonucleotides.

Ultrafiltration/diafiltration (UF/DF) has been the hallmark for concentrating and buffer exchange of protein and peptide-based therapeutics for years. Here we examine the capabilities and limitations of UF/DF membranes to process oligonucleotides using antisense oligonucleotides (ASOs) as a model. Using a 3 kDa UF/DF membrane, oligonucleotides as small as 6 kDa are shown to have low sieving coefficients (<0.008) and thus can be concentrated to high concentrations (≤200 mg/mL) with high yield (≥95%) and low viscosity (<15 centipoise), provided the oligonucleotide is designed not to undergo self-hybridization. In general, the oligonucleotide should be at least twice the reported membrane molecular weight cutoff for robust retention. Regarding diafiltration, results show that a small amount of salt is necessary to maintain adequate flux at concentrations exceeding about 40 mg/mL. Removal of salts along with residual solvents and small molecule process-related impurities can be robust provided they are not positively charged as the interaction with the oligonucleotide can prevent passage through the membrane, even for common divalent cations such as calcium or magnesium. Overall, UF/DF is a valuable tool to utilize in oligonucleotide processing, especially as a final drug substance formulation step that enables a liquid active pharmaceutical ingredient.

A microfluidic application for mass production of drug-loaded polymeric microspheres for a long-acting injectable with IVL-DrugFluidic®, a novel microfluidic microsphere manufacturing platform technology

Long acting injectables (LAIs) using polymeric microspheres has been developed to increase patient compliance and reduce side effects. Among many methods for manufacturing polymeric microspheres, microfluidics technology is known to have excellent characteristics in that the produced polymeric microspheres have perfect spherical shape without surface defect and uniform size, and thus have outstanding efficacy without initial burst. However, the mass production of polymeric microspheres was not realized by the inherent limitation that microfluidics is suitable for small quantity manufacturing. Overcoming such limitations, we could show mass production of finasteride-loaded polymeric microspheres (PLGA 7525) for LAIs using our microfluidic manufacturing platform technology, IVL-DrugFluidic®. The microfluidic channels used in manufacturing were optimized through computational fluid dynamics (CFD) simulation to minimize the flow variation between microchannels and eliminated disturbance outside of microchannels by resistance channels. In addition, the solvent removal was improved by applying the baffle and foam breaker system. Therefore, microspheres were mass-produced in the GMP manufacturing environment in perfect spherical shape, smooth surface, and even size distribution. The encapsulation efficiency was almost 100% and the residual solvent was under the Standard of regulation. In the clinical trial using microspheres mass-produced by IVL-DrugFluidic®, we confirmed that the drug release was stably maintained for a month, the target period without initial burst. It was also confirmed that the drug release by dose of microspheres was uniformly proportional. In conclusion, the microsphere manufacturing platform technology, IVL-DrugFluidic® has been proven to be an appropriate system for mass production of polymeric microspheres optimized for LAIs through physicochemical characteristics and clinical trial.

Characterization of exparel bupivacaine multivesicular liposomes

Exparel is a bupivacaine multivesicular liposomes (MVLs) formulation developed based on the DepoFoam technology. The complex composition and the unique structure of MVLs pose challenges to the development and assessment of generic versions. In the present work, we developed a panel of analytical methods to characterize Exparel with respect to particle size, drug and lipid content, residual solvents, and pH. In addition, an accelerated in vitro drug release assay was developed using a rotator-facilitated, sample-and-separate experimental setup. The proposed method could achieve over 80% of bupivacaine release within 24 h, which could potentially be used for formulation comparison and quality control purposes. The batch-to-batch variability of Exparel was examined by the established analytical methods. Four different batches of Exparel showed good batch-to-batch consistency in drug content, particle size, pH, and in vitro drug release kinetics. However, slight variation in lipid contents were observed.

La2O3 Filler's Stabilization of Residual Solvent in Polymer Electrolyte for Advanced Solid‐State Lithium‐Metal Batteries

Polymer solid electrolytes (SEs) with high safety and flexibility are ideal for advanced lithium‐metal solid‐state batteries (SSBs). Among various polymer SEs, polyvinylidene fluoride‐co‐hexafluoropropylene (PVDF‐HFP) polymer SEs have gained increased attention for their high dielectric constants, high ionic conductivity, and excellent flexibility. However, severe side reactions at the interface caused by the decomposition of residual DMF solvent significantly reduce the cycle life of PVDF‐HFP‐based SSBs. Herein, La2O3 nanoparticles are used as new inorganic fillers to form a PVDF‐HFP/LiFSI/La2O3‐40% composite polymer electrolyte (PVDF‐HFP/La2O3 CPE). Benefiting from the interaction between La2O3 and N,N‐dimethylformamide (DMF) solvent molecules, the cell cycling stability is greatly improved. In addition, the PVDF‐HFP/LiFSI solid electrolyte (PVDF‐HFP SE) containing 40 wt% La2O3 has the highest ionic conductivity of 1.33 × 10−3 S cm−1 at 25 °C. It also exhibits a higher lithium‐ion transference number of 0.52 and lower polarization. The PVDF‐HFP/La2O3 CPE here ensures high ionic conductivity and stable interface chemistry in SSB, demonstrating a promising application potential.

Solvent transport dynamics and its effect on evolution of mechanical properties of nitrocellulose (NC)-based propellants under hot-air drying process

Appropriate drying process with optimized controlling of drying parameters plays a vital role in the improvement of the quality and performance of propellant products. However, few research on solvent transport dynamics within NC-based propellants was reported, and its effect on the evolution of mechanical properties was not interpreted yet. This study is conducted to gain a comprehensive understanding of hot-air drying for NC-based propellants and clarify the effect of temperature on solvent transport behavior and further the change of mechanical properties during drying. The drying kinetic curves show the drying time required is decreased but the steady solvent content is increased and the drying rate is obviously increased with the increase of hot-air temperatures, indicating hot-air temperatures have a significant effect on drying kinetics. A modified drying model was established, and results show it is more appropriate to describe solvent transport behavior within NC-based propellants. Moreover, two linear equations were established to exhibit the relationship between solvent content and its effect on the change of tensile properties, and the decrease of residual solvent content causes an obvious increase of tensile strength and tensile modulus of propellant products, indicating its mechanical properties can be partly improved by adjustment of residual solvent content. The outcomes can be used to clarify solvent transport mechanisms and optimize drying process parameters of double-based gun propellants.

Abstract 3378: Rapid and efficient sample preparations for cell free DNA

Abstract The analysis of cell-free DNA (cfDNA) as a sensitive biomarker for cancer prognosis, diagnosis and monitoring resulted in a need for efficient and fast cfDNA isolation. The traditional cfDNA purification methods using chaotropic solvent to separate nucleic acids from plasma through column or magnetic bead purification processes are usually laborious and time consuming, involving multiple washing steps, and the residual organic solvent could be carried over to the elution solution that could cause downstream PCR inhibition. Herein, we developed a novel particle surface chemistry that can biochemically bind rapidly (&amp;lt;1min) and release nucleic acids rapidly (&amp;lt;1min) under different buffer conditions without needing chaotropic solvent. We further optimized the binding and elution buffer solutions that allow to isolate cfDNA from plasma within 5-10 minutes in the sample volumes from 1 ml to 4 ml. The real-time quantitative PCR indicated DNA extraction yields were comparable or slightly better than the traditional methods for both small and large volumes. The novel bead chemistry and the optimized binding and elution buffers are not only compatible to high throughput format but could also be applied to a variety sample types for rapid sample preparations. Citation Format: Zhiyang Zeng, Andrew Taft, Kasen Riemersma, Connor Fitzgerald, Mike Scurria, Spenccer Hermanson, Wenhui Zhou. Rapid and efficient sample preparations for cell free DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3378.

Highly Efficient 2D/3D Mixed-Dimensional Cs2PbI2Cl2/CsPbI2.5Br0.5 Perovskite Solar Cells Prepared by Methanol/Isopropanol Treatment

All-inorganic perovskite solar cells are attractive photovoltaic devices because of their excellent optoelectronic performance and thermal stability. Unfortunately, the currently used efficient inorganic perovskite materials can spontaneously transform into undesirable phases without light-absorption properties. Studies have been carried out to stabilize all-inorganic perovskite by mixing low-dimensional perovskite. Compared with organic two-dimensional (2D) perovskite, inorganic 2D Cs2PbI2Cl2 shows superior thermal stability. Our group has successfully fabricated 2D/3D mixed-dimensional Cs2PbI2Cl2/CsPbI2.5Br0.5 films with increasing phase stability. The high boiling point of dimethyl sulfoxide (DMSO) makes it a preferred solvent in the preparation of Cs2PbI2Cl2/CsPbI2.5Br0.5 inorganic perovskite. When the perovskite films are prepared by the one-step solution method, it is difficult to evaporate the residual solvent molecules from the prefabricated films, resulting in films with rough surface morphology and high defect density. This study used the rapid precipitation method to control the formation of perovskite by treating it with methanol/isopropanol (MT/IPA) mixed solvent to produce densely packed, smooth, and high-crystallized perovskite films. The bulk defects and the carrier transport barrier of the interface were effectively reduced, which decreased the recombination of the carriers in the device. As a result, this effectively improved photoelectric performance. Through treatment with MT/IPA, the photoelectric conversion efficiency (PCE) of solar cells prepared in the N2 atmosphere increased from 13.44% to 14.10%, and the PCE of the device prepared in the air increased from 3.52% to 8.91%.

Uniformity and process stability of the slot-die coated PTB7:PC71BM organic photovoltaic improved by solvent additives

In this study, the organic photovoltaics (OPVs) with bulk heterojunction (BHJ) structure based on the active layer of PTB7:PC71BM and fabricated by sheet-to-sheet slot-die coating process are prepared to evaluate the uniformity and process stability of the active layer on cell performance. Various solvent additives are mixed in the host solvent o-xylene for improving the performance of low band-gap based polymer system. The solvent additives as recipe will influence the drying rate as well as the nano-BHJ morphology of the active layer. The residual solvent left in the dried film plays an important role in determining the uniformity and performance of organic photovoltaics. Thus, we comparatively investigate the correlation between recipes using solvent additives and different substrate temperature on sheet-to-sheet (S2S) system. OPV with active areas of range from 1 × 0.3, 1 × 1, 1 × 2 to 1 × 4 cm2 are fabricated to verify the performance of the scale-up devices. The temperature-independent feature of substrate is demonstrated for the recipe of 1.5 vol% 1,8-diiodooctane (DIO) plus 1.5 vol% 1-chloronaphthalene (CN). Less performance loss of 2.7% is shown at the active area of 1 × 4 cm2 compared to that of 16.1% for the recipe of 3 vol% DIO. The results will facilitate the scalable commercialization due to several merits of broad process window of S2S slot-die coating process, high film uniformity and high reproducibility between batches, and high power conversion efficiency.

Evaluation of Green Solvents’ Applicability for Chromatic Reintegration of Polychrome Artworks

Organic solvents are commonly used in restoration treatments, including chromatic reintegration on polychrome artworks. They are often toxic, and their vapors have a high impact on the environment and restorers, possibly causing pathological conditions. Therefore, this study aims at defining a new green solvent that can be used for chromatic reintegration, maintaining the volatility and the desired physical–chemical properties. The dispersion forces value (Fd) of ethyl lactate was taken as reference for a comparison with the proposed solvents, since it was found to be the most used solvent for the dilution of Maimeri Restoration Colors (MRC) and Gamblin Conservation Colors (GCC). Based on the Teas fractional parameters, six solutions based on acetals and ethanol have been proposed and tested. They were mixed with both MRC and GCC, and applied on prepared canvases. The difference between the backgrounds made with reference solvent and the one made with the proposed alternatives was evaluated through spectrocolorimetric measurements. Fourier-transform infrared spectroscopy in the attenuated total reflectance mode (FTIR-ATR) was performed on the applied layers to evaluate the presence of residual solvent inside them, while the volatility of the solvents was assessed by performing gravimetric analysis. The study showed that acetals, acetals’ blends, and acetals–ethanol mixtures represent suitable alternatives for the dilution of Gamblin Conservation Color and Maimeri Restoration Colors.

Platform headspace gas chromatography method for high-throughput determination of residual solvents in pharmaceutical materials

Static headspace capillary gas chromatography (HSGC) has been employed to monitor the level of residual solvents in the pharmaceutical materials. Most of the HSGC methods, however, consume significant amounts of diluents and require considerable amount of sample preparation time. Accordingly, a HSGC method featured with fast turnaround time, and minimal amount of solvent use has been developed for the quantitative analysis of 27 residual solvents frequently used in the development and manufacturing processes of pharmaceutical industry. This HSGC-FID method employs a commercially available fused silica capillary column, a split injection (40:1), and a programmed temperature ramp. It was qualified for specificity, accuracy, repeatability/precision, linearity, LOQ, solution stability, and robustness using two representative sample matrices. The standards, samples and spiked samples were demonstrated to be stable for at least 10 days at room temperature in sealed headspace vials with a recovery of ≥ 93%. The method was also shown to be robust, and its performance was not affected by small changes of carrier gas flow rate, initial oven temperature or the headspace oven temperature. In this new approach, the analytical sample was prepared by dissolving the sample into 1 mL of the diluent and the standard solution was prepared by diluting 1 mL of the custom-made stock into 9 mL of the diluent whereas the traditional approach requires liters of the diluent, making the new approach environmentally friendly, sustainable, economical, agile, error-proofing and thus appropriate for a variety of pharmaceutical applications.

Assessment and Non-Destructive Evaluation of the Influence of Residual Solvent on a Two-Part Epoxy-Based Adhesive Using Ultrasonics

Polymers are increasingly being used in higher demanding applications due to their ability to tailor the properties of structures while allowing for a weight and cost reduction. Solvents play an important role in the manufacture of polymeric structures since they allow for a reduction in the polymer’s viscosity or assist with the dispersion of fillers into the polymer matrix. However, the incorrect removal of the solvent affects both the physical and chemical properties of polymeric materials. The presence of residual solvent can also negatively affect the curing kinetics and the final quality of polymers. Destructive testing is mainly performed to characterize the properties of these materials. However, this type of testing involves using lab-type equipment that cannot be taken in-field to perform in situ testing and requires a specific sample preparation. Here, a method is presented to non-destructively evaluate the curing process and final viscoelastic properties of polymeric materials using ultrasonics. In this study, changes in longitudinal sound speed were detected during the curing of an aerospace epoxy adhesive as a result of variations in polymer chemistry. To simulate the presence of residual solvent, samples containing different weight percentages of isopropyl alcohol were manufactured and tested using ultrasonics. Thermogravimetric analysis was used to show changes in the decomposition of the adhesive due to the presence of IPA within the polymer structure. Adding 2, 4, and 6 wt.% of IPA decreased the adhesive’s lap shear strength by 40, 58, and 71%, respectively. Ultrasonics were used to show how the solvent influenced the curing process and the final sound speed of the adhesive. Young’s modulus and Poisson’s ratio were determined using both the longitudinal and shear sound speeds of the adhesive. Using ultrasonics has the potential to non-invasively characterize the quality of polymers in both an in-field and manufacturing settings, ensuring their reliability during use in demanding applications.

Comparison of the performances of different drying enhancers for waterborne polyvinyl alcohol films

AbstractWaterborne polyvinyl alcohol (PVA) films show lower environmental impact but render high residual solvent on account of hydrophilicity of PVA and low volatility of water. Plasticizers have shown high potential to act as drying enhancers in some recent studies. Plasticizers triphenyl phosphate (TPP) and polyethylene glycol (PEG400) with their favorable chemical structures and relatively low molar masses are promising options. Their performances in drying waterborne PVA films are compared with the plasticizers used in earlier works, at different initial wet film thicknesses, polymer contents, enhancer contents, and enhancer molar masses. Films were solvent casted by drying PVA‐water solutions in a substrate. TPP causes maximum lowering of the residual solvent and does this at high drying rate corresponding to low initial wet film thickness and PVA content. The least value of residual solvent is 0.20% at optimum TPP loading. The next best residual solvent results of 0.21% and 0.59% are, respectively, exhibited by PEG400 and PEG6000, but at low drying rate for high wet film thickness, for both the enhancers; however, at high drying rate for low wet film thickness anomalous skinning increased the residual solvent. At 0.51%, Capstone FS‐63 also gives good results and at high drying rate. Their relative performances are correlated to the viscosity of cast solutions, glass transition temperature of films (DSC), and chemical structures of the polymer and enhancers. TPP thus proved to be most effective. SEM showed dense films and disappearance of defects with optimum loading of TPP, and TGA/DTG showed thermally stable coatings. In spite of the higher cost of TPP it can have useful specialized applications that exploit its excellent flame retardance features.

SISTEM JAMINAN KEAMANAN PANGAN BERDASARKAN FSSC 22000 versi 5.1 / ISO TS 22002-4 PADA PROSES PRINTING DI INDUSTRI FLEXIBLE PACKAGING

A HACCP analysis of the printing process at one of the process steps in the Flexible packaging industry has been carried out as a hazard analysis step to determine the hazards that need to be controlled. The initial steps for making a flow chart have been carried out, which includes a flow chart of the printing process, which is the object of research. As per the ISO 22000 clauses that all food safety hazards that may occur related to the type of product, type of process, and existing process facilities are identified and recorded, a flowchart for the printing process is made in detail, including input, process, and output. This is to avoid product types, process types, and process facilities that can be overlooked during the hazard analysis process. In the HACCP analysis of the printing process, each food safety hazard has been identified and the acceptable level of the hazard has been determined. The results of the HACCP analysis on the printing process in this study have identified several process stages, from the input process to the output process. All of these stages have been analyzed for all hazards or sources of hazards, level of acceptance, hazard assessment, linkages with regulations or legislation, and determination of actions to prevent, reduce, or eliminate hazards. If the hazard assessment results in a "high" risk value and/or is related to regulations or legislation, then further analysis is carried out to determine whether a CCP is required or not. By carrying out a HACCP analysis of the printing process for the manufacture of flexible packaging, it is possible to determine the OPRP and CCP for the process, so that food safety guarantees in this process can be controlled and realized. The results of the validation process by monitoring the results of hazard measurements on residual solvent as a hazard from CCPs that have been determined in the printing process have shown that the process is under control and capable. The main findings in this study cannot be separated from the strong pillar support of GMP implementation, which is a rule or requirement from ISO/TS 22002-4 and FSSC requirements for the food packaging industry.