Rationalisation of the purification process for a phage active pharmaceutical ingredient.

The resurgence of phage therapy, once abandoned in the early 20th century in part due to issues related to the purification process and stability, is spurred by the global threat of antibiotic resistance. Engineering advances have enabled more precise separation unit operations, improving overall purification efficiency. The present review discusses the physicochemical properties of impurities commonly found in a phage lysate, e.g., contaminants, phage-related impurities, and propagation-related impurities. Differences in phages and bacterial impurities properties are leveraged to elaborate a four-step phage purification process: clarification, capture and concentration, subsequent purification and polishing. Ultimately, a framework for rationalising the development of a purification process is proposed, considering three operational characteristics, i.e., scalability, transferability to various phages and duration. This guide facilitates the preselection of a sequence of unit operations, which can then be confronted with the expected impurities to validate the theoretical capacity of the process to purify the phage lysate.

Water as a green solvent for sustainable sample preparation: single drop microextraction of N-nitrosamines from losartan tablets.

Water, renowned for its sustainability and minimal toxicity, is an ideal candidate for environmentally friendly solvent-based microextraction. However, its potential as an extractant solvent in miniaturized sample preparation remains largely unexplored. This paper pioneers using water as the extraction solvent in headspace single-drop microextraction (HS-SDME) for N-nitrosamines from losartan tablets. Autonomous HS-SDME is executed by an Arduino-controlled, lab-made Cartesian robot, using water for the online preconcentration of enriched extracts through direct injection into a column-switching system. Critical experimental parameters influencing HS-SDME performance are systematically explored through univariate and multivariate experiments. While most previously reported methods for determining N-nitrosamines in pharmaceutical formulations rely on highly selective mass spectrometry detection techniques to handle the strong matrix effects typical of pharmaceutical samples, the water-based HS-SDME method efficiently eliminates the interfering effects of a large amount of the pharmaceutical active ingredient and tablet excipients, allowing straightforward analysis using high-performance liquid chromatography with ultraviolet detection (HPLC-UV-Vis). Under optimized conditions, the developed method exhibits linear responses from 100 to 2400 ng g-1, demonstrating appropriate detectability, precision, and accuracy for the proposed application. Additionally, the environmental sustainability of the method is assessed using the AGREEprep methodology, positioning it as an outstanding green alternative for determining hazardous contaminants in pharmaceutical products.

Analytical considerations for characterization of generic peptide product: A regulatory insight.

The Peptide therapeutics market was evaluated to be around USD 45.67 BN in 2023 and is projected to witness massive growth at a CAGR of around 5.63 % from 2024 to 2032 (USD 80.4 BN). Generic peptides are expected to reach USD 27.1 billion by 2032 after the patent monopoly of the pioneer peptides expires, and generic peptides become accessible. The generic manufacturers are venturing into peptide-based therapeutics for the aforementioned reasons. There is an abundance of material accessible regarding the characterization of peptides, which can be quite confusing for researchers. The FDA believes that an ANDA applicant may now demonstrate that the active component in a proposed generic synthetic peptide drug product is the "same" as the active ingredient in a peptide of rDNA origin that has previously been approved. To ensure the efficacy, safety, and quality of peptide therapies during development, regulatory bodies demand comprehensive characterization utilizing several orthogonal methodologies. This article elaborates the peptide characterization by segmenting into different segments as per the critical quality attribute from identification of the peptide to the physicochemical property of the peptide therapeutics which will be required to demonstrate the sameness with reference product based on the size of the peptide chain and molecular weight of the peptides. Article insights briefly on each individual technique and the orthogonal techniques for each test were explained. The impurities requirements in the generic peptides as per the regulatory requirement were also discussed.

A New Discovery on the Potential Stability of Ion-Selective Membranes: The Poison from Tetrahydrofuran.

Ion-selective electrodes (ISEs) have widespread use in the fields of clinical and environmental analyses. Tetrahydrofuran (THF) is the most used solvent for the preparation of modern ISEs, equipped with ion-selective membranes (ISMs). Until now, the influence of impurities in THF toward potentiometric instability of ion-selective membrane based ISEs was probably associated with the presence of either residual water or peroxide. To address this issue, most literature recommends redistilling THF prior to use in the preparation of the potentiometric membranes. Current study reveals that the actual THF impurity that is responsible for potential instability in the ISM includes products from the oxidation of THF, which contains the hydroxyl group and possibly carbonyl group with a boiling point of above 200 °C. The density functional theory calculation supported pathway of the chemical reaction of THF oxidation, hence, the chemical structure of the uncertain impurities was predicted. The underlying reason for the deteriorating potential stability of the ISEs is proposed as the significant hydrophilicity of these impurities that affect the partitioning of the ion sensing components in the membrane, thus enhancing the leaching of the membrane components from the membrane phase. This finding explains why redistillation of aged THF is advised.

Multiple Traces of Families of Epoxy Derivatives as New Inhibitors of the Industrial Polymerization Reaction of Propylene.

In this study, the impact of ethylene oxide, propylene oxide, 1,2-butene oxide, and 1,2-pentene oxide on the polymerization of propylene at an industrial level was investigated, focusing on their influence on the catalytic efficiency and the properties of polypropylene (PP) without additives. The results show that concentrations between 0 and 1.24 ppm of these epoxides negatively affect the reaction's productivity, the PP's mechanical properties, the polymer's fluidity index, and the PP's thermal properties. Fourier transform infrared spectroscopy (FTIR) revealed bands for the Ti-O bond and the Cl-Ti-O-CH2 bonds at 430 to 475 cm-1 and 957 to 1037 cm-1, respectively, indicating the interaction between the epoxides and the Ziegler-Natta catalyst. The thermal degradation of PP in the presence of these epoxides showed a similar trend, varying in magnitude depending on the concentration of the inhibitor. Sample M7, with 0.021 ppm propylene oxide, exhibited significant mass loss at both 540 °C and 600 °C, suggesting that even small concentrations of this epoxide can markedly increase the thermal degradation of PP. This pattern is repeated in samples with 1,2-butene oxide and 1,2-pentene oxide. These results highlight the need to strictly control the presence of impurities in PP production to optimize both the final product's quality and the polymerization process's efficiency.

Effects of Impurities and Ageing on the Functional and Rheological Properties of Asphalts with Additives from Recovered and Pyrolysis-Processed Plastics.

This article is a continuation of work on the use of plastic waste (such as PP, PS, LDPE, HDPE, and their mixtures) processed in the proprietary pyrolysis process as asphalt additives. The article carried out detailed tests of the mixes of selected additives with pen-graded bitumen 50/70, taking into account, among others, the influence of impurities and the ratio of PE to PP in the additives as well as short- (RTFOT) and long-term (RTFOT + PAV) ageing. An extensive research program was carried out, including functional and rheological tests in a wide range of temperatures. First, tests of stability and adhesion to various types of aggregates were carried out, demonstrating the usefulness of the proposed additives. Then, the elastic recovery and the impact of technological ageing on penetration, Fraass breaking temperature, and plasticity range were assessed. The same binder mixes were subjected to rheological tests in a wide range of technological and operational temperatures, assessing, among others, viscosity, the norm of the complex shear modulus, elastic recovery and compliance in the MSCR test, and stiffness in the bending beam rheometer. This entire class of tests was carried out for clean samples and those containing impurities, indicating their impact on individual material parameters.

Real biofuel and fossil-fuel soot combustion activities in active and passive regeneration of diesel/gasoline particulate filters under different O2/NOx concentrations.

In this work, we aim to investigate and compare the combustion reactivities of real biofuel soot and fossil-fuel soot in the active and passive regeneration conditions of DPF and GPF through temperature-programmed oxidation (TPO). Higher reactivity of biofuel soot is achieved even under GPF conditions with extremely low oxygen concentration (~ 1%), which provides a great potential for low-temperature regeneration of GPF. Such a result is mainly attributed to the low graphitization and less surface C = C groups of biofuel soot. Unfortunately, the presence of high-content ashes (~ 47%) and P impurity in real biofuel soot hinder its combustion reactivity. TPO evidences that the O2/NOX-lacking conditions in GPF are key factors to impact the combustion of soot, especially fossil-fuel soot. This work provides some useful information for understanding real biofuel and fossil-fuel soot combustion in GPF and DPF regeneration and further improvement in filter regeneration process.

Characterization of Forced Degradation Products of Netarsudil: Optimization and Validation of a Stability-Indicating RP-HPLC Method for Simultaneous Quantification of Process-Related Impurities.

Objectives: The aim of this study is to examine resolution, identification, and characterization of forced degradation products of netarsudil by liquid chromatography-tandem mass spectrometry by validating a simple and sensitive high-performance liquid chromatography method for the resolution, identification, and quantification of two process-related impurities in netarsudil. Materials and Methods: Chromatographic separation was accomplished on a ZORBAX Eclipse XDB C18 (250 x 4.6 mm; 5 µ id) column at room temperature as the stationary phase and 257 nm as the detector wavelength with the mobile phase consisting of acetonitrile, methanol, and pH 4.6 phosphate buffer in 45:35:20 (v/v) at 1.0 mL/min flow rate in isocratic elution. Results: The method reported very sensitive detection limits of 0.008 µg/mL for impurity 1 and 0.003 µg/mL for impurity 1. The method produces a calibration curve linear in the concentration level of 25-200 for netarsudil and 0.025-0.2 µg/mL for impurities. The proposed method gives acceptable results for other validation parameters such as accuracy, precision, ruggedness, and robustness. The drug was subjected to various stress conditions such as acid, base, peroxide, and thermal and ultraviolet light to investigate the stability-indicating ability of the method. Considerable degradation was observed in stress studies, and the degradation products were well resolved from process-related impurities. The characterization of degradation products was performed on the basis of collision-induced dissociation mass spectral data, and the possible structures of the six degradation compounds of netarsudil were proposed. Conclusion: The outcomes of other validation studies were likewise satisfactory and proven adequate for the regular analysis of netarsudil and its process-related impurities in bulk drug and pharmaceutical dosage forms and can also be applied for the evaluation of the stress degradation mechanism of netarsudil.

N-nitrosamine impurity risk assessment in pharmaceuticals: Utilizing In vivo mutation relative potency comparison to establish an acceptable intake for NTTP.

The finding of N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) in marketed drugs has led to implementation of risk assessment processes intended to limit exposures to the entire class of N-nitrosamines. A critical component of the risk assessment process is establishing exposure limits that are protective of human health. One approach to establishing exposure limits for novel N-nitrosamines is to conduct an in vivo transgenic rodent (TGR) mutation study. Existing regulatory guidance on N-nitrosamines provides decision making criteria based on interpreting in vivo TGR mutation studies as an overall positive or negative. However, point of departure metrics, such as benchmark dose (BMD), can be used to define potency and provide an opportunity to establish relevant exposure limits. This can be achieved through relative potency comparison of novel N-nitrosamines with model N-nitrosamines possessing robust in vivo mutagenicity and carcinogenicity data. The current work adds to the dataset of model N-nitrosamines by providing in vivo TGR mutation data for N-nitrosopiperidine (NPIP). In vivo TGR mutation data was also generated for a novel N-nitrosamine impurity identified in sitagliptin-containing products, 7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo-[4,3-a]pyrazine (NTTP). Using the relative potency comparison approach, we have demonstrated the safety of NTTP exposures at or above levels of 1500 ng/day.

ChlorTox scale assessment, greenness, and whiteness evaluation of selective spectrophotometric analysis of dimenhydrinate and cinnarizine.

Nausea and vomiting are considered common series side effects induced by chemotherapy treatment in cancer patients. This annoying side effect can impair the patient's compliance to cancer treatment and affect their quality of life. Dimenhydrinate and cinnarizine in combined pharmaceutical dosage form is used to control chemotherapy induced nausea and vomiting in cancer patients. For safety, selective spectrophotometric methods based on novel dual resolution strategies were introduced to estimate dimenhydrinate and cinnarizine in presence of their harmful impurities namely benzophenone and 1- (diphenylmethyl)piperazine, respectively. These methods namely, dual ratio difference (DRD), dual ratio extraction (DRE) and dual absorbance extraction coupled with dual ratio extraction (DAE-DRE) were successfully performed to simultaneously analyze the drug of interests dimenhydrinate and cinnarizine in their pure form, synthetic mixtures and in market dosage form. Linearity ranges were 6.0-60.0 µg/mL and 3.0-30.0 µg/mL for dimenhydrinate and cinnarizine, respectively with good recovery% of Mean ± SD for all the proposed methods 99.82 ± 0.48, 99.79 ± 0.40, 100.14 ± 0.82, 100.03 ± 0.69, respectively. ICH guidelines were adhered in accordance with confirming validation of the proposed methods where fulfilling results were accomplished. Various unified greenness and whiteness assessment tools, such as the chlorTox scale, greenness index via spider chart, AGREE (The Analytical Greenness Metric), green certificate, and the RGB12 algorithm were employed in this research to assess the greenness and sustainability of the introduced UV-spectrophotometric methods in comparison to the reported HPLC method. As a result, these methods hold significant potential for utilization in the quality control department of pharmaceutical companies, contributing to enhanced pharmaceutical product analysis and overall sustainability practices.

Impurities in Active Pharmaceutical Ingredients and Drug Products: A Critical Review.

The presence of impurities in active pharmaceutical ingredients (APIs) and drug products represents a risk to patients' health. Such substances are related to diverse side effects and may have mutagenic potential. That's why it is necessary to establish acceptable limits for these by-products, to minimize the risk associated with medicinal therapy. This work focused on presenting a critical review of relevant points related to the presence of impurities in pharmaceuticals. The main legislation and guidelines from the FDA, EMA, ICH, and Pharmacopeias about the subject were evaluated, and recent articles related to the topic were searched in Scopus, ScienceDirect, PubMed, and Web of Science from 2013 to 2023. Additionally, the analytical techniques used for quantifying impurities were discussed, along with relevant tests for assessing the toxicological and mutagenic risks of these by-products. Recent legislation, including ICH Q3A (R2), ICH Q3B (R2), ICH M7 (R2), ICH Q3D (R2), ICH Q3C (R9), ICH Q3E, ICH Q6A, ICH M3 (R2), as well as FDA and EMA guidelines, highlights a comprehensive and effective framework for controlling impurities in pharmaceuticals. Despite this, there remains a lack of harmonization and standardized procedures across different regions. From the review of scientific literature, we observed that advancements in analytical techniques have significantly improved the sensitivity and selectivity in detecting impurities and degradation products. This underscores the ongoing commitment of health agencies and the pharmaceutical industry to ensure the safety and efficacy of medicinal products.

Mutagenic Azido Impurities in Drug Substances: A Perspective.

Contamination of drug products and substances containing impurities is a significant concern in the pharmaceutical industry because it may impact the quality and safety of medicinal products. Special attention is required when mutagenic impurities are present in pharmaceuticals, as they may pose a risk of carcinogenicity to humans. Therefore, controlling potential mutagenic impurities in active pharmaceutical ingredients to an acceptable safety limit is mandatory to ensure patient safety. As per the International Council for Harmonization (ICH) M7 (R2)3 Guideline, mutagenic impurities are those compounds or materials that induce point mutations. In 2018, the sartan class of drugs was recalled due to the presence of N-nitrosamine impurities, which are potential mutagens. In addition to the primary impurities being detected, this class of products, especially losartan, irbesartan and valsartan, have been identified as having organic azido contaminants, which are again highly reactive toward DNA, leading to an increased risk of cancer. These azido impurities form during the preparation of the tetrazole moiety via the reaction of a nitrile intermediate with sodium azide. Given that this is a newly raised issue in the pharmaceutical world, it should be noteworthy to review the related literature. Thus, this review article critically accounts for (i) the toxicity of azido impurities and the proposed mechanism of mutagenicity, (ii) the regulatory perspective, and (iii) the sources and control strategies used during the preparation of drug substances and (iv) future perspectives.

The continuing challenge of drug recalls: Insights from a ten-year FDA data analysis.

In this study we analyzed drug recall data from the U.S. Food and Drug Administration (FDA) over the period 2012-2023. We identified trends in the number of recalls initiated annually and their underlying causes. On average, 330 drug recalls are initiated each year, showing an overall increasing trend. The average duration of a recall, from initiation to termination date, was 1.3 years and each recall involved on average 400 000 product units, implying considerable resource demands and consequences for all stakeholders. The most frequent cause of these recalls was found to be impurities and contaminants (37 %), followed by control (28 %) and labeling/packaging (19 %) issues. Recalls of medicines causing serious health problems or death (class I), accounted for 14 % of the recall events. Continuous evaluation of recalls is expected to reduce their number, mitigate their impact on the healthcare system and improve drug safety.

Retrospective application of ICH M7 to anti-hypertensive drugs in Brazil: Risk assessment of potentially mutagenic impurities.

Potentially mutagenic impurities are likely to be formed in any drug substance, since their synthesis requires reactive intermediates which may also react with DNA. The ICH M7 guideline, which defines how to risk assess and control mutagenic impurities, was first published in 2014 and is not to be applied retrospectively; however, some impurities have been found above the permitted limits in drug products which were already on the market. This study assessed the implications of applying ICH M7 retrospectively to anti-hypertensive drugs marketed in Brazil by performing a risk assessment and establishing control strategies. The manufacturing processes of 15 drug substances were evaluated and 262 impurities were identified, from which 21% were classified as potentially mutagenic. Most of the impurities were identified below ICH M7 acceptable limits, except for impurities described in a pharmacopoeial monograph. Compendial specifications are defined based on scientific evidence and play an important role in setting quality and safety standards for pharmaceuticals, however there are opportunities for further alignment with ICH guidelines, aiming for a holistic assessment of the impurities profile to ensure the safety of medicines.

Determination of the safety of Halomonas sp. KM-1-derived D-ß-hydroxybutyric acid and its fermentation-derived impurities in mice and Japanese adults.

The use of halophilic bacteria in industrial chemical and food production has received great interest because of the unique properties of these bacteria; however, their safety remains under investigation. Halomonas sp. KM-1 intracellularly stores poly-D-ß-hydroxybutyric acid under aerobic conditions and successively secretes D-ß-hydroxybutyric acid (D-BHB) under microaerobic conditions. Therefore, we tested the safety of Halomonas sp. KM-1-derived D-BHB and the impurities generated during D-BHB manufacturing at a 100-fold increased concentration in acute tests using mice and daily intake of 16.0 g D-BHB in Japanese adults for 12 weeks. In the mice test, there were no abnormalities in the body weights or health of mice fed the purified D-BHB or its impurities. In the Japanese adult test, blood parameters and body condition showed no medically problematic fluctuations. These findings indicate that Halomonas sp. KM-1 is safe and can be used for commercial production of D-BHB and its derivatives.

Bilayer Porous Electrocatalysts for Stable and Selective Electrochemical Reduction of CO2 to Formate in the Presence of Flue Gas Containing NO and SO2.

The development of stable and selective electrocatalysts for converting CO2 to value-added chemicals or fuels has gained much interest in terms of their potential to mitigate anthropogenic carbon emissions. Most of the electrocatalysts are tested under pure CO2; however, industrial outlet flue gas contains numerous impurities, such as NO and SO2, which poison the electrocatalysts and alter the product selectivity. Developing electrocatalysts that are resistant to such impurities is essential for commercial implementation. Herein, we prepared bilayer porous electrocatalysts, namely, Sn, Bi, and In, on porous Cu foam mesh (Sn/Cu-f, Bi/Cu-f, and In/Cu-f) by a two-step electrodeposition process and employed these electrodes for the electrochemical reduction of CO2 to formate. It was observed that the bilayer porous electrocatalysts exhibited high CO2 reduction activity compared to catalysts coated on a Cu mesh. Among bilayer porous electrocatalysts, Sn/Cu-f and Bi/Cu-f electrocatalysts showed more than 80% faradaic efficiency (FE) toward formate production, with a formate partial current density of around -16 and -10.4 mA cm-2, respectively, at -1.02 V vs RHE. In/Cu-f electrocatalyst showed nearly 40% formate FE with formate partial current density of -15 mA cm-2 at -1.22 V vs RHE. We investigated the effect of NO and SO2 impurities (500 ppm of NO, 800 ppm of SO2, and 500 ppm of NO + 800 ppm of SO2) on these electrocatalysts' selectivity and stability toward formate. It was observed that the Bi/Cu-f electrocatalyst showed 50 h stability with 80 ± 5% formate FE, and Sn/Cu-f showed 18 h stability with above 80 ± 5% efficiency in the presence of NO and SO2 mixed with CO2. Furthermore, we studied the effect of CO2 concentration with Sn/Cu-f and Bi/Cu-f catalysts in the range of 15-100% CO2, for which formate FEs of 45-80% were observed.

The effects of impurities in carbide slag on the morphological evolution of CaCO3 during carbonation.

Carbide slag (CS) is a kind of solid waste generated by the hydrolysis of calcium carbide for acetylene production. Its major component is Ca(OH)2, which shows great potential in CO2 mineralization to produce CaCO3. However, the types of impurities in CS and their mechanisms for inducing the morphological evolution of CaCO3 are still unclear. In this work, the influence of impurities in CS on the morphology evolution of CaCO3 was investigated. The following impurities were identified in the CS: Al2O3, MgO, Fe2O3, SiO2 and CaCO3. Ca(OH)2 was used to study the influence of impurities (Al2O3 and Fe2O3) on the evolution of CaCO3 morphology during CS carbonation. Calcite (CaCO3) was the carbonation product produced during CS carbonation under varying conditions. The morphology of calcite was changed from cubic to rod-shaped, with increasing solid-liquid ratios. Moreover, rod-shaped calcite was converted into irregular particles with increasing CO2 flow rate and stirring speed. Rod-shaped calcite (CaCO3) was formed by CS carbonation at a solid-liquid ratio of 10:100 under a stirring speed of 600 rpm and a CO2 flow rate of 200 ml/min; and spherical calcite was generated during Ca(OH)2 carbonation under the same conditions. Al2O3 impurities had negligible effects on spherical CaCO3 during Ca(OH)2 carbonation. In contrast, rod-shaped CaCO3 was generated by adding 0.13 wt% Fe2O3 particles, similar to the content of Fe2O3 in CS. Rod-shaped calcite was converted into particulate calcite with increasing Fe2O3 content. The surface wettability and surface negative charge of Fe2O3 appeared to be responsible for the formation of rod-shaped CaCO3. This study enhances our understanding and utilization of CS and CO2 reduction and the fabrication of high-value rod-shaped CaCO3.

Nitrosamines crisis in pharmaceuticals - Insights on toxicological implications, root causes and risk assessment: A systematic review.

The presence of N-nitroso compounds, particularly N-nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects. This systematic review investigates their toxicity in active pharmaceutical ingredients (APIs), drug products, and pharmaceutical excipients, along with novel analytical strategies for detection, root cause analysis, reformulation strategies, and regulatory guidelines for nitrosamines. This review emphasizes the molecular toxicity of N-nitroso compounds, focusing on genotoxic, mutagenic, carcinogenic, and other physiological effects. Additionally, it addresses the ongoing nitrosamine crisis, the development of nitrosamine-free products, and the importance of sensitive detection methods and precise risk evaluation. This comprehensive overview will aid molecular biologists, analytical scientists, formulation scientists in research and development sector, and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

Hidden Impurities Generate False Positives in Single Atom Catalyst Imaging.

Single-atom catalysts (SACs) are an emerging class of materials, leveraging maximum atom utilization and distinctive structural and electronic properties to bridge heterogeneous and homogeneous catalysis. Direct imaging methods, such as aberration-corrected high-angle annular dark-field scanning transmission electron microscopy, are commonly applied to confirm the atomic dispersion of active sites. However, interpretations of data from these techniques can be challenging due to simultaneous contributions to intensity from impurities introduced during synthesis processes, as well as any variation in position relative to the focal plane of the electron beam. To address this matter, this paper presents a comprehensive study on two representative SACs containing isolated nickel or copper atoms. Spectroscopic techniques, including X-ray absorption spectroscopy, were employed to prove the high metal dispersion of the catalytic atoms. Employing scanning transmission electron microscopy imaging combined with single-atom-sensitive electron energy loss spectroscopy, we scrutinized thin specimens of the catalysts to provide an unambiguous chemical identification of the observed single-atom species and thereby distinguish impurities from active sites at the single-atom level. Overall, the study underscores the complexity of SACs characterization and establishes the importance of the use of spectroscopy in tandem with imaging at atomic resolution to fully and reliably characterize single-atom catalysts.

Effectiveness study of recrystallisation method in pharmaceutical salt production from processed salt with zero waste concept.

Indonesia's vast archipelago offers abundant seawater resources, holding the potential for salt production. Salt, a vital commodity in human life, typically contains sodium chloride and impurities like Ca2+, Mg2+, SO42-, and K+. Pharmaceutical salt is an industrial category adhering to pharmacopoeial standards regarding sodium chloride levels and impurity content, ensuring quality for drug preparations in Indonesia. Prior research indicates that recrystallisation, specifically evaporation crystallisation, enhances salt quality by increasing NaCl content. Chemical precipitating agents like NaOH and Na2CO3 can be introduced to improve salt purity further. This study aims to identify optimal conditions for pharmaceutical salt production from processed salt raw materials, considering crystallisation time, stirring speed, chemical additives (NaOH and Na2CO3), and double crystallisation stages. The method commences with pre-treatment, involving salt dissolution in distilled water to saturation, with the addition of precipitating agents as per designated variables. Precipitates formed from precipitating agents (NaOH and Na2CO3) are isolated through filtration. The filtrate undergoes evaporation crystallisation at 103 °C, varying between single and double crystallisation. Salt crystals are separated, dried, and weighed to calculate yield. Pharmaceutical salt is analysed for water content, NaCl, and impurities (Ca2+, Mg2+, SO42-, and K+). The optimal conditions for pharmaceutical salt production were double crystallisation with a 20 % excess of chemicals (NaOH and Na2CO3), 100 min of crystallisation time, and a stirring speed of 600 rpm. This yielded a 15 % NaCl content of 99.87 %, Mg2+ at 0 ppm, Ca2+ at 69.6 ppm, SO42- at 366 ppm, K+ at 370 ppm, and water content at 0.166 %. Notably, the pharmaceutical salt production process generates no waste, as byproducts like Mg(OH)2 and CaCO3 can be recycled and hold commercial value. However, it is essential to re-evaluate raw materials and technologies to address the market's high cost and competitiveness issues.