European Pharmacopoeia Research Articles

Xylometazoline base suitable for use in lipophilic drug products: development of production technology and analytical methods for quality control

The aim: development of the technology for obtaining the base of xylometazoline, suitable for the development of formulations in combination with essential oils. Development and validation of methods of control of related substances and assay of the obtained base of xylometazoline. Study of the stability of the obtained xylometazoline base under long-term and accelerated conditions. Materials and methods: experimental samples of xylometazoline base were obtained from commercially available xylometazoline hydrochloride and aqueous sodium hydroxide solution. The quality control of the obtained substance was carried out in accordance with the requirements of the internal specification. The analysis of raw materials of xylometazoline hydrochloride was carried out in accordance with the monograph of the European Pharmacopoeia on xylometazoline hydrochloride (Ph. Eur. 10.1, 1162 (01/2008)). Results: a technology for obtaining xylometazoline base from xylometazoline hydrochloride by the action of a 2 % solution of a strong base, namely sodium hydroxide, was developed. Developed and validated methods of quality control of the obtained xylometazoline base according to indicators of related substances and assay. The stability of the substance was studied for 1 year; the results of control under accelerated research conditions meet the requirements of the specification, which allows for establishing a shelf life of 2 years. Conclusions: the technology for obtaining xylometazoline base and quality control methods based on the monograph of the European Pharmacopoeia on xylometazoline hydrochloride was developed. The developed technology ensures the proper quality of the substance in accordance with the requirements of the internal specification. Analytical methods "related substances" and "assay" meet the established criteria during validation. The obtained results were later used to develop a medicine based on xylometazoline and eucalyptus oil – Eukazolin, nasal drops

Current and Future Pharmacopoeial Requirements for the Quality of Extemporaneous Medicinal Products: A Review of Regulatory Standards

INTRODUCTION. The organisation of extemporaneous compounding in pharmacies is currently considered to be a priority for the national healthcare system. Extemporaneous medicinal products used by patients should meet high quality, safety, and efficacy standards. Provision of consistent and science-based requirements for the quality of medicines, particularly those compounded in pharmacies, is a key area of concern for standardisation.AIM. This study aimed to analyse international experience and determine areas for the improvement of standardisation approaches of the State Pharmacopoeia of the Russian Federation to the quality of medicinal products compounded in pharmacies.DISCUSSION. The study investigated the common and distinctive properties of extemporaneous preparations compounded in pharmacies (and not subject to registration) and medicinal products manufactured by pharmaceutical companies. The authors analysed the requirements and recommendations for compounding and quality assurance of extemporaneous medicinal products provided by the regulatory and pharmacopoeial authorities of the Russian Federation, the Republic of Belarus, the European Union, the United Kingdom, the USA, and Canada. The United States Pharmacopeia includes circa 150 individual monographs for non-sterile compounded drug products with particular compositions and over 20 individual monographs for sterile compounded drug products. The European Pharmacopoeia requires that extemporaneous preparation should be organised within the quality assurance framework of a pharmacy after a proper risk assessment. In the Republic of Belarus, extemporaneous medicinal products are compounded in line with the requirements of the Good Compounding Practices and the State Pharmacopoeia of the Republic of Belarus, which provide rapid testing procedures for extemporaneous medicinal products.CONCLUSIONS. The study identified the following areas for the development of requirements for the quality of medicinal products compounded in pharmacies: the determination of rapid testing approaches; the development of pharmacopoeial monographs for active pharmaceutical substances used in extemporaneous compounding, with the Identification section supplemented with an additional subsection on pharmacy-specific analytical procedures; and the development of pharmacopoeial monographs for frequently used compounding formulae.

A new approach to drug intravenous compatibility research: the case of obstetric parenteral drugs

ObjectivesThe product information and literature does not provide confirmation of compatibility for co-administration of all commonly used drug pairs in obstetrics. However, there is a need for co-administration of these...

Testing of parenteral drug products for visible particles: comparison of the Ph. Eur. method with an alternative method using polarised light

ObjectivesParenteral drug products should be essentially free from visible particulate contamination. To ensure this, every batch produced must be subject to a 100% visual inspection. Monograph 2.9.20 of the European...

Characterisation of Aqueous Ultra-high Homeopathic Potencies: Nanoparticle Tracking Analysis.

Over the past decade, research using various methods has claimed the material nature, including nanoparticles (NPs), of high homeopathic potencies. The current study aims to verify these findings using NP tracking analysis (NTA). Six independent serial dilutions of commonly used homeopathic medicines-either soluble (Gelsemium, Pyrogenium, Kalium mur) or insoluble (Cuprum, Argentum, Silicea)-were prepared according to European Pharmacopoeia standards. We compared the homeopathic dynamisations (DYNs) in pure water with their potentised controls and with simple dilutions (DIL) up to 30cH/10-60. We also tested the influence of the container (glass or PET) on the solvent controls. We observed the presence of particles from 20 to 300-400 nm in all DYNs, DILs and controls, except in pure unstirred water. The sizes and size distributions of NPs in high homeopathic potencies were smaller than those in controls for soluble sources and larger for insoluble sources, even above 11cH. The opposite behaviour was observed in the number of NPs. When comparing DYN and DIL, the number, size, presence of aggregates or chains and brightness of NPs increased with DYNs, which was also observed above 11cH. Many NPs scattered light of low intensity, indicating the presence of material particles. The container had a significant effect on the number and size of NPs, indicating the involvement of the atmosphere and leaching processes. Homeopathic medicines contain NPs with specific properties, even when diluted beyond Avogadro's number. Homeopathic potentisation is not a simple dilution. The starting material, the solvent used, the type of container and the manufacturing method influence the characteristics of these NPs. The nature of these NPs is not known, but most likely they are a mixture of nanobubbles and elements from the atmosphere and container, including insoluble ones.

Paraspecific neutralization capacity of polyvalent snake antivenom against Montivipera wagneri venom

PurposeThis study aims to measure the paraspecific neutralization capacity of nationally produced HSGM polyvalent snake antivenom (HSGM-PSAV), produced using Macrovipera lebetina obtusa, Montivipera xanthina, and Vipera ammodytes montandoni venom, against the lethal effect of the venom of Montivipera wagneri, which is endemic to the Eastern Black Sea and Eastern Anatolia regions of Turkey. MethodsThe neutralization capacity of HSGM-PSAV against the lethal effect of M. wagneri venom was studied using the potency determination testing method specified in the Turkish and European Pharmacopoeia. Lethal dose 50 (LD50) values of the venoms used in immunization, M. wagneri venom in mice, and effective dose 50 (ED50) values of HSGM-PSAV against four types of venoms were calculated using two-fold dilutions. ResultsHSGM-PSAV neutralized the lethal effect of M. wagneri venom in mice. The ED50 of the HSGM-PSAV against M. wagneri venom was calculated as 304.42 LD50/mL. ConclusionAs a result of this in-vivo study, it was determined that HSGM-PSAV neutralized M.wagneri venom above the antivenom neutralization capacity threshold values (≥50 LD50/mL) specified in the Turkish and European Pharmacopoeia. This result is important preclinical data regarding the usability of HSGM-PSAV in the treatment of poisoning due to M. wagneri bites.

Development, Optimization, and Validation of an in vitro Cell-Based Bioassay to Determine the Biological Activity of Teriparatide (PTH1–34)

AbstractThis study aimed to establish an efficient in vitro cell-based assay to measure the activity of teriparatide (PTH1–34). In this study, a rat osteosarcoma cell line (UMR-106) was treated with various concentrations of PTH1–34, and the biological activity of PTH1–34 was determined by quantitatively measuring intracellular cyclic adenosine monophosphate levels using a time-resolved fluoroimmunoassay. A four-parameter fitting analysis was used to calculate the relative potency of the samples. The experimental conditions were optimized. The method's specificity, relative accuracy, precision, and linearity were validated. Our data suggested that this method had good specificity, a relative bias of relative accuracy ranging from −0.8 to 1.4%, a correlation coefficient for the linear regression equation of 0.9953, a geometric coefficient of variation for intermediate precision ranges from 2.0 to 3.5%, and a linear range of 50 to 150%. This method significantly improves the quality control and release inspection efficiency of PTH1–34 and may be further developed and validated as an alternative to the existing United States Pharmacopeia and European Pharmacopoeia inclusion methods. This method also provides a platform for the high-throughput screening of PTH1–34 analogs.

Effects of Vietnamese Balm (Elsholtzia ciliata (Thunb.) Hyland) Essential Oil on Growth Performance of Striped Catfish (Pangasianodon hypophthalmus) Juvenile stage

Graphical Abstract Highlight Research Gas chromatography-mass spectrometry identified major components of the essential oil, including (Z)-β-Farnesene (24.02%), neral (15.06%), geranial (15.02%), and β-ocimene (13.61%). Diets enriched with 5% Vietnamese balm leaf essential oils significantly improved the survival rate, feed conversion ratio, and feed efficiency. Diets enriched with 5% Vietnamese balm leaf essential oils significantly improved the weight parameters (average weight; weight gain; percentage weight gain; percentage specific growth rate; daily weight gain). Diets enriched with 5% Vietnamese balm leaf essential oils significantly improved the length parameters (average length; length gain; percentage length gain; percentage specific growth rate; daily length gain). Abstract Vietnamese balm (Elsholtzia ciliata) is a prominent herb in Vietnamese traditional medicine. This study investigated the impact of Vietnamese balm leaf essential oils on the growth of striped catfish (Pangasianodon hypophthalmus) in the juvenile stage. Essential oils were extracted using steam distillation, following European Pharmacopoeia guidelines. Gas chromatography-mass spectrometry identified the essential oil components. The experiment encompassed three treatments: 0% (control), 3%, and 5% of Vietnamese balm leaf essential oils in a completely randomized design. The results demonstrated a time and dose-dependent modulation of striped catfish growth by the essential oils. Diets enriched with 5% Vietnamese balm leaf essential oils significantly enhanced survival rate and growth, indicating potential as a fish feed additive. The essential oil yield was 0.83% dry weight, with major components including (Z)-β-Farnesene (24.02%), neral (15.06%), geranial (15.02%), and β-ocimene (13.61%). Additionally, the study emphasized the growth-promoting effects of herbal extracts on various growth parameters. Further investigations should explore the impact of Vietnamese balm essential oil on catfish immune response and disease resistance, providing a comprehensive understanding of its potential benefits.

Long-Term Stability of Glycopyrrolate Oral Solution Galenic Compound at Different Storage Conditions.

Glycopyrrolate is a competitive muscarinic receptor antagonist used in the treatment of sialorrhea, especially in pediatrics. Degradation research was conducted to better understand the stability of the active pharmaceutical ingredient (API). Using an HPLC-UV method, we evaluated the chemical stability of the oral solution of the galenic compound glycopyrrolate 0.5 mg/mL under different storage conditions. Method validation was performed according to the International Council for Harmonization (ICH) Q2(R2) guidelines. The results of the stability study of the galenic compound in different storage conditions, with the exception of those stored in glass containers at 45 °C for more than 3 months, were stable (100 ± 10% of the nominal concentration). The aim of this work was to study the stability of the galenic compound glycopyrrolate in two different types of containers and at three different storage temperatures. Glycopyrrolate showed degradation beyond the limits only in glass at 45 °C and after 2 months of storage. The results indicate that oral liquid dosage forms of glycopyrrolate are stable for at least 210 days when stored at room temperature or at 4 °C, in glass or PET, for at least 7 months, maintaining product quality according to the standards established by the European Pharmacopoeia, ensuring long-term coverage for pediatric patient therapies.

A global comparative analysis of guidelines for herbal medicines Pharmacopoeia and Good Manufacturing Practice, with a case study of Panax ginseng C.A Meyer

IntroductionThe use of herbal medicines is widespread, and ensuring their quality control, as guaranteed by pharmacopoeia and Good Manufacturing Practice (GMP) guidelines, has garnered significant attention. Discrepancies in quality standards across different regulatory agencies challenge the global marketing of herbal medicines and hinder public access to these products. Therefore, this research aims to compare pharmacopeia on Panax ginseng C.A. Meyer (P. ginseng) and GMP guidelines for herbal medicines to provide an evidence-based understanding of quality control standards. MethodsDefinitions of herbal medicines across regulatory authorities, including the World Health Organization (WHO), Pharmaceutical Inspection Co-operation Scheme (PIC/S), European Union (EU), China, Japan, South Korea, and Vietnam, were collected. Additionally, pharmacopeial standards on Panax ginseng case study were analysed, focusing on aspects such as origin, identification, testing methods, extractives, assay, purity, and drug information. The study also compared GMP requirements for herbal medicines, which included personnel, premises and equipment, documentation, production, quality control, contract manufacturing and analysis, complaints and product recall, and self-inspection. ResultsDefinitions of herbal medicines are similar among the WHO, PIC/S, and the EU, while distinct definitions based on scientific evidence and traditional practices were presented in China, Japan, South Korea, and Vietnam. Pharmacopeia standards varied across regulatory agencies, as evidenced by the P. ginseng case study. However, testing methods closely resembled each other between China and Vietnam, as well as between Japan and South Korea. Among pharmacopoeias, the WHO monographs offered the most comprehensive drug information on P. ginseng. In contrast, the European Pharmacopoeia lists such details separately in a P. ginseng assessment report. Regarding GMP requirements, although examined components varied among regulatory agencies, significant resemblances exist between the GMP guidelines of PIC/S, the EU, and South Korea, and between those of the WHO and Vietnam. ConclusionsDisparities in quality standards across jurisdictions highlight the necessity for international collaboration to achieve harmonization. Harmonizing these standards aims to promote the global availability of standardized herbal medicinal products, benefiting public health.

The Development of One New Normal Phase Liquid Chromatography Method and Thermodynamic Investigation of Olodaterol Hydrochloride Enantiomer.

In order to improve and replace the enantiomer method outlined in the olodaterol hydrochloride draft monograph (From the European Pharmacopoeia forum), one new, simple, and fast enantioselective normal phase high-performance liquid chromatography chiral method was developed on polysaccharide-based Chiral MX (2) (4.6 × 250 mm, 5 μm) column. n-Hexane, ethanol, and diethylamine in the ratio of 40:60:0.1 (V/V/V) were selected as mobile phase at a flow rate of 0.8 mL/min, and the detection was performed on a photodiode array detector at 225 nm with 5 μL injection volume. The column temperature was set at 40°C for better peak shape and sensitivity. The analysis time can be shortened to 15 min, whereas the resolution between enantiomer and olodaterol was found to be even more than 10.0, which was far better than that obtained with the reported method in this draft monograph. The developed chiral method was validated in accordance with ICH Q2 (R1), including specificity, LOD&LOQ, precision, linearity, accuracy, and robustness. Thereby, the proposed method was demonstrated to be suitable for the determination of enantiomer inolodaterol hydrochloride bulk drug and drug product. Besides, the thermodynamic parameters were evaluated on the basis of Van't Hoff plots that was used to explain correlative chiral recognition mechanisms with the chiral stationary phase.

A three-years survey of microbial contaminants in industrial hemp inflorescences from two Italian cultivation sites

BackgroundThe use of industrial Cannabis sativa L. for recreational, cosmeceutical, nutraceutical, and medicinal purposes has gained momentum due to its rich content of valuable phytochemicals, such as cannabidiol (CBD) and cannabigerol (CBG). However, there are concerns regarding the risk of microbial contamination in plants grown outside controlled environments. Microbes associated with hemp can be either epiphytes or endophytes and may pose a risk of infectious illness for humans.MethodsSeven Italian hemp genotypes, including Bernabeo, Carmagnola, Carmaleonte, Codimono, CS, Eletta Campana, and Fibranova, were cultivated in two distinct geographic locations, Catania and Rovigo, for three consecutive years from 2019 to 2021. Total aerobic microbes (TAMC), total combined yeasts/moulds (TYMC), the presence of bile-tolerant Gram-negative bacteria, and the absence of Escherichia coli and Salmonella spp. were evaluated and compared. The main phytocannabinoid content was measured and correlated with microbial contamination.ResultsMost samples analyzed in this study did not meet the European Pharmacopoeia microbiological limits. The detection of potential pathogens, such as E. coli and Salmonella spp., in the samples indicates that the use of inflorescences may represent a possible source of infection. Microbial contamination varied among harvesting seasons and production sites, with agroclimatic conditions influencing microbial load and composition. The presence of potentially pathogenic bacteria was less associated with seasonal climate variability and more likely affected by sporadic contamination from external sources. CBD concentration exhibited a negative correlation with bile-tolerant Gram-negative bacteria and total yeasts/moulds levels. Samples with lower CBD content were more contaminated than those with higher CBD levels, suggesting a potential protective effect of this phytochemical on the plant.ConclusionsThe threshing residues (inflorescences, floral bracts, and leaves) of industrial hemp varieties represent a valuable product and a source of beneficial phytochemicals that warrants further exploration. While post-harvest sterilization methods may reduce microbiological risks, they may also degrade heat- and light-sensitive bioactive phytochemicals. The most promising strategy involves implementing best agronomic practices to maintain healthy and uncontaminated cultures. Rigorous monitoring and quality certification protocols are essential to mitigate the microbiological risk associated with the consumption of hemp-derived products.

Development of a versatile [68Ga]Ga-FAPI-46 automated synthesis suitable to multi-elutions of germanium-68/gallium-68 generators.

Gallium-68-labeled FAPI-46 has recently been proposed as a novel positron emission tomography imaging probe to diagnose and monitor a wide variety of cancers. Promising results from several ongoing clinical trials have led to a soaring demand for this radiotracer. Typical [68Ga]Ga-FAPI-46 labeling protocols do not cope with multiple generator elutions, leaving radiopharmacies unable to scale-up the production and meet the demand. Here, we propose a robust and efficient automated radiosynthesis of [68Ga]Ga-FAPI-46 on the Trasis miniAllinOne synthesizer, featuring a prepurification step which allows multiple generator elutions and ensures compatibility with a wide range of gallium-68 generators. Our approach was to optimize the prepurification step by first testing five different cationic cartridge chemistries. Only the strong cationic exchange (SCX) cartridges tested had sufficient affinities for quantitative trapping of >99.9%, while the weak cationics did not exceed 50%. Packaging, rinsing, or flowing of the selected SCX cartridges was not noticeable, but improvements in fluidics managed to save time. Based on our previous development experience of [68Ga]Ga-FAPI-46, radiolabeling optimization was also carried out at different temperatures during 10min. At temperatures above 100°C, radiochemical yield (RCY) > 80% was achieved without significantly increasing the chemical impurities (<5.5μgmL-1). The optimized sequence was reproducibly conducted with three different brands of widely used generators (RCY >88%). A comparison with radiosyntheses carried out without prepurification steps was also conclusive in terms of RCY, radiochemical yield, and chemical purity. Finally, high-activity tests using elutions from three generators were also successful for these parameters. [68Ga]Ga-FAPI-46 was consistently obtained in good radiochemical yields (>89%, n = 3), and the final product quality was compliant with internal specifications based on European Pharmacopoeia. This process is suitable for GMP production and allows scaling-up of routine productions, higher throughput, and, ultimately, better patient care.

Understand the Stabilization Engineering of Ascorbic Acid, Mapping the Scheme for Stabilization, and Advancement.

Vitamin C is extensively used in cosmetic formulation, howbeit stability is the supreme demerit that limits its use in beautifying products. Numerous techniques are being employed to inhibit the degradation of vitamin C caused by formulation components to facilitate the use in skin rejuvenating products. Diverse materials are being exercised in formulation to stabilize the ascorbic acid and ingredients selected in this formulation composition help for stabilization. The initial stable prototype is developed and further optimization is accomplished by applying the design of experiment tools. The stable pharmaceutical formulations were evaluated for the evaluation parameters and designated as two optimized formulations. The analytical method for the assay of ascorbic acid from the United States pharmacopeia and the related substance method from European pharmacopeia has been modified to be used for cream formulation. The DoE design exhibited that the stability of formulation is impacted by citric acid and tartaric acid but not by propylene glycol and glycerin. The analysis results of topical formulations for the evaluation parameter exhibited satisfactory results. The in-vitro release study method has been developed, optimized, and validated to fit the analysis. The in-vitro studies have been performed for selected compositions and both the formulation has similar kinds of release patterns. The stability study as per ICH guidelines exhibited that the product is stable for accelerated, intermediate, and room-temperature storage conditions. The optimized formulation shows constant release and permeation of ascorbic acid through the skin. The formulation with the combinations of citric acid, tartaric acid, and tocopherol is more stable and the degradation of vitamin C has been reduced significantly. The beaucoup strategies in the unique composition help to protect the degradation by inhibiting the multitudinous degradation pathways.

APPLICATION OF MODERN METHODS OF ANALYSIS FOR DETERMINATION OF POLLUTION AND IDENTIFICATION OF PLANT RAW MATERIALS

Quality control of herbal preparations is an important component to ensure the effectiveness and safety of their use. Phytochemical medicines are made from medicinal plant materials that may contain unwanted chemical compounds, so careful quality control must be performed to ensure their safety and efficacy. The success of quality control of herbal materials requires an integrated approach, i.e. a combination of various techniques and methods that allow analyzing the main classes of compounds. Various methods of analysis are used to overcome these difficulties. Today, the main chemical methods for determining the quality of medicinal products are chromatographic, in particular gas chromatography (GC), often combined with mass spectrometry (MS), liquid chromatography (HPLC), thin-layer chromatography (TLC), column chromatography (CC). Besides, HILIC is the optimal method for the analysis of polar and ionized compounds that are too strongly retained on polar stationary phases and/or poorly separated by standard chromatographic methods. TLC/HPTLC methods are traditionally used by the SPhU and the European Pharmacopoeia for identification of herbs and detection of impurities by visual assessment, as well as for semi-quantitative determination of compounds when comparing the intensity of the spot in the zone of the tested solution with spots in the zones of reference compounds. The mentioned methods have still remained the most acceptable for the identification of herbs, which is explained by the unique chromatographic profile of each plant or extract based on it. At the same time, the instrumental method of HPLC has advantages due to the possibility of quantitative determination of substances that fluoresce in UV or visible light. Nowadays, the direction of scientific research devoted to the optimization of the previously described analytical methods and the development of new ones for the identification of both herbs and herbal materials, as well as herbal remedies, becomes relevant. In addition, the development of methods for the quantitative determination of herbal compounds is a relevant scientific and practical direction.

An Alternative Microbiological Validation for an Online Water Bioburden Analyzer.

The Mettler-Toledo 7000RMS analyzer is a Bio-Fluorescent Particle Counter (BFPC) used to monitor real-time bioburden results from Purified Water (PW). Validation of the analyzer using 13 microorganisms and a low-intensity, fluorescent, polystyrene bead. During the execution of the validation, a laboratory water system that met Purified Water (PW) quality standards was connected to the 7000RMS, and a syringe pump was used to introduce various concentrations of microorganisms and fluorescent polystyrene beads to the analyzer. Samples were collected and tested via the traditional Membrane Filtration (MF) method and the Colony Forming Unit (CFU) plate count results were compared to the Auto-Fluorescent Unit (AFU) of the 7000RMS analyzer. The validation study was designed to follow the guidance in United States Pharmacopeia (USP) Chapter <1223 > (1), European Pharmacopeia (EP) Chapter 5.1.6 (2), PDA Technical Report 33 (3). Concepts and strategies were adapted from EP Chapter 2.6.12 Microbiological Examination of Non-sterile Products: Microbial Enumeration Tests, EP 10.2 (4), European Pharmacopeia Chapter 2.6.1 Sterility, EP 10.2 (5), USP Chapter <61> Microbiological Examination of Non-sterile Products: Microbial Enumeration Tests (6), USP Chapter <71> Sterility Tests (7), Japanese Pharmacopoeia (JP) General Information Chapter G8 Water: Quality Control of Water for Pharmaceutical Use (8). All pre-determined validation acceptance criteria for Accuracy, Specificity, Precision, Limit of Detection (LOD), Limit of Quantitation (LOQ), Linearity, and Range were met. Further, the 7000RMS demonstrated Performance Equivalence to the MF method per USP <1223> but characteristically lacked correlation to the CFU. This validation approach highlights the superior capabilities of the 7000RMS when compared against the traditional compendial MF testing method for PW.

Automated radiosynthesis of pharmaceutical grade [68Ga]Ga-NODAGA-Lys40-Exendin-4 and demonstration of its efficacy for use in patients

The radiosynthesis of pharmaceutical grade [68Ga]Ga-NODAGA-Lys40-Exendin-4 was accomplished in a fixed tubing-based module, EZ Modular-Lab Standard. Purification of the product via hydrophilic-lipophilic balance cartridge, yielded satisfactory results with radiochemical purity > 98%. The decay-corrected radiochemical yield (RCY) with 50 µg of Exendin-4[Lys40(NODAGA)] was (78.7 ± 0.8)%, which, by far, to the best of our knowledge, is the highest RCY reported till date, using an automated synthesizer. The quality control parameters were in accordance with that of gallium (68Ga) Edotreotide® Injections, featuring in the European Pharmacopoeia. Pre-clinical dosimetry studies in animal models, with co-administration of kidney protectant, demonstrates promising potential of the product towards clinical translation to insulinoma patients.Graphical abstract

Fabrication and characterization of cocoa butter-based caffeine fast-melting tablets.

Aim: The objective of this study was to develop and characterize the physical properties of fast-melting tablets (FMTs) using cocoa butter as the base and caffeine as the model drug.Method: The simple refrigerator freezing method was employed to prepare caffeine-loaded, FMTs from cocoa butter bases.Results: The F3 chosen formulation achieved a disintegration time of 1.20min±0.035, which falls within the specified limit set by the European Pharmacopoeia. The cumulative drug release data of F3, was 88.52 and 94.08% within 60 and 75min, respectively (NLT 85% as per US FDA requirement). All the other physical test standards for FMTs met the pharmacopeial specifications.Conclusion: Based on the findings, the simple refrigerator freezing method could be used to formulate FMTs.

Examination of Particulate Contamination in Parenteral Injections and Infusions Following Fluid Withdrawal Utilizing Conventional Needles and Filter Needles: Assessment of Compliance and Comparative Analysis

Particulate contamination, the unintentional presence of particles in parenteral fluids, is associated with potential risks such as phlebitis and thrombophlebitis. Recent guidelines recommend the use of filter needles when withdrawing parenteral fluid from vials with a rubber stopper. However, the literature is limited and lacks clarity regarding the advantages of filter needles over conventional needles. The aim of this study was to assess the compliance of parenteral fluids regarding particulate contamination after withdrawing fluid using both conventional needles and filter needles, following the guidelines of European Pharmacopoeia (Ph. Eur.) and United States Pharmacopoeia (USP). Visible particles were counted through visual inspection and sub-visible particles were quantified utilizing the light obscuration particle count test. Particle counts for both types of needles were compared to Ph. Eur. and USP standards and differences in particle contamination were assessed using a Mann-Whitney U test. Both types of needles demonstrated compliance with Ph. Eur. and USP standards regarding particulate contamination of visible and sub-visible particles. However, filter needles exhibited a significantly higher particle count for particles with a size of ≥25 µm compared to conventional needles (p = 0.0029). In conclusion, both types of needles demonstrate suitability for aspirating fluid from vials featuring rubber stoppers regarding particulate contamination. Nevertheless, non-filter needles are preferred for withdrawing fluid from vials with a rubber stopper over filter needles due to their lower cost.

Procedure for rapid determination of bile-tolerant gram-negative bacteria in drugs

The European Pharmacopoeia is a single reference study for the quality control of drugs. The official standards published within it provide a legal and scientific basis for quality control in the processes of drugs development, production and marketing. However, the long experience and the multitude of studies have demonstrated that medicinal forms represent unstable dispersed systems and can undergo various manifest or non-manifest changes, leading to drug incompatibilities. Along with the physico-chemical transformations, microbiological transformations can occur with the contamination of the final product with pathogenic, conditionally pathogenic or even saprophytic germs, especially medicines that do not undergo final sterilization or are not aseptically prepared. Microbial contamination of the drug can be an indicator of the production conditions; it can cause the instability of the product through the microbial decomposition of auxiliary substances, the alteration or definitive cancellation of the therapeutic effect of the active substances, the appearance of metabolites with toxic properties, especially those fractions of endotoxins on the wall cell of gram-negative bacteria with the development of allergenic, pyrogenic substances and the induction of the danger of local orgeneral infections. An important role is attributed to the group of bile-tolerant gram-negative bacteria as representatives of microorganisms that are inadmissible in one g/ml for the absence test and for the quantitative test &lt;10 NCP/g/ml (probable number of bacteria), inadmissible in non-sterile medicinal products, herbal medicinal products for oral use and extracts used in their preparation. Due to the diversity of medicinal forms in terms of content, method of application, and therapeutic action, these preparations fulfil the indispensable conditions for the growth of microorganisms, therefore a primary concern is to avoid microbial contamination from the technological phase to the administration phase in order to prevent complications associated with bacterial infections. The given study reveals the testing of the procedure for the rapid determination of inadmissible microorganisms in non-sterile medicinal products and herbal drugs for oral use and the extracts used in their preparation, especially microorganisms of the group Enterobacteriaceae spp.