Particle Characterisation of Traditional Homeopathically Manufactured Medicine Cuprum metallicum and Controls

Background: Homeopathy is highly controversial. The main reason for this is its use of very highly dilute medicines (high homeopathic potencies, HHP), diluted beyond the Avogadro/Loschmidt limit. Research using several different methods has demonstrated the presence of particles, including nanoparticles of source material, in HHPs. This study aims to verify the results of a previous publication that detected the presence of particles in all dilutions. Methods: We used the Nano Tracking Analyzer (NTA) to examine dilutions of a commonly used homeopathic medicine, an insoluble metal, Cuprum metallicum, for the presence of particles. The homeopathic medicines tested were specially prepared according to the European pharmacopoeia standards. We compared the homeopathic dilutions/dynamizations with simple dilutions and controls including a soluble medicine. Results: We observed the presence of solid material in all preparations including HHPs (except for pure water). The measurements showed significant differences in particle sizes distribution between homeopathic manufacturing lines and controls. Conclusion: Homeopathic medicines do contain material with a specific size distribution even in HHPs diluted beyond the Avogadro/Loschmidt limit. This specificity can be attributed to the manufacturing and potentization process. This material demonstrates that the step-by-step process (dynamized or not) does not match the theoretical expectations in a dilution process. The starting material and dilution/dynamization method influences the nature and concentration of these NPs.

Stability of Rosmarinic Acid and Flavonoid Glycosides in Liquid Forms of Herbal Medicinal Products—A Preliminary Study

Peppermint leaf, sage leaf, thyme herb, and their preparations are common components of herbal medicinal products (HMPs). According to the European Pharmacopoeia guidelines, the above-mentioned plant substances are standardized for the content of essential oils, omitting polyphenols, which also have a significant impact on their activities. The aim of this study was to evaluate the stability of the predominant polyphenols—rosmarinic acid, luteolin-7-O-β-glucuronide, and eriocitrin—in selected commercial liquid HMPs containing thyme, sage, and peppermint under long-term, intermediate, and accelerated testing conditions. Qualitative and quantitative analyses of these polyphenols were performed by the previously optimized and validated HPLC-DAD method. Rosmarinic acid stability was better in hydroethanolic than in an aqueous solution. The effect of the solvent on the stability of luteolin-7-O-β-glucuronide and eriocitrin could not be determined and requires further investigation. The present study is the first to analyze the stability of these compounds in commercial herbal medicinal products. The expiration dates proposed by the manufacturers of the tested HMPs did not guarantee stable levels of all analyzed polyphenols throughout the stated period. However, this study is preliminary and requires continuation on a larger number of medicinal products.

Mycotoxins occurrence in medicinal herbs dietary supplements and exposure assessment

The multimycotoxin analysis of aflatoxins (AFs), zearalenone (ZEA), ochratoxin A (OTA), enniatins (ENNs) and beauvericin (BEA) was performed in 85 samples of medicinal herbs dietary supplements. The samples were classified in 64 samples of one herbal ingredient and 21 mixed samples. The extraction was performed by QuEChERS method and the determination by liquid chromatography coupled to ion-trap tandem mass spectrometry (LC–MS/MS-IT). Then, the risk characterization to mycotoxins through the consumption of medicinal herbs dietary supplements was assessed. The results showed that ZEA, OTA, ENNs and BEA showed in the samples with incidences between 1 and 34%, being ENNB the most detected mycotoxin. Mycotoxins contents ranged from LOQ to 3850.5 µg/kg while the mean of positives samples were 65.5 µg/kg (ENNA), 82.7 µg/kg (ENNA1), 88.7 µg/kg (ENNB), 324.9 µg/kg (ENNB1), 137.9 µg/kg (BEA) and 1340.11 µg/kg (ZEA), respectively. OTA was detected in one herbal mix tablet for insomnia at concentration of 799 μg/kg. In herbal drugs the European Pharmacopoeia Commission has implemented limits of 2 µg/kg for AFB1 and 4 µg/kg for total AFs. In the present study AFs have not been detected in the analyzed medicinal herbs dietary supplements. The Estimated Daily Intakes (EDIs) values were calculated using a deterministic method, considering two exposure scenarios (lower bound (LB) and upper bound (UB)). The values obtained were in general far below the Tolerable Daily Intakes (TDIs) established. Graphical abstract

Twenty Years of The State Pharmacopoeia of Ukraine: The Experience of Establishing the First National Pharmacopoeia in The Post-Soviet Area

The quality and life expectancy of the population depends on the level of access to modern, high-quality, effective and evidence-based medical and pharmaceutical care. These types of care play a significant role in the pharmacotherapy of cardiovascular disease (CVD), which is one of the main medical, biological and socio-economic problems of society. CVDs cause 67% of all deaths in Ukraine. For comparison: in France and Japan, this component in the structure of mortality is 29%, in the United States - 31%. Heart attacks are one of the main nosologies that cause high mortality from COVID. The 1st October, 2021 marks 20 years since the introduction of the State Pharmacopoeia of Ukraine. The purpose of the study was to experience of creating the first national pharmacopoeia in the post-Soviet space. Ukraine, the first in the post-Soviet space, managed to create its own State Pharmacopoeia, which is fully harmonized with the European Pharmacopoeia and takes into account national specifics. The State Pharmacopoeia of Ukraine relies on its own National system of pharmacopoeial standard samples and pharmacopoeial program of professional testing of control laboratories as feedback from users. The State Pharmacopoeia of Ukraine is not funded by the state, and the Pharmacopoeia Center is a completely self-supporting structure. In general, the State Pharmacopoeia of Ukraine can be considered the best National Pharmacopoeia in the post-Soviet space.

Development of Garcinia kola capsules

Garcinia kola usually referred to as "bitter cola" is a tree found in the rainforests. Many studies have revealed the properties of its seeds: antimicrobial, analgesic, anti-inflammatory, hepato-protective, antidiabetic, antioxidant. In the West Region of Cameroon these seeds are mainly used against nausea and vomiting; unfortunately, the generalization or the widening of the use of these seeds encounters some problems: the production is seasonal (June to September), the plant only grows in a small area (the departments of Moungo and Mbam and Inougou), the long storage of the seeds is not possible (they harden quickly and become unfit for consumption). The non-toxicity of these seeds having already been demonstrated by Udenze et al in 2012, in this study we wanted to develop a galenic form that is easy to produce and likely to help better use this resource by circumventing these difficulties. Garcinia kola seeds purchased in the city of Bafia, were cleaned, crushed and dried for 2 days at the temperature of 30°C and finally ground. The powder obtained was used to prepare capsules. The powder, calibrated through a 125 sieve, was homogeneous and had a residual humidity of 4%; its flavonoid content was 28 mg quercetin equivalent per gram. The capsules contained 400 mg of seed powder and titrated 3 mg quercetin equivalent of flavonoids per unit. They have responded favorably to the pharmacotechnical tests recommended by the European Pharmacopoeia 5th edition and appear to be able to allow the use of Garcinia kola seeds everywhere and in any season.

EFFECT OF CHITOSAN FILM SURFACE STRUCTURE ON THE CONTACT ANGLE

The aim of this study was to evaluate the influence of the surface microstructure of chitosan films on the contact angle. Films without plasticising additives made of chitosan or regenerated chitosan were selected for the tests. A sessile drop method based on the European Pharmacopoeia was used to determine the contact angle. Due to the method of film production, the contact angle measurements were made on both the top and bottom surfaces of the film. For chitosan or regenerated chitosan films, the method of preparation slightly affected the difference in wettability between the top and bottom of the films, as confirmed by scanning electron microscopy. On the other hand, the wettability of the top and bottom of cellulose films varied greatly depending on the side of the film. Both chitosan and cellulose films had a homogeneous structure. There were differences in the microstructure between the top and the bottom of the sample in the cellulose film, a factor that affected the contact angle and thus the wettability of the surface.

Tablet Splitting in Elderly Patients with Dementia: The Case of Quetiapine

Quetiapine is an atypical antipsychotic approved for treating schizophrenia, bipolar depression, and mania but is frequently used in an off-label manner to control the behavioral and psychological symptoms of dementia in elderly patients with dementia. Due to the need to personalize doses for elderly patients with dementia, quetiapine tablet manipulation is widespread in hospital settings, long-term care facilities, and patient homes. The aim of this study was to assess the impact of the different splitting techniques on quetiapine fumarate tablets by analysing the obtained sub-divided tablets and to discuss compliance with the European Pharmacopoeia limits on whole and split tablets. Quetiapine fumarate tablets of two dose strengths were taken at random (in a number able to assure a power of 0.8 during statistical comparison) and were split with a kitchen knife or tablet cutter. The weight and the drug content were determined for each half tablet. The obtained data were compared to the European Pharmacopoeia limits. The differences between the different splitting techniques were statistically tested. Data showed that split tablets, independently of the dose strength and the technique employed, were not compliant with the European Pharmacopoeia specifications for both entire and subdivided tablets in terms of weight and content uniformity. Thus, such a common practice could have potential effects on treatment efficacy and toxicity, especially when also considering the fragility of the elderly target population in which polypharmacotherapy is very common. These results indicate a compelling need for flexible quetiapine formulations that can assure more accurate dose personalization.

Capsule Formulation Essay of Herbal Extracts of Trunk Bark of Anogeissus leiocarpus (DC) Guill. Et Perr. (Combretaceae) for the Treatment of Hypertension

Introduction: The trunks barks of Anogeissus leiocarpus contains multiple antihypertensive components and are, therefore, widely used for the treatment of hypertension. Objective: This study aimed to formulate capsules containing a freeze-dried aqueous extract of the trunk’s barks. Methodology: Three (03) capsule formulations were prepared using wet granulation from lyophilised aqueous extract of Anogeissus leiocarpus trunk bark, with different proportions of excipients including Corn starch used as the diluent, Polyvinylpyrrolidone K25 (PVP) used as binding agent and Magnesium stearate used as gliding agents. The filling of capsules was done using a semi-automatic capsule filler with empty capsules of size 3. The flow properties of the granules and the quality control were performed according to the European Pharmacopoeia 10th ed. Results/Discussion: All granules had good flow properties, and the F1 and F3 formulations had the best pharmaceutics characteristics according to the recommendations of the European Pharmacopoeia 10th ed. The mean levels of phenolic tracers were 0.039±0.0097 mg gallic acid equivalent per capsule (GAE/capsule) for the F1 formulation and 0.059±0.0063 mg GAE/capsule for the F3 formulation. Conclusion: This study allowed the galenic formulation of capsules based on extracts of good characteristic quality for the treatment of hypertension. Keywords: Anogeissus leiocarpus, extract, excipients, formulations, capsule

Determination of the degree of degradation of specific impurity B contained in the substance of the drug «Lomustine» by high-resolution HPLC–MS/MS method

A high-resolution HPLC–MS/MS method was proposed for the study of solutions of standards of specific impurity B contained in the substance of the drug «Lomustine», which is included in the List of Vital Medicines. A characteristic degradation product of specific impurity B, the content and quantity of which is not regulated by the European Pharmacopoeia, has been found.

Oligochitosan Hydrochloride: Preparation and Characterization

The methods commonly used for depolymerization of chitosan and preparation of oligochitosan are discussed. A synthetic approach to oligochitosan hydrochloride with a molecular weight below 16 kDa based on the treatment of parent industrial high molecular weight chitosan with a mixture of hydrochloric acid and hydrogen peroxide is described. A series of analytical protocols are used to determine the physicochemical properties and quality of resulting oligochitosan hydrochloride according to the European Pharmacopoeia 4.0.