Hasil untuk "Pharmaceutical industry"

M. Cherubin, M. Cherubin, A. Delaunois et al.

IntroductionDrug-induced cardiotoxicity is one of the main causes of attrition due to safety in preclinical and clinical development; therefore, identifying novel assays and/or biomarkers to detect potentially harmful candidates is pivotal for the pharmaceutical industry. Over the past decade, microRNAs (miRNAs) have been proposed as alternative translatable biomarkers for cardiotoxicity. Although miRNAs could be useful for detection of cardiotoxicity, they are not routinely assessed in preclinical drug development.MethodsThe current study aimed to investigate dysregulation of miRNAs in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and their culture media after exposure to a set of cardiotoxic agents known to cause structural cardiotoxicity by different mechanisms of action. Dose-response analysis of intracellular miRNA expression was conducted after 72-hour incubation with 29 drugs, while the presence of miRNAs in the culture media was evaluated at 24-, 48-, and 72-hour post-treatment in response to 7 selected treatments.ResultsAs a result, we confirmed the upregulation of the following intracellular miRNAs across various drug classes: hsa-miR-96-5p, hsa-miR-126-3p, hsa-miR-133b, hsa-miR-146b-5p, hsa-miR-182-5p, hsa-miR-187-3p and hsa-miR-365a-5p. Interestingly, miRNAs expression in the cell culture media represented different patterns and magnitudes of upregulation, compared to the intracellular miRNAs. hsa-miR-133b, hsa-miRNA-184 and hsa-miR-208b-3p were found to be upregulated the most in the cell culture media.DiscussionThe combination of intracellular and secreted miRNAs in hiPSC-CM might expand the tools for early identification of structural cardiotoxicity in preclinical drug discovery and provide a potential link to circulating miRNAs in patients with drug-induced cardiotoxicity.

Jéssica Barreto Ribeiro dos Santos, Amanda Oliveira Lyrio, Felipe Ferré et al.

Objective: to evaluate the implementation, use, cost of treatment per patient-year and the bu dgetary impact of infliximab, vedolizumab and tofacitinib for the treatment of moderate to severe ulcerative colitis in the SUS. Methods: A retrospective cohort study was carried out using the Open Health Intelligence Situation Room, which originates from the SUS Ambulatory Information System. All patients with primary ICD-10 ulcerative colitis and using infliximab, vedolizumab or tofacitinib were included. The analysis period was from May 2020 to December 2022. Results: After incorporation into the SUS, the time for medicines to become available ranged from 7 to 20 months. Infliximab was the most used (55%), but vedolizumab spread faster, with approximately 60 new patients per month, followed by infliximab and tofacitinib with approximately 35 and 18 patients, respectively. Unit prices for medicines were lower than those proposed in the incorpora tion, except for tofacitinib in the last acquisition. In 2021, the cost per patient-year was similar for infliximab and vedolizumab. In 2022, vedolizumab had the highest cost. The budgetary impact of infliximab and vedolizumab was similar in the first year of imple mentation and both had a lower budgetary impact than estimated at incorporation. In the second year of infliximab implementation, the budgetary impact almost doubled due to the greater dissemination of the drug. Conclusion: This analysis presents real-world data, verifying the importance of monitoring the technologies incorporated by the SUS.

Linfeng Liu, Yujian Pang, Canliang Ma et al.

While C(sp3)-S bonds exist in many biologically active compounds, the direct catalytic C(sp3)-H thiolation remains elusive. Herein, we report a convenient and green C(sp3)-H thiolation approach mediated by using tetrabutylammonium decatungstate (TBADT) as a hydrogen atom transfer (HAT) photocatalyst. A wide range of C(sp3)-H bond-containing etheric, allylic, alkyl, ketonic, amidic substrates and sulfonyl-based SOMOphiles participated in the reaction, producing thioethers with high efficiency. The present protocol features green characteristics, such as being free of harmful oxidants and additives; step-economic; redox-neutral; and amenable to scale-up assisted by continuous-flow technology.

Mariya Mathew, Justyna Knapik-Kowalczuk, Mateusz Dulski et al.

<b>Objectives:</b> This study highlighted the key role played by high-pressure (HP) dielectric spectroscopic measurements of amorphous CBD to probe the molecular dynamics in order to examine the physical stability of the drug. The pharmacological properties of CBD assure that this can be a promising drug for the pharmaceutical industry. Hence, it is important to check the physical stability under elevated temperature and pressure conditions to understand the behavior of the drug under manufacturing conditions. <b>Methods:</b> This research investigated the molecular dynamics at various temperatures and pressures. We utilized the HP dielectric studies which are considered as an advanced and sensitive tool to determine both the molecular dynamics and the phase transformations. <b>Results:</b> This paper discusses the physical stability by analyzing the behavior of structural relaxation and crystallization tendencies of the amorphous drug under ambient and elevated pressure conditions. This study verified that amorphous CBD is highly physically stable at storage and elevated temperature conditions under ambient pressure. <b>Conclusions:</b> Accordingly, we examined the physical stability under elevated pressures at storage temperature, and we observed that the compression induced the crystallization of amorphous CBD. The breaking of weak hydrogen bonds present in the CBD might be the reason for this destabilization at elevated pressures. The least physical stability at high-pressure conditions was also confirmed by the broadening of the α-relaxation peak at high pressures.

D. Scott, A. Coyne, S. Hudson et al.

D. Braga, L. Maini, F. Grepioni

Felix Thoma, Dennis Schlehuber, Annette Somborn et al.

Due to several benefits regarding human health, the flavonoid rutin gains interest in nutrition and pharmaceutical industry. In order to satisfy high quality standards during cultivation and the final product, plants are grown increasingly in controlled environments with LED-technology as artificial light source. In this study the effect of various light settings on rutin content and biomass of Levisticum officinale was investigated. For continuous tracking of the biomass during cultivation, RGB-Images were taken. The actual biomass after harvest showed a strong positive correlation with the number of leaf-pixels detected via image processing (R2 = 0.937). Concerning the effect of UV-B radiation on rutin synthesis, time of synthesis was investigated. Two days after UV-B treatment a significant increase in rutin was observed. A short exposure time in combination with a high irradiance of 1 W m2 also showed positive effects on the rutin content in lovage. No significant effect of UV-B light on fresh weight was shown, but the combination of supplementary green light and high total photosynthetic photon flux density (PPFD) resulted in an increase of biomass.

Enes Dertli, Hüseyin Fakir, Ayşe Nur Bulut Güneş et al.

Inulin and fructooligosaccharides (FOS) are prominent functional components in the food industry due to prebiotic and other pharmaceutical properties. Inulin is a storage polysaccharide in various plants. FOS are naturally present in various plants and can be obtained by partial hydrolysis of inulin. In this study, ground and sieved chicory roots (Cichorium intybus L.) were used as starting material for inulin extraction under optimized conditions determined by Response Surface Methodology (RSM) with a Box-Behnken design. Optimum inulin extraction conditions from chicory roots were; temperature of 90 °C, extraction time of 30 min., and liquid-to-solid (LS) ratio of 10:1 mL/g. Inulin extract was further hydrolyzed to FOS by enzymatic or acid treatment, separately. Purification of inulin extract and FOS hydrolysate was performed by ultrafiltration with a 10 kDa membrane under the pressure of 2 bar with continuous stirring. As a result, inulin and FOS were obtained at 90% and 76% purity, respectively.

Mayra K. S. Monteiro, Mayara M. S. Monteiro, João M. M. Henrique et al.

Developing new products that satisfy performance and durability expectations while also addressing environmental concerns is possible through the reuse of residues produced by industrial processes, aiming to fulfill the principles of circular economy. In this study, we improved the performance of a carbon paste sensor by incorporating untreated (RC) and regranulated/thermally treated (RGC) cork, which are considered biomass residues from the cork industry. We explored the electroanalytical behavior of paracetamol in sulfuric acid solutions using cyclic voltammetry and differential pulse techniques. The cork-modified carbon paste sensors showed greater sensitivity towards paracetamol. Both modified sensors allowed for an excellent resolution in distinguishing the voltammetric responses of paracetamol in sulfuric acid, showing for both an increase in peak currents compared to the unmodified carbon paste electrode. The quantification of paracetamol without interference has proved to be a feasible operation for the RC- and RGC-modified carbon paste sensors; notably, the first showed the most favorable limits of detection (LD = 2.4112 µM) and quantification (LQ = 8.0373 µM) for paracetamol in the sulfuric acid solution, performing significantly better than the second (LD = 10.355 µM, and LQ = 34.518 µM). Finally, the practical utility of the proposed sensors was assessed by analyzing paracetamol in pharmaceutical samples, obtaining satisfactory results that were in line with those obtainable using high-performance liquid chromatography.

Maisa R P Araújo, L. Sá-Barreto, Taís Gratieri et al.

The pharmaceutical industry is set to join the fourth industrial revolution with the 3D printing of medicines. The application of 3D printers in compounding pharmacies will turn them into digital pharmacies, wrapping up the telemedicine care cycle and definitively modifying the pharmacotherapeutic treatment of patients. Fused deposition modeling 3D printing technology melts extruded drug-loaded filaments into any dosage form; and allows the obtainment of flexible dosages with different shapes, multiple active pharmaceutical ingredients and modulated drug release kinetics—in other words, offering customized medicine. This work aimed to present an update on this technology, discussing its challenges. The co-participation of the pharmaceutical industry and compounding pharmacies seems to be the best way to turn this technology into reality. The pharmaceutical industry can produce drug-loaded filaments on a large scale with the necessary quality and safety guarantees; while digital pharmacies can transform the filaments into personalized medicine according to specific prescriptions. For this to occur, adaptations in commercial 3D printers will need to meet health requirements for drug products preparation, and it will be necessary to make advances in regulatory gaps and discussions on patent protection. Thus, despite the conservatism of the sector, 3D drug printing has the potential to become the biggest technological leap ever seen in the pharmaceutical segment, and according to the most optimistic prognostics, it will soon be within reach.

R. Henderson, I. Cockburn

Puratchimani Renugadevi, Anandabaskar Nishanthi, Manickam Shanthi

Background: Doctors rely on drug advertisements provided by the pharmaceutical industry as an authentic source of drug information. However, they are found to be highly incomplete, biased, and inaccurate, thus leading to irrational drug use. Aims and Objectives: To assess the adherence of printed drug promotional literature (DPL) provided to private medical practitioners using the World Health Organization (WHO) guidelines for ethical drug promotion. Materials and Methods: In this cross-sectional study, the printed DPLs distributed to private practitioners by medical representatives in their outpatient clinics were randomly collected. The DPLs were categorized into full and reminder advertisements and were analyzed based on the WHO guidelines. Results: A total of 206 DPLs were collected, of which the majority (61.7%) were reminder DPLs. All the full DPLs had the generic and brand name, dosage form, and active ingredient (s). Therapeutic uses, manufacturer name, manufacturer address, dosage regimen, references, and side effects were mentioned in 60.8%, 60.8%, 13.9%, 8.9%, 10.1%, and 5.1% of them, respectively. Precautions, contra-indications, and interactions were present in only one full DPL. Concerning reminder DPLs, brand name, generic name, active ingredient (s), manufacturer name, and manufacturer address were mentioned in 100%, 96.9%, 96.1%, 52%, and 26.8% of them, respectively. Conclusion: Our study shows that none of the full DPLs and only one-fourth of reminder DPLs fulfilled all the WHO criteria. Due to rampant unethical drug promotional practices, it is essential to train doctors on critical evaluation of DPLs and stringent laws should be enforced to improve the quality of DPLs and mandate ethical drug promotion. [Natl J Physiol Pharm Pharmacol 2023; 13(11.000): 2341-2346]

C. Roberts

P. C. Allen, R. Fetterer

Rajesh Thipparaboina, Dinesh Kumar, R. Chavan et al.

A. V. Lezina, A. K. Whaley, A. O. Whaley et al.

Introduction. Medicinal plant raw materials, containing a wide range of various biologically active compounds, are of considerable interest as a likely source of new, pharmacologically active biologically active substances. One of the promising plants is Rhodiola quadrifida (Pall.) Fisch. &amp; C.A. Mey, since the raw materials contain phenolic compounds and their derivatives, which cause anti-inflammatory, antioxidant and anticarcinogenic effects. In addition, this plant has considerable popularity in folk medicine as a dietary supplement.Aim. Isolation of individual compounds from rhizomes and roots of Rhodiola quadrifida and subsequent determination of their structure by NMR and mass spectrometry for phytochemical profiling.Materials and methods. Rhizomes and roots of Rhodiola quadrifida, purchased in the pharmacy of St. Petersburg (place and time of procurement according to the information on the package – Altai (near Barnaul), in March 2019. The ethanol extract fractions (ethanol, hexane, butanol, and water) obtained during sequential liquid-liquid extraction were examined on a LC-20 Prominence instrument (Shimadzu, Japan) with an SPD-M20A diode array detector to determine the chromatographic profile. The most promising ethyl acetate fraction was purified by column chromatography on open glass columns with sorbents of different selectivity and preparative chromatography [Smartlina (Knauer, Germany)] with a spectrophotometric detector. The structure of the obtained individual compounds was determined by NMR (Bruker Avance III 400 MHz, Germany) and confirmed by low-resolution mass spectrometry [Flexar FX-15 (PerkinElmer, USA)].Results and discussion. During the study, 7 individual compounds were isolated from the rhizomes and roots of Rhodiola quadrifida, namely 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, caffeic acid, ethyl gallate, catechin, epicatechin and tyrosol. These compounds were isolated for the first time from the raw materials of Rhodiola quadrifida. They are the major compounds and can characterize the phytochemical profile of raw materials, as well as determine the direction of pharmacological activity.Conclusion. For the first time, Rhodiola quadrifida was isolated from raw materials and the structure of 7 majority compounds was proved by NMR spectroscopy and mass spectrometry, which can serve as a foundation for further study of this species of Rhodiola and targeted study of its pharmacological activity in vitro and in vivo, considering the individual phytochemical profile.

Olha Mykhailenko, Narzullo Boboevich Saidov, Liudas Ivanauskas et al.

Crocus sativus L. (Iridaceae) is the source of saffron, a traditional spice and herbal medicine, usually cultivated in Southwest Asia and the Mediterranean. Saffron is a new niche food and medicinal plant in Ukraine. An important area of production, namely the application of Good Agricultural and Collection Practice (GACP) principles for obtaining high-quality saffron raw materials for the pharmaceutical industry, has been evaluated. The study was conducted on a plantation in Lyubimovka village, Kherson Region in Ukraine, from 2016 to 2021. The research object was Crocus sativus and the quality management system in the cultivation and harvesting of medicinal plants. The Ukrainian legislation on herbal drug production introduced guidelines by the World Health Organization (WHO) ‘Good Agricultural and Collection Practice (GACP) for Starting Materials of Herbal Origin’ in 2012. The Guidelines are recommendatory and not mandatory. However, these principles ensure that appropriate quality herbal raw materials are obtained. Implementing GACP principles with the example of saffron includes a description of the plant, sowing material, primary processing, sowing conditions, transportation and storage, packaging, quality control, and documentation. The presented results reflect the entire production process and show the prospects for obtaining high-quality raw materials. The study suggests the results of implementing the WHO GACP guidelines to guarantee the traceability of herbal raw materials and their reliable quality.

P. Conrad

Rosana Pereira da Silva, Giovanna Sayuri Domingues Kawai, Fabio Ramos Dias de Andrade et al.

Calcium carbonate (CaCO₃) from the seaweed <i>Lithothamnium calcareum</i> is a suitable dietary supplement for the prevention of osteoporosis, due to its chemical composition. This study compared CaCO₃ from <i>L. calcareum</i> to CaCO₃ from oyster shell and inorganic minerals that are already used in the pharmaceutical industry. The Rietveld refinement of the XRD showed that the mineral fraction of <i>L. calcareum</i> is composed of aragonite (50.3 wt%), magnesian calcite (45.3 wt%), calcite (4.4 wt%), comin contrast to oyster shell and inorganic minerals, which contain only calcite. The morphology of <i>L. calcareum</i> carbonate particles is granular xenomorphic, which is distinct from the scalenohedral form of inorganic calcite and the fibrous and scale-like fragments of oyster shell. The crystal structures of aragonite and magnesian calcite, present in <i>L. calcareum</i>, have higher contents of oligoelements than the pure calcite in other materials. The isotopic composition (stable isotopes of carbon and oxygen) is heavy in the CaCO₃ from <i>L. calcareum</i> (δ¹³C = 1.1‰; δ¹⁸O = −0.1‰) and oyster shell (δ¹³C = −4‰; δ¹⁸O = −2.8‰) in marked contrast to the much lighter isotopic composition of inorganic mineral CaCO₃ (δ¹³C = −19.2‰; δ¹⁸O = −26.3‰). The differences indicated above were determined through principal component analysis, where the first and second principal components are sufficient for the clear distinction and traceability of CaCO₃ sources.

N. A. Salnikova, Yu. V. Shur, A. A. Tsibizova

Introduction. Currently, close attention in the field of pharmacy and medicine is directed to the search for new sources of biologically active substances of various origins, including vegetable. The woody plant Elaeagnus argentea is considered as a promising source. Despite its widespread use in the food industry, folk medicine as an anti-inflammatory, restorative, antimicrobial agent, the chemical composition of this plant has not been sufficiently studied.Aim. Qualitative and quantitative determination of the main groups of biologically active substances (BAS) in the raw material (leaves) of Elaeagnus argentea growing on the territory of the Astrakhan region for further development of a methodology for standardizing the raw material of this plant.Materials and methods. The leaves of Elaeagnus argentea were harvested in the spring in the eastern part of the delta of the Astrakhan region (Volga region). Drying of raw materials was carried out in natural conditions. In the study, unified methods were used: to determine the amount of flavonoids and saponins, the spectrophotometric method was used, ascorbic acid - the titrimetric method. For the analysis of flavonoids in the leaves of Elaeagnus argentea, an aqueous-alcoholic solution of 70 % concentration was used as an extractant. The quantitative content of flavonoids was determined in the obtained raw material extract in terms of luteolin-7-glucoside. The amount of saponins in the leaves of Elaeagnus argentea was determined in terms of oleanolic acid. 96 % ethanol was used as an extractant. The quantitative determination of ascorbic acid in the aqueous extract of crushed raw materials was carried out by titrimetry based on the ability to reduce 2,6-dichlorophenolindophenol.Results and discussion. In the pharmacognostic study of biologically active substances in the leaves of Elaeagnus argentea, the content of ascorbic acid was found to be at least 0.32 %, the amount of flavonoids in terms of luteolin-7-glucoside was at least 1.92 %; saponins - 2.38 %; which indicates the need for a more detailed study of the phytochemical composition of other morphological groups of the plant Elaeagnus argentea growing in the Astrakhan region.Conclusion. The data obtained during the study can be used to confirm the quality of raw materials (leaves) of Elaeagnus argentea. A more detailed study of leaves for the presence of other groups of biologically active substances will make it possible to use the obtained data for the development of regulatory documents for medicinal plant raw materials «Elaeagnus argentea leaves».