Natural and Synthetic Pharmaceutical Ingredients: Physico-Chemical Characterization and Drug Development

In recent years, new sources of secondary metabolites (SMs) in medicinal plants have been identified, and the introduction of these plants into field conditions has been carried out to obtain chemically diverse standardized raw material (RM). An example is mountain arnica Arnica montana L., one of Europe’s endemic endangered medicinal plant species, commonly used in pharmacy, cosmetics, and medicine. Its inflorescences (Arnicae flos) are characterized by anti-inflammatory, antiradical, antioxidant, antibacterial, antifungal, and antitumor properties. The main goals of the present research included: (i) characterization of the chemical composition of the inflorescences of A. montana harvested in different development stages; and (ii) presentation of the role of the development stage and different extraction methods in the antitumor activity of extracts through analyses of apoptosis, autophagy, and necrosis induction in human cervical carcinoma HeLa, human colon carcinoma HT29, and human colon metastatic carcinoma SW620 cell lines. The development stage was found to modify the composition of pharmacologically active substances, e.g., sesquiterpene lactones (SLs), flavonoids (Fs), and essential oil (EO), in arnica inflorescences. The content of Fs and EO increased during flowering to the full flowering phase; however, the highest content of SLs was noted in the full flowering phase and at the end of flowering. More promising results, i.e., a relatively high level of apoptosis and a low level of necrosis induced by the arnica extracts, were demonstrated in the HeLa cell line (full flowering; concentration: 0.5 µL/mL), the HT29 cell line (beginning of flowering; concentration: 0.5 µL/mL), and the SW620 cell line (stage of yellow buds; concentration: 1 µL/mL). This extremely valuable medicinal plant species provides a very broad range of RMs (e.g., inflorescences, rhizomes, roots, achenes, and all plant); therefore, attention should be paid to the more frequent use of water as a solvent in studies on the biological activity of mountain arnica extracts. Full article

The objective of this study was to develop microspheres (Ms) from natural materials, chitosan (Ch) and sodium alginate (Na-Alg), that protect Ruta graveolens L. (RG) extract against temperature, pH, and the oxidative impact of degradation. The microspheres also masked the unpleasant taste by enclosing them in a biodegradable polymeric matrix. First, the total polyphenols, total flavonoid content, and antioxidant activity were quantified spectrophotometrically. Individual polyphenol contents were identified and quantified by high-performance liquid chromatography (HPLC) with UV detection. The RG extract was encapsulated in microspheres of chitosan–sodium alginate–Ruta graveolens L. extract (CARG-Ms) using two distinct procedures (method 1, in which the RG extract was added to the Ch solution and the Na-Alg solution was dripped into this mixture, and method 2, in which the RG extract was added to the Na-Alg solution and then dripped into the Ch solution) to determine which method was more advantageous. All microspheres were evaluated and characterized by confocal laser-scanning microscopy (CLSM), scanning electron microscopy (SEM), optical scanning, entrapping efficiency (EE%), swelling index (SWL%), and in vitro release (RGrel%), and all results underwent univariate and multivariate analysis using a regression model. Following these tests, it was observed that the extract had an appreciable flavonoid content of 37.98%, with antioxidant properties evidenced by the 54.25% inhibition of DPPH. Of the polyphenolic compounds identified in the extract by using the HPLC method, rutin was present in the highest amount, at 745.17 μg/mL. The microspheres prepared by method 2, which contained the highest concentration of chitosan, had several desirable properties, including a high degree of roughness, high entrapping efficiency (75%), a wrinkled appearance, a better in vitro release capacity, and a lower SWL%. On the other hand, CARG-Ms prepared by method 1, which contained a smaller concentration of Ch, had faster swelling and slower release of the extract due to the lower entrapping efficiency (35%). These results suggest that the concentration of wall material and the preparation method play important roles in the encapsulation process and final particle characteristics. According to the obtained results, after the multivariate statistical analysis, it can be observed that the microspheres prepared via method 2 of the complex coacervation process were the most efficient for encapsulating rue extract in microspheres, because the extract was protected against degradation from the gastrointestinal tract. Full article

Natural products are promising drug candidates with various pharmacological effects. However, they can be difficult to use due to poor bioavailability or low stability. In this experiment, while developing topical formulations containing 0.1% Agrimonia pilosa extract, a simple and rapid method of analyzing flavonoid glucuronides, which are representative ingredients, was developed and validated, and the physicochemical properties and stability of flavonoid glucuronides were observed. As a result, an optimized cream formulation was developed. The oil phase comprised tween 60, liquid paraffin, propylene glycol, cetanol, stearyl alcohol, span 60, benzyl alcohol, and A. pilosa extracts, and the water phase comprised water and citric acid hydrate. Then, physicochemical and microbial stability tests of the formulation were conducted under long-term (12 months) and accelerated conditions (6 months). It was thus confirmed that both physicochemical and biological properties were stable during the test period. Consequently, an optimized formulation for the extract was developed and stability was confirmed. Full article

Individualised medicine demands the formulation of pharmacotherapy in accordance with the characteristics of each patient’s health condition, and paediatrics is one of the areas that needs this approach. The 3D printing of oral doses is one method for achieving customised medicine in paediatrics. In this work, pre-formulation studies were conducted to evaluate the viability of using specific raw materials to produce 3D printed dosage forms based on two active pharmaceutical ingredients (APIs), ondansetron and esomeprazole, which are important for therapeutic customisation in paediatrics. Pre-formulation studies were carried out by characterising the physical and chemical properties of selected raw materials, selected APIs and their mixtures, using analytical methods such as scanning electron microscopy (SEM), X-ray powder diffraction (X-RPD), simultaneous thermal analysis (STA) and differential scanning calorimetry (DSC). The flowability of powders, compatibility and stability studies were also performed. Among all the ingredients selected, the PVPs (K17, K25 and K90) had the best characteristics to incorporate both forms of Esomeprazole Mg in a formulation to produce extrudates. The results obtained validated the use of some selected raw materials for tablet manufacture by the 3D printing approach. Full article

Honey and other bee products have been used for food and therapeutic purposes since ancient times. There are many varieties of honey with time-proven therapeutic properties, used in both traditional and modern medicine, along with various beekeeping products. In this study, conducted based on the dissemination of a questionnaire with 43 questions, an evaluation of the consumption of different types of honey for both food and therapeutic purposes was carried out. Hence, the frequency of the consumption of honey for food purposes was evaluated, as well as the pharmaceutical forms of honey and bee products utilized for therapeutic purposes, the population’s trust in their therapeutic potential, and their trust in the quality of bee products among the Romanian population. After processing the data, 917 responses were recorded, and it was found that the preferred types of honey were black locust (83.5%), multi-floral (81.9%), and linden (74.9%), and among the other bee products, the most consumed were propolis (44.2%) and bee pollen (29.2%). Regarding the use of honey as a sweetener, the majority of the respondents considered honey to be the healthiest option (81.7%), and regarding the use of honey for therapeutic purposes, most of the respondents stated that they used honey to strengthen the immune system (65.4%), as well as for skin treatment, laxative action, or energizing. The centralization and processing of the collected responses indicated a considerable level of readiness related to the increase in honey consumption in particular, but there is a need for the dissemination of effective information related to the nutritional and therapeutic value of beekeeping products to the population. Full article

Herein, new extended-release tablets containing felodipine were developed. For the orally administered formulations, optimization of the preformulation and formulation parameters was performed to assess the performance of the dosage form. Initially, the morphological and physical characterization of two forms of felodipine (microcrystalline and macrocrystalline) using Fourier transform infrared spectroscopy, differential scanning calorimetry and optical microscopy was performed. The pharmaco-technical properties of the two felodipine forms were also determined. Subsequently, formulation studies for felodipine extended-release tablets were performed. Mathematical modelling of release kinetics of felodipine from developed formulations using a power law model was also performed. Based on the influence of formulation factors on the in vitro availability of felodipine in experimental tablets, a new extended-release tablet formulation was established. Full article