Development and Comprehensive Characteristics of Thermosensitive Liquid Suppositories of Metoprolol Based on Poly(lactide-co-glycolide) Nanoparticles.

Thermosensitive liquid suppositories (LSs) carrying the model antihypertensive drug metoprolol tartrate (MT) were developed and evaluated. The fundamental purpose of this work was to produce, for the first time, liquid MT suppositories based on biodegradable nanoparticles and optimize their rheological and mechanical properties for prospective rectal administration. The nanoparticle system was based on a biodegradable copolymer synthesized by ring opening polymerization (ROP) of glycolide (GL) and L,L-lactide (LLA). Biodegradable nanoparticles loaded with the model drug were produced by the o/o method at the first stage of the investigation. Depending on the concentration of the drug in the sample, from 66 to 91% of MT was released over 12 h, according to first-order kinetics. Then, thermosensitive LSs with MT-loaded biodegradable nanoparticles were obtained by a cold method and their mechanical and rheological properties were evaluated. To adjust the thermogelling and mucoadhesive properties for rectal administration, the amounts of major formulation components such as poloxamers (P407, P188), Tween 80, hydroxypropylcellulose (HPC), polyvinylpyrrolidone (PVP), and sodium alginate were optimized. The in vitro release results revealed that more than 80% of the MT was released after 12 h, following also first-order kinetics. It was discovered that the diffusion process was dominant. The drug release profile was mainly governed by the rheological and mechanical properties of the developed formulation. Such a novel, thermosensitive formulation might be an effective alternative to hypertension treatment, particularly for unconscious patients, patients with mental illnesses, geriatric patients, and children.

Achievements in Thermosensitive Gelling Systems for Rectal Administration.

Rectal drug delivery is an effective alternative to oral and parenteral treatments. This route allows for both local and systemic drug therapy. Traditional rectal dosage formulations have historically been used for localised treatments, including laxatives, hemorrhoid therapy and antipyretics. However, this form of drug dosage often feels alien and uncomfortable to a patient, encouraging refusal. The limitations of conventional solid suppositories can be overcome by creating a thermosensitive liquid suppository. Unfortunately, there are currently only a few studies describing their use in therapy. However, recent trends indicate an increase in the development of this modern therapeutic system. This review introduces a novel rectal drug delivery system with the goal of summarising recent developments in thermosensitive liquid suppositories for analgesic, anticancer, antiemetic, antihypertensive, psychiatric, antiallergic, anaesthetic, antimalarial drugs and insulin. The report also presents the impact of various types of components and their concentration on the properties of this rectal dosage form. Further research into such formulations is certainly needed in order to meet the high demand for modern, efficient rectal gelling systems. Continued research and development in this field would undoubtedly further reveal the hidden potential of rectal drug delivery systems.

Determination of the elemental composition and antioxidant properties of dates (Phoenix dactyliferia) originated from different regions.

Due to the growing interest in running a healthy life, including the diet a special interest has been put in searching for products that are rich in nutrients, macro and micronutrients and vitamins. Dates are the fruits that meet these requirements and show multidirectional pro-health effects. These fruits are a source of potassium and other macro- and micronutrients. They have antioxidant properties thanks to the content of flavonoids and polyphenols. The elemental composition (Al, Ca, Cu, Fe, K, Mg, Mn, P, Sr and Zn) and antioxidant properties (total equivalent antioxidant capacity, total polyphenol content, total flavonoid content) of various dates from different regions of the world was determined. The results have shown that the peel and flesh of dates differ significantly in chemical composition. The peel is significantly richer in chemical components of biological importance. Discriminant analysis of the results obtained for dates originated from various regions indicated that the main factor determining the tested chemical composition is the place of cultivation, not the variety.

Biodegradable synthetic polyesters in the technology of controlled dosage forms of antihypertensive drugs - the overview.

Introduction: Arterial hypertension is a disease of civilization that requires long-term treatment. Recently, growing interest in natural and synthetic polymers as drug delivery vehicles in controlled release dosage forms for improving the efficacy of treatment has been observed. Areas covered: This review introduces biodegradable synthetic polyesters as macromolecular carriers of antihypertensive drugs. Although various, synthetic and natural polymer-drug conjugates and/or polymeric carriers of anticancer drugs are currently under preclinical and clinical studies, there is no such data for antihypertensive drugs. Therefore, it seems appropriate to use such materials for the treatment of hypertension. Expert opinion: There are currently only a few studies describing the use of synthetic polyesters in the arterial hypertension therapy. In order to the fact that there is a high demand for new, effective antihypertensive dosage forms, further studies for such drug carriers are certainly expected. Synthetic polyester carriers could improve the drug bioavailability and its pharmacokinetic properties by altering the pharmaceutical dosage form. This property is particularly useful for drugs with proven pharmacological action, but with limited application due to their inappropriate pharmacological properties. The development of new polymeric materials and technologies affords the opportunity to produce novel synthetic polyester DDSs.

Effect of carbonate substitution on physicochemical and biological properties of silver containing hydroxyapatites.

Ag+-substituted hydroxyapatites (Ag-HAs) and Ag+/CO32--co-substituted hydroxyapatites (Ag-CHAs) with two different concentrations of silver ions were synthesized by the standard precipitation method. For comparison, pure hydroxyapatite (HA) and carbonated hydroxyapatite (CHA) were synthesized using the same method. The obtained powders were examined by various physicochemical methods, such PXRD, TEM, FTIR and ssNMR. Elemental analysis was provided by WD-XRF and ICP-MS methods. The strains of Staphylococcus aureus and Escherichia coli were used to evaluate the antibacterial activity of the materials. The study demonstrates that the substituted samples are homogenous and poorly crystalline. Introducing carbonates into the crystal structure significantly affects the physicochemical properties of the silver containing hydroxyapatite, i.e., crystallinity, lattice parameters, crystal size and morphology or content of structural hydroxyl groups. Carbonate substitution leads to a significant increase in the contribution of the hydrated surface layer. Ag-CHA nanocrystals with an enhanced hydrated surface layer and higher solubility demonstrate an admirable antibacterial effect.

Biodegradable Poly(ester-urethane) Carriers Exhibiting Controlled Release of Epirubicin.

PURPOSE: The purpose of this study was to develop the perspective biodegradable poly(ester-urethane) (PUR) carriers based on "predominantly isotactic" and atactic polylactides (PLAs), and poly(ε-caprolactone) (PCL), for the controlled release of epirubicin (EPI). METHODS: The biodegradable PURs containing different soft segments as new and effective carriers of EPI have been obtained. The preliminary studies on toxicity and degradation of obtained polymers, and the release of the EPI from PUR carriers were carried out. RESULTS: We found that the kinetic release of EPI from the obtained PUR carriers tested in vitro at 37°C and pH 7.4 was strongly dependent on the kind of the polyesters, used as the soft segment in PURs synthesis. Furthermore, we demonstrated that the EPI was released from various synthesized carriers in a rather regular manner, according to the diffusion-degradation and degradation mechanisms. Importantly, in some cases, the kinetics of the EPI release was nearly zero-order. CONCLUSION: The results show that the obtained PURs are very effective and perspective carriers and might be potentially applied in the technology of high controlled EPI delivery systems.

A solid-state NMR study of selenium substitution into nanocrystalline hydroxyapatite.

The substitution of selenium oxyanions in the hydroxyapatite structure was examined using multinuclear solid-state resonance spectroscopy (ssNMR). The study was supported by powder X-ray diffractometry (PXRD) and wavelength dispersion X-ray fluorescence (WD-XRF). Samples of pure hydroxyapatite (HA300) and selenate (HA300-1.2SeO4) or selenite (HA300-1.2SeO3) substituted hydroxyapatites were synthesized using the standard wet method and heated at 300 °C to remove loosely bonded water. PXRD data showed that all samples are single-phase, nanocrystalline hydroxyapatite. The incorporation of selenite and selenate ions affected the lattice constants. In selenium-containing samples the concentration of Se was very similar and amounted to 9.55% and 9.64%, for HA300-1.2SeO4 and HA300-1.2SeO3, respectively. PXRD and ssNMR data showed that the selenite doping significantly decreases the crystallite size and crystallinity degree. 31P and 1H NMR experiments demonstrated the developed surface hydrated layer in all samples, especially in HA300-1.2SeO3. 1H NMR studies showed the dehydroxylation of HA during the selenium oxyanions substitution and the existence of hydrogen bonding in structural hydroxyl group channels. 1H→77Se cross polarization NMR experiments indicated that selenites and selenates are located in the crystal lattice and on the crystal surface.

Cannabis profiling based on its elemental composition--is it possible?

Elemental composition of 85 cannabis samples was established using GF AAS and ICP OES methods. The robustness of the method was determined by analyzing eight independently prepared replicates from a single cannabis plant. The accuracy of the method was established by analyzing four plant certified reference material samples. The ability of discriminant analysis using elemental compositions to distinguish between fiber cannabis samples collected from four different regions of Poland was evaluated. Then, a classification model was developed that correctly classified selected samples of known origin. Cannabis samples confiscated by law enforcement agencies have also been subjected to discriminant analysis. A classification model has been developed for four locations in Poland (Bialystok, Koscierzyna, the environs of Skarzysko Kamienna, and Bydgoszcz), to help determine where samples of unknown origin could have been grown.

Kinetics of 1H→13C NMR cross-polarization in polymorphs and solvates of the antipsychotic drug olanzapine.

The (1)H→(13)C NMR cross-polarization (CP) was studied under magic-angle spinning at 7.5 kHz in various crystal forms of the antipsychotic drug olanzapine: two polymorphs (metastable I and stable II) and eight solvates containing organic solvent and water molecules. The CP kinetics followed the non-classical I-I(*)-S model, in which CP begins in a spin cluster of proximate abundant spins I(*) and rare spins S, then is controlled by spin diffusion of the abundant spins I from bulk to the I(*) spins of the spin cluster and finally is governed by spin-lattice relaxation of the abundant spins in the rotating frame. The corresponding CP kinetics parameters were determined and analyzed. It was demonstrated that the, λ and T(df) values (the CP time constant, the cluster composition parameter and the (1)H spin-diffusion constant, respectively) were very useful to discriminate the functional groups, especially in the 3D parameter space. In order to conveniently analyze the large amount (175) of the collected CP parameters, the number of the observed variables was reduced using the principal component (PC) analysis. The 2D plot of PC2 vs. PC1 showed adequate separation of the CH(3), CH(2), CH and C cases (C stands for carbons without adjacent hydrogens). It was demonstrated that those cases were located along the PC1 axis in the order of increasing (1)H-(13)C dipolar couplings: C