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This study reports the application of hierarchical porous monoliths as carriers for controlled and dose-adjustable release of model pharmaceutical (dexketoprofen, DEX). The synthesis and detailed characterization of the hierarchical porous scaffolds are provided before and after the adsorption of three doses of DEX─a widely used nonsteroidal anti-inflammatory drug. The drug incorporated in the mesopores of silica was stabilized in an amorphous state, while the presence of macropores provided sufficient space for drug crystallization as we demonstrated via a combination of powder X-ray diffraction, differential scanning calorimetry, and imaging techniques (scanning electron microscopy and EDX analysis). Drug release from silica matrices was tested, and a mechanistic model of this release based on the Fick diffusion equation was proposed. The hierarchical structure of the carrier, due to the presence of micrometric macropores and nanometric mesopores, turned out to be critical for the control of the drug phase and drug release from the monoliths. It was found that at low drug content, the presence of an amorphous component in the pores promoted the rapid release of the drug, while at higher drug contents, the presence of macropores favored the crystallization of DEX, which naturally slowed down its release. Both the hierarchical porous structure and the control of the drug phase (amorphous and/or crystalline) were proven important for adjustable (fast or prolonged) release kinetics, desirable for effective pharmacotherapy and patient compliance. Therefore, the developed materials may serve as a versatile formulation platform for the smart manipulation of drug release kinetics.

In this work one-stage, no presence of acidic catalyst hydrothermal extraction of pectin from sugar beet pulp (SBP) as a batch process was investigated, leading to increasing the value of this by-product of sugar beet industry. The comprehensive study of the effect of the extraction temperature and the extraction time on the yield and composition of the pectin-enriched products, the water soluble product fractions and the water insoluble product fractions, were used that are feasible for industrial upscaling. It was shown that the highest yield of satisfactory purity of pectin extract (136.3 g kg−1) was obtained at a temperature of 120 °C and a holding time of 20 min. Both further increase of the extraction temperature and extending extraction time favor the occurrence of partial hydrothermolysis of pectin and hemicellulose contained in the SBP, leading to the production of uronic acids, monosaccharides, carboxylic acids and furfurals. In the applied extraction conditions, other components of the SBP: cellulose, lignin and protein did not undergo depolymerization and were still present in the solid post-extraction residue. This work provides an important method for the recovery of pectin from SBP using environmentally friendly technique and should help to facilitate further studies to develop a new process for the hydrothermal production of pectin from waste biomass.

The objective of this work was to investigate binary pharmaceutical mixtures of ezetimibe (EZT) and aspirin (ASA) in order to identify whether the occurrence of eutectic in this system has an effect on EZT dissolution improvement. Ezetimibe–aspirin (EZT–ASA) solid dispersions prepared by grinding in the whole range of compositions were characterized using differential scanning calorimetry (DSC) for purpose to describe solid-liquid phase equilibrium diagram. The occurrence of interactions between ingredients was excluded by Fourier transform infrared spectroscopy and X-ray powder diffractometry. Dissolution studies have shown that the mixtures containing from 10 to 60 mass% of EZT (53.5 mass% of EZT in eutectic composition) have released ezetimibe faster than a sample of pure drug. Moreover, ASA is released more quickly from all obtained dispersions than from powder alone. Our studies have shown that obtained mixtures are useful to obtain the fixed-dose combinations, capable to deliver these two APIs together in a single system with enhanced dissolution of EZT and ASA.

Background Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders, characterized by the presence of various symptoms related to deficits in communication and social interactions as well as stereotyped and repetitive behavior. Increasing evidence indicates the contribution of genetic factors in the etiology of ASDs. Genetic diagnosis in ASDs is based on identifying chromosome aberrations, microaberrations and point mutations in specific genes. One of the diagnostic tools is multiplex ligase-dependent probe amplification (MLPA) with a set of probes dedicated to ASDs (SALSA MLPA P343 Autism-1; MRC-Holland BV, Amsterdam, the Netherlands) targeting the genes located in the regions 15q11-q13, 16p11 and the SHANK3 gene in the 22q13 region. Objectives Our study included 240 patients referred to the clinical genetics unit because of ASDs and/or developmental delay and/or an intellectual disability. Before genetic testing, the patients underwent a comprehensive medical work-up. Material and methods Multiplex ligase-dependent probe amplification was performed in 256 DNA samples from 240 probands and 16 family members using the SALSA MLPA P343 Autism-1 probe mix (MRC-Holland BV) according to the manufacturer's protocol. Results We obtained 234 normal results and 22 abnormal results (15 probands and 7 abnormal results for probands' parents or siblings). We diagnosed 1 16p11 microdeletion syndrome and 1 16p11 microduplication syndrome. We also found 3 deletions and 1 duplication in 15q13 region including 2 or 3 genes and 9 single probe alterations in the regions examined (1 duplication and 7 deletions). Conclusions Due to the low costs, MLPA test may be a good tool for the genetic screening of ASD patients.

The citrus peel contains hesperidin, a flavonoid with a wide range of biological activities. Recent scientific literature discusses the extraordinary versatility of hesperidin, which is reflected in its antioxidant, anti-inflammatory, cardio- protective and antidiabetic properties. However, hesperidin is quite unstable and therefore should be encapsulated to protect its bioactivity from the effects of environmental conditions. Among the other popular microencapsulation techniques, spray drying allows rapid evaporation of water and maintains a relatively low temperature within the particles. In this study, citrus peel extracts were spray-dried using gum Arabic and maltodextrin as encapsulating agents at the temperature of 120 °C and a flow rate of 4 mL/min. Citrus peel extracts were produced by ultrasonic-assisted extraction with 70% ethanol as a solvent, while the determination of hesperidin was performed using high-performance liquid chromatography. The hesperidin retention in the microcapsules was 461.03 and 433.76 mg/g for microcapsules encapsulated with maltodextrin and gum Arabic, respectively. However, higher encapsulation efficiency (difference between surface and total hesperidin content) was achieved when maltodextrin was used as an encapsulating agent. Citrus peel showed as a possible alternative to commercial hesperidin sources, while spray drying showed as a reliable and effective tool for its encapsulation.

Polygoni Cuspidati Rhizoma et Radix (syn. rhizomes of Reynoutria japonica Houtt.) is a pharmacopoeial raw material in Europe and China. In traditional medicine, one of the applications for Reynoutria japonica rhizomes is wound healing. In a recent in vitro study, we demonstrated that ethanol and acetone extracts from this herbal drug have the potential to heal oral gum wounds. However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope—CLSM), and cell migration (wound healing assay). Moreover, the collagen type III expression was examined using immunocytochemical staining. The studied decoction was qualitatively and quantitatively characterized using the validated HPLC/DAD/ESI-HR-QTOF-MS method. The Folin–Ciocalteu assay was used to determine the total phenols and tannins content. Additionally, HPLC-RI analysis of decoction and the previously obtained ethanol and acetone extracts was used to determine the composition of saccharides. Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation caused a significant increase in HGF cell viability. No cytotoxic effect was observed at any tested concentration (up to 2000 µg/mL). The lowest active concentration of decoction (50 µg/mL) was selected for further experiments. It significantly stimulated human gingival fibroblasts to proliferate, migrate, and increase the synthesis of collagen III. Phytochemical analysis showed significantly fewer polyphenols in the decoction than in the ethanol and acetone extracts tested earlier. In contrast, high levels of polysaccharides were observed. In our opinion, they may have a significant effect on the oral wound healing parameters analyzed in vitro. The results obtained encourage the use of this raw material in its traditional, safe form—decoction.

The combination of statins and fibrates in the treatment of lipid abnormalities effectively regulates individual lipid fraction levels. In this study, the screening and assessment of the physicochemical properties of simvastatin-fenofibrate solid dispersions were performed. Fenofibrate and simvastatin were processed using the kneading method in different weight ratios, and the resulting solid dispersions were assessed using differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), contact angle, as well as dissolution tests. The obtained results confirmed the formation of a simple eutectic phase diagram, with a eutectic point containing 79 wt% fenofibrate and 21 wt% simvastatin, lack of chemical interactions between the ingredients, and simvastatin impact on improving fenofibrate dissolution profile, due to the formation of crystalline solid dispersions by the kneading method.

Increasing access to additive manufacturing technologies utilising easily available desktop devices opened novel ways for formulation of personalized medicines. It is, however, challenging to propose a flexible and robust formulation platform which can be used for fabrication of tailored solid dosage forms composed of APIs with different properties (e.g., hydrophobicity) without extensive optimization. This manuscript presents a strategy for formulation of fast dissolving tablets using binder jetting (BJ) technology. The approach is demonstrated using two model APIs: hydrophilic quinapril hydrochloride (QHCl, logP = 1.4) and hydrophobic clotrimazole (CLO, logP = 5.4). The proposed printing method uses inexpensive well known and easily available FDA approved pharmaceutical excipients. The obtained model tablets had uniform content of the drug, excellent mechanical properties and highly porous structure resulting in short disintegration time and fast dissolution rate. The tablets could be scaled and obtained in predesigned shapes and sizes. The proposed method may find its application in the early stages of drug development where high flexibility of the formulation is required and the amount of available API is limited.

Tetracyclines, as beneficial antimicrobial factors in both local and systemic therapy, are characterized by high instability. The aim of the study was the development of the influence of hydrogel formulation on the tetracycline hydrochloride (TC) level under varying storage conditions. The HPLC, XPRD as well as SEM and macroscopic observations were involved in the study. The TC concentration decreased within ca. two months from 9.37 µg/mL to 4.41 µg/mL in the case of the photoprotected TC solution stored at 23 °C, whereas the decrease in storage temperature did not improve the final level of TC. In the presence of AMPD, the TC level in aqueous solution decreased drastically to ca. 1 µg/mL. Application of a polyacrylic acid derivative enabled conservation of the TC level through the ca. two months. Thus, the use of alcoholamine in the preparation of the TC hydrogel may result in the development of a therapeutic product with a dual action against acne, including antimicrobial activity and saponification of free fatty acids deposited in the follicles.

The hydrolysis of high methyl ester citrus-apple pectin as a model substance for plant biomass waste rich in pectin fraction resulting in an uronic acids was performed in a batch reactor using subcritical water. The effects of the reaction temperature and time on the composition of the products contained in the separated liquid fractions were studied. The optimal experimental design methodology was used for modelling and optimizing the yield of uronic acids. In good agreement with experimental results (R2 = 0.986), the model predicts an optimal yield of uronic acids (approx. 77.3 g kg-1 ± 0.7 g kg-1) at a temperature and a time of about 155°C and 36 min. Uronic acids were isolated from reaction mixture using the ion exchange method. Higher temperature and longer holding time resulted in a greater degree of thermal degradation of uronic acids and simultaneously higher yield of losses and gas fractions

We propose a one-stage hydrothermal extraction of sugar beet pulp leading to effective co-production of pectin and neutral monosaccharides with a relatively high yield and satisfactory purity without the presence of an acidic catalyst. The optimal experimental design methodology was used for modelling and optimizing the yield of pectin and neutral monosaccharides. In good agreement with experimental results (R2 = 0.955), the model predicts an optimal yield of pectin (approx. 121.1 g kg&minus, 1 &plusmn, 0.47 g kg&minus, 1) at a temperature and time of about 118.1 &deg, C and 21.5 min, respectively. The highest yield of the sum of neutral monosaccharides (approx. 82.6 g kg&minus, 0.72 g kg&minus, 1) was obtained at about 116.2 &deg, C and 26.4 min (R2 = 0.976). The obtained results are suitable for industrial upscaling and may provide an incentive to implement a new, environmentally friendly, simple, and effective method for treating waste product from the sugar refining industry, which has proved onerous until now.

Alkali lignin as an example of waste plant biomass was subjected in a batch reactor to decomposition in sub- and supercritical water. Hydrothermolysis of alkali lignin with relatively highmolecular-weight led to the production of phenolic compounds such as guaiacol and catechol, as well as phenol, m -cresol, p -cresols and o -cresol. Both an increase growth in conversion time and an increase in reaction temperature promoted secondary reactions: degradation of alkali lignin decomposition products, leading to, their repolymerization and carbonization. The components of the liquid fractions of products were examined by GC–MS and HPLC, whereas the solid charred post-reaction residues were analyzed by elemental analysis and FTIR.