Oral Wound Healing Potential of Polygoni Cuspidati Rhizoma et Radix Decoction-In Vitro Study.

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.

Screening of Fenofibrate-Simvastatin Solid Dispersions in the Development of Fixed-Dose Formulations for the Treatment of Lipid Disorders.

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.

Hierarchical Macro-Mesoporous Silica Monolithic Tablets as a Novel Dose-Structure-Dependent Delivery System for the Release of Confined Dexketoprofen.

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.

Preformulation Studies of Ezetimibe-Simvastatin Solid Dispersions in the Development of Fixed-Dose Combinations.

Two active pharmaceutical ingredients (APIs) with limited solubility, simvastatin and ezetimibe, prepared as a drug-drug solid dispersion (SD) was evaluated for physicochemical, microstructural, and aqueous dissolution properties. The simvastatin-ezetimibe SD was prepared using the co-grinding method in a wide range of weight fractions and differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) were used to perform the phase composition analysis. DSC studies confirmed that simvastatin and ezetimibe form a simple eutectic phase equilibrium diagram. Analysis of Fourier transform infrared spectroscopy (FTIR) studies excluded strong interactions between the APIs. Our investigations have revealed that all studied dispersions are characterized by substantially improved ezetimibe dissolution regardless of simvastatin content, and are best when the composition oscillates near the eutectic point. Data obtained in our studies provide an opportunity for the development of well-formulated, ezetimibe-simvastatin fixed-dose combinations (for hypercholesterolemia treatment) with reduced ezetimibe dosages based on its dissolution improvement.

Binder jetting 3D printing of challenging medicines: From low dose tablets to hydrophobic molecules.

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.

Evaluation of the Influence of a Hydrogel Containing AMPD on the Stability of Tetracycline Hydrochloride.

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.

Pectin and Neutral Monosaccharides Production during the Simultaneous Hydrothermal Extraction of Waste Biomass from Refining of Sugar-Optimization with the Use of Doehlert Design.

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-1 ± 0.47 g kg-1) at a temperature and time of about 118.1 °C and 21.5 min, respectively. The highest yield of the sum of neutral monosaccharides (approx. 82.6 g kg-1 ± 0.72 g kg-1) was obtained at about 116.2 °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.