Synthesis and Characterization of Nanoporous Carbon Carriers for Losartan Potassium Delivery.

Losartan potassium is most commonly used for the treatment of hypertension. In recent years, new applications of this drug have emerged, encouraging the design of novel nanoporous carriers for its adsorption and release. The purpose of this study was to synthesize ordered mesoporous carbon vehicles via a soft-templating method altered with the use of nitrogen precursors and via a hard-templating method followed by chitosan functionalization. As a result, the materials obtained differed in nitrogen content as well as in the number of total surface functional groups. The impact of the modification on the physicochemical properties of carbon carriers and their interaction with losartan potassium during adsorption and release processes was examined. The materials were characterized by various morphologies, specific surface areas (101-1180 m2 g-1), and the amount of acidic/basic oxygen-containing functional groups (1.26-4.27 mmol g-1). These features, along with pore sizes and volumes, had a key effect on the sorption capacity of carbon carriers towards losartan potassium (59-161 mg g-1). Moreover, they contributed to the differential release of the drug (18.56-90.46%). Losartan potassium adsorption onto the surface of carbonaceous materials was mainly based on the formation of hydrogen bonds and π-π interactions and followed the Langmuir type isotherm. It has been shown that the choice of the method of carbon carriers' synthesis and their modification allows for the precise control of the kinetics of the losartan potassium release from their surface, resulting in rapid or sustained drug liberation.

Analysis of the Composition of Lyophilisates Obtained from Aloe arborescens Gel of Leaves of Different Ages from Controlled Crops.

The aim of the study is to evaluate the composition of lyophilisates obtained from Aloe arborescens leaf gel at the age of one to four years. The leaves were obtained from controlled crops, which allowed to exclude environmental factors as variables. It was confirmed that the lyophilisates obtained from different years of Aloe arborescens leaf gel varied in chromatographic analyses in terms of aloin A and aloenin A content (high-performance liquid chromatography with diode-array detection HPLC-DAD, high-performance liquid chromatography with tandem mass spectrometric detection HPLC-MS/MS). Similarly, while testing the phenolic acids and the sum of polyphenols content, differences in their levels in leaf gel lyophilisates from plants of individual years were observed (spectrophotometric method UV-VIS). The lyophilisate composition analysis showed that the one-year-old leaves were characterized by the highest content of aloin A and aloenin A. While the content of polyphenols, including phenolic acids, was higher in the leaves of older plants. The antioxidant potential of the tested lyophilisates was assessed simultaneously. Regardless of the research model used (CUPRAC, DPPH, ABTS), an antioxidant effect was noted for Aloe arborescens leaves.

Combinations of Freeze-Dried Amorphous Vardenafil Hydrochloride with Saccharides as a Way to Enhance Dissolution Rate and Permeability.

To improve physicochemical properties of vardenafil hydrochloride (VAR), its amorphous form and combinations with excipients-hydroxypropyl methylcellulose (HPMC) and ß-cyclodextrin (ß-CD)-were prepared. The impact of the modification on physicochemical properties was estimated by comparing amorphous mixtures of VAR to their crystalline form. The amorphous form of VAR was obtained as a result of the freeze-drying process. Confirmation of the identity of the amorphous dispersion of VAR was obtained through the use of comprehensive analysis techniques-X-ray powder diffraction (PXRD) and differential scanning calorimetry (DSC), supported by FT-IR (Fourier-transform infrared spectroscopy) coupled with density functional theory (DFT) calculations. The amorphous mixtures of VAR increased its apparent solubility compared to the crystalline form. Moreover, a nearly 1.3-fold increase of amorphous VAR permeability through membranes simulating gastrointestinal epithelium as a consequence of the changes of apparent solubility (Papp crystalline VAR = 6.83 × 10-6 cm/s vs. Papp amorphous VAR = 8.75 × 10-6 cm/s) was observed, especially for its combinations with ß-CD in the ratio of 1:5-more than 1.5-fold increase (Papp amorphous VAR = 8.75 × 10-6 cm/s vs. Papp amorphous VAR:ß-CD 1:5 = 13.43 × 10-6 cm/s). The stability of the amorphous VAR was confirmed for 7 months. The HPMC and ß-CD are effective modifiers of its apparent solubility and permeation through membranes simulating gastrointestinal epithelium, suggesting a possibility of a stronger pharmacological effect.

Amine-Grafted Mesoporous Carbons as Benzocaine-Delivery Platforms.

Smart porous carriers with defined structure and physicochemical properties are required for releasing the therapeutic drug with precise control of delivery time and location in the body. Due to their non-toxicity, ordered structure, and chemical and thermal stability, mesoporous carbons can be considered modern carriers for active pharmaceutical ingredients whose effectiveness needs frequent dosing algorithms. Here, the novel benzocaine delivery systems based on ordered mesoporous carbons of the cubic structure were obtained with the use of a hard template method and functionalization with amine groups at 40 °C for 8 h. It has been shown that amine grafting strongly modifies the surface chemistry and textural parameters of carbons. All samples indicated good sorption ability towards benzocaine, with evident improvement following the functionalization with the amine groups. The sorption capacity and drug release kinetics were strongly affected by the porosity of carbon carriers and the surface functional groups. The smallest amount of benzocaine (~12%) was released from pristine mesoporous carbon, which could be correlated with strong API-carrier interactions. Faster and more efficient release of the drug was observed in the case of triethylenetetramine modified carbon (~62%). All benzocaine delivery platforms based on amine-grafted mesoporous carbons revealed high permeability through the artificial membrane.

Design of Paracetamol Delivery Systems Based on Functionalized Ordered Mesoporous Carbons.

The oxidized ordered mesoporous carbons of cubic and hexagonal structure obtained by two templating methods (soft and hard) were applied for the first time as delivery systems for paracetamol-the most common antipyretic and analgesic drug in the world. The process of carbon oxidation was performed using an acidic ammonium persulfate solution at 60 °C for 6 h. The functionalization was found to reduce the specific surface area and pore volume of carbon materials, but it also led to an increasing number of acidic oxygen-containing functional groups. The most important element and the novelty of the presented study was the evaluation of adsorption and release ability of carbon carriers towards paracetamol. It was revealed that the sorption capacity and the drug release rate were mainly affected by the materials' textural parameters and the total amount of surface functional groups, notably different in pristine and oxidized samples. The adsorption of paracetamol on the surface of ordered mesoporous carbons occurred according to different mechanisms: donor-acceptor complexes and hydrogen bond formation. The adsorption kinetics was assessed using pseudo-first- and pseudo-second-order models. The regression results indicated that the adsorption kinetics was more accurately represented by the pseudo-second-order model. Paracetamol was adsorbed onto the carbon materials studied following the Langmuir type isotherm. The presence of oxygen-containing functional groups on the surface of ordered mesoporous carbons enhanced the amount of paracetamol adsorbed and its release rate. The optimal drug loading capacity and expected release pattern exhibited oxidized ordered mesoporous carbon with a hexagonal structure obtained by the hard template method.