Supercritical CO2-assisted processes for development of added-value materials: Optimization of starch aerogels preparation and hemp seed extracts impregnation

The aim of the present study was the utilization of supercritical CO2 as a green medium in various processes: starch gel drying, supercritical extraction from hemp seed flour (SCE process), hemp seed oil (HSO) impregnation (SCI process), as well as integrated process of hemp seed flour (HSF) extraction and starch gels impregnation (SCE-SCI process) for development of added-value materials that can be used as phytopharmaceuticals. Optimization of starch aerogels was performed by variation of temperature (35 and 45 °C) and pressure (8, 10, and 20 MPa) in order to obtain materials with high porosity, which will enable maximal loading capacity for hemp seed extracts. Proposed scCO2-assisted processes of SCE from HSF, SCI and SCE-SCI were performed at pressure of 30 MPa and temperature of 60 °C. It was shown that conditions of starch gel drying significantly influenced material morphology (porosity was in a range of 48-82%, and specific surface area of 71-208 m2/g), which consequently determined aerogel loading capacity. FTIR analysis confirmed that scCO2 did not have effect on polymer composition nor it remained in polymer after drying process. The highest loading of both HSO and HSF extract (24.9% and 29.78%, respectively) was achieved when aerogel obtained at 10 MPa and 45 °C was tested as a carrier. Furthermore, chemical analysis showed that both HSO and HSF extract are rich in unsaturated fatty acids especially linoleic acid (54-59%) and α-linolenic acid (15-18%). These essential fatty acids have well-established health benefits including protection against cardiovascular, neurodegenerative and inflammatory diseases

Comparative analyses of diffusion coefficients for different extraction processes from thyme

This work was aimed to analyze kinetics and mass transfer phenomena for different extraction processes from thyme (Thymus vulgaris L.) leaves. Different extraction processes with ethanol were studied: Soxhlet extraction and ultrasound-assisted batch extraction on the laboratory scale as well as pilot plant batch extraction with mixing. The extraction processes with ethanol were compared to the process of supercritical carbon dioxide extraction performed at 10 MPa and 40°C. Experimental data were analyzed by mathematical model derived from the Fick’s second law to determine and compare diffusion coefficients in the periods of constant and decreasing extraction rate. In the fast extraction period, values of diffusion coefficients were one to three orders of magnitude higher compared to those determined for the period of slow extraction. The highest diffusion coefficient was reported for the fast extraction period of supercritical fluid extraction. In the case of extraction processes with ethanol, ultrasound, stirring and extraction temperature increase enhanced mass transfer rate in the washing phase. On the other hand, ultrasound contributed the most to the increase of mass transfer rate in the period of slow extraction

Selection of the suitable polymer for supercritical fluid assisted preparation of carvedilol solid dispersions

Solid dispersions production is one of the substantial approaches for improvement of poor drug solubility. Additionally, supercritical fluid assisted method for preparation of solid dispersions can offer many advantages in comparison to the conventional melting or solvent-evaporation methods. Miscibility analysis provides valuable guidance for selection of the most appropriate polymeric carrier for dispersion of the drug of interest. In addition to the increased drug release rate, solid dispersions should have proper mechanical attributes in order to be successfully formulated in the final solid dosage form such as tablet. Therefore, several pharmaceutical grade polymers have been selected for development of BCS Class II drug carvedilol (CARV) solid dispersions. They were compared based on behavior in supercritical CO 2 and affinity towards CARV calculated from the miscibility analysis. By utilization of the supercritical CO 2 assisted method, solid dispersions of CARV with the selected (co)polymers (polyvinylpyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), Soluplus® and Eudragit®) were obtained. Properties of the prepared CARV-polymer dispersions were observed by the polarizing and scanning electron microscopy and analyzed by differential scanning calorimetry and Fourier transform infrared spectroscopy. CARV was additionally characterized by X-ray powder diffraction. Furthermore, in vitro dissolution studies and dynamic compaction analysis were performed on the selected samples of solid dispersions. Among the studied polymers, PVP and HPMC have been identified as polymers with the highest affinity towards CARV, based on the calculated δ p values. This has been also confirmed with the highest dissolution efficiency of CARV-PVP and CARV-HPMC solid dispersions. Solid state characterization indicated that CARV was dispersed either molecularly, or in the amorphous form, depending on interactions with each polymer. Determination of CARV-PVP and CARV-HPMC mechanical properties revealed that CARV-PVP solid dispersion has superior compactibility and tabletability. Therefore, CARV-PVP solid dispersion has been highlighted as the most appropriate for the further development of tablets as the final dosage form. Presented study provides an example for efficient approach for development of poorly soluble drug solid dispersion with satisfactory tableting properties.This is the peer-reviewed version of the following article: Đuriš, J., Milovanović, S., Medarević, Đ., Dobričić, V., Dapčević, A.,& Ibrić, S.. (2019). Selection of the suitable polymer for supercritical fluid assisted preparation of carvedilol solid dispersions. International Journal of Pharmaceutics Elsevier Science Bv, Amsterdam., 554, 190-200. [https://doi.org/10.1016/j.ijpharm.2018.11.015]Published version [http://technorep.tmf.bg.ac.rs/handle/123456789/4335

Dandelion seeds as a new and valuable source of bioactive extracts obtained using the supercritical fluid extraction technique

The present study was intended to explore dandelion seeds as a new source of biologically active constituents using an environmentally friendly extraction technique. The process-function relationships were determined by following the influence of temperature (40 and 60 °C) and pressure (from 100 to 450 bar) on the amount of separated extract, its density, composition, and bioactivity. It was shown that the supercritical CO2-assisted technique enables the separation of 0.6–25.0% extract having a density in a range of 827–941 kg/m3. Extracts contained a high amount of unsaturated fatty acids (89.9–90.6%) including linoleic acid (71%) and α-linolenic acid (up to 0.9%), as well as phenolic (5.5–12.1 mg GAE/g) and flavonoid compounds (208.6–564.5 μg QE/g). The antioxidant activity test showed that 20 mg/mL extract solutions inhibit 26.0–64.4% DPPH radical. In addition, extracts showed significant antimicrobial activity, especially against Gram-positive Bacillus subtilis and Micrococcus luteus. There was no cytotoxic effect on normal green monkey kidney cells and human skin fibroblasts nor on hypopharyngeal cancer, cervical adenocarcinoma, and colon cancer cells. The study indicated the possible safe application of bioactive dandelion seeds extract in the pharmaceutical, food, and cosmetic industry

Green Processing of Neat Poly(lactic acid) Using Carbon Dioxide under Elevated Pressure for Preparation of Advanced Materials: A Review (2012–2022)

This review provides a concise overview of up-to-date developments in the processing of neat poly(lactic acid) (PLA), improvement in its properties, and preparation of advanced materials using a green medium (CO2 under elevated pressure). Pressurized CO2 in the dense and supercritical state is a superior alternative medium to organic solvents, as it is easily available, fully recyclable, has easily tunable properties, and can be completely removed from the final material without post-processing steps. This review summarizes the state of the art on PLA drying, impregnation, foaming, and particle generation by the employment of dense and supercritical CO2 for the development of new materials. An analysis of the effect of processing methods on the final material properties was focused on neat PLA and PLA with an addition of natural bioactive components. It was demonstrated that CO2-assisted processes enable the control of PLA properties, reduce operating times, and require less energy compared to conventional ones. The described environmentally friendly processing techniques and the versatility of PLA were employed for the preparation of foams, aerogels, scaffolds, microparticles, and nanoparticles, as well as bioactive materials. These PLA-based materials can find application in tissue engineering, drug delivery, active food packaging, compostable packaging, wastewater treatment, or thermal insulation, among others

Application of cellulose acetate for controlled release of thymol

Cellulose acetate (CA) was investigated as a carrier towards development of material with controlled release of thymol as a natural substance with strong antibacterial properties using high pressure techniques. Effect of thymol content on CA was confirmed by SEM, FTIR and DSC methods. Kinetic of thymol release from CA was tested using simulated gastric and intestinal fluids (hydrochloric acid and phosphate buffer saline). Results were correlated with Korsmeyer-Peppas and Weibull model. Depending on the thymol content and chemical nature of the release medium, the time of thymol release varied from one to three days indicating CA as a promising carrier of thymol with potential uses from medicine to agriculture. The impregnated CA showed antibacterial activity against 23 tested bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA) which is particularly important bearing in mind that this strain causes fatal infections in humans and animals