Nano spray drying has emerged as an outstanding platform for engineering micro- and nanoparticles, with growing applications in various areas of drug delivery. As a new technology involving distinct technical design, parameters of the nano spray drying process are not fully elucidated. In a quality-by-design approach, the aim of the current study was to gain thorough understanding of critical determinants of product characteristics in the Büchi Nano Spray Dryer B-90. Following a factorial experimental design, a series of spray drying experiments were conducted to gain new insights into the influences of the inlet temperature, the spray solvent, and the solute concentration in the spray solution on the yield, the moisture content, and the particle size of the nano spray-dried powder material. Special consideration was given to the potential of using hydroethanolic in comparison with aqueous solvent systems and to particle engineering for pulmonary drug delivery. Lactose and mannitol, widely used as excipients in dry powder inhalation formulations, were used as model materials. Lactose and mannitol are known to spray dry in amorphous and crystalline forms, respectively. The yields of spray drying of lactose and mannitol amounted generally to 71.1 ± 6.6% w/w and 66.1 ± 3.5% w/w, respectively. The spray-dried materials exhibited generally a number-weighted median particle diameter of 1.6 ± 0.2 μm and a volume-weighted median particle diameter of 5.1 ± 1.0 μm. A detailed analysis of the results improved understanding of the interplay between process parameters in the Nano Spray Dryer. The results demonstrate that optimization of spray generation is the key to yield optimization. On the other hand, particle size is determined by the spray mesh pore size and the spray solution degree of saturation. Selection of an appropriate spray solvent and using spray solution additives could optimize spray flow. In parallel, the spray solvent and the solute concentration in the spray solution determine the degree of saturation. Guidance on optimization of particle engineering by nano spray drying is provided.
Ibuprofen is a well-known non-steroidal anti-inflammatory (NSAID) medicine that is often used to treat inflammation in general. When given orally, it produces gastrointestinal issues which lead to lower patient compliance. Ibuprofen transdermal administration improves both patient compliance and the efficacy of the drug. Nanoconjugation hydrogels were proposed as a controlled transdermal delivery tool for ibuprofen. Six formulations were prepared using different compositions including chitosan, lipids, gum arabic, and polyvinyl alcohol, through ionic interaction, maturation, and freeze–thaw methods. The formulations were characterised by size, drug conjugation efficiency, differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). Further analysis of optimised hydrogels was performed, including X-ray diffraction (XRD), rheology, gel fraction and swelling ability, in vitro drug release, and in vitro macrophage prostaglandin E2 (PGE2) production testing. The effects of ibuprofen’s electrostatic interaction with a lipid or polymer on the physicochemical and dissolution characterisation of ibuprofen hydrogels were evaluated. The results showed that the S3 (with lipid conjugation) hydrogel provided higher conjugation efficiency and prolonged drug release compared with the S6 hydrogel.
29 December 2022 in International Journal of Pharmaceutics
The stability of the medicinal product is a major concern in the pharmaceutical industry and health authorities, whose goal is to guarantee that drugs are delivered to patients without loss of therapeutic properties. This study aims to evaluate the effect of environmental conditions and packaging on the stability of paracetamol instant jelly sachets based on both chemical and physical stability. The paracetamol instant jelly was packaged in plastic sachets (packaging 1) and sealed aluminium bags in screw-capped amber glass bottles (packaging 2), which were stored in real-time and accelerated stability chambers for 3 months. Samples were taken out from the chambers and were characterised for appearance, moisture content, texture, viscosity, in vitro drug release, paracetamol content, and 4-aminophenol level at different time points. The real-time storage condition at a lower temperature maintained the stability of the paracetamol instant jelly, while the accelerated condition led to a significant change in the formulation properties. In addition, the proper packaging of paracetamol instant jelly maintained the paracetamol’s stability, regardless of environmental conditions, for three months. The results show that the environmental conditions and packaging play a significant role in maintaining paracetamol instant jelly stability.
Terbinafine is a broad-spectrum antifungal agent with therapeutic potential against pulmonary aspergillosis. The main aim of the current study was to investigate the potential of l-leucine, alone and in combination with mannitol, to improve the performance of spray-dried terbinafine microparticles for inhalation. The study also aimed to investigate the potential of the low resistance Cyclohaler® and the high resistance Handihaler® as inhalation devices for spray-dried microparticles. To this end, eight powder inhalation formulations of terbinafine were prepared by nano spray drying via a factorial experimental design. The formulations were evaluated in vitro for their potential to deliver the antifungal drug to the lungs using the Cyclohaler® and the Handihaler®. Leucine was superior as an excipient to mannitol and to mixtures of leucine and mannitol. Using leucine as an excipient resulted in formulations with fine particle fractions of up to 60.84 ± 0.67% w/w and particle mass median aerodynamic diameters of down to 1.90 ± 0.20 μm, whereas using mannitol as an excipient resulted in formulations with fine particle fractions of up to 18.75 ± 3.46% w/w and particle mass median aerodynamic diameters of down to 6.79 ± 0.82 μm. When leucine was used as an excipient, using 50% w/w rather than 25% w/w ethanol in water as a spray solvent enhanced the dispersibility of the particles, with a mean absolute increase in the formulation fine particle fraction of 9.57% w/w (95% confidence interval = 6.40–12.73% w/w). This was potentially underlain by enrichment of the particle surfaces with leucine. The Cyclohaler® outperformed the Handihaler® as an inhalation device for the developed formulations, with a mean absolute increase in the fine particle fraction of 9.17% w/w (95% confidence interval = 8.17–10.16% w/w).
22 February 2024 in Notulae Botanicae Horti Agrobotanici Cluj-Napoca
Most Arab nations have arid regions where Ephedratransitoria, a plant, flourishes. It has a variety of medical benefits. It belongs to the Ephedraceae family. The plant's aerial portions were procured from the Hail region of Saudi Arabia, methanol was used to extract bioactive phytochemicals with variable solubility in an efficient manner, and the resulting extract was tested on several cancer cell lines. The extract's cytotoxic potential was measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay method against standard vinblastine sulfate and for each cell line, the pertinent half maximal inhibitory concentration values were calculated. Additional apoptosis assays were conducted. Also, the antioxidant activity of plant extract was examined using 2, 2-Diphenyl-1-picrylhydrazyl and [2, 2’-azinobis-(3-ethylbenzothiazoline-6-sulfonate)] methods compared to ascorbic acid standard. Also, antimicrobial effect of extract was evaluated on different gram positive and gram-negative bacteria by zone inhibition and minimum inhibitory concentration assay methods. GC-MS analysis was further applied to identify major bioactive substances. Extract showed good cytotoxic activity against both lung and liver cancer cells with relevant half maximal inhibitory concentration values comparable to those of standard. Extract resulted in S-phase arrest, primarily via inducing apoptosis mediated through activating caspase-3, Bax, and p53 proteins. Plant extract showed good antibacterial activities against S. aureus, E. coli and B. subtilis. Also, it showed high antioxidant activity with relevant half maximal inhibitory concentration values comparable to those of standard. Some bioactive compounds were separated and identified by GC-MS analysis such as; ephedrine and quercetin. ephedra transitoria extract possess high cytotoxic activity against lung and liver cancer cells via S-phase arrest mediated by activation of apoptotic proteins. It also possesses high antioxidant and antibacterial activities.