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European Journal of Pharmaceutical... Feb 2024This study investigates the effect of different mixers and the applicability of the mixing energy (ME) concept to dry powder formulations for inhalation. With the aim to...
This study investigates the effect of different mixers and the applicability of the mixing energy (ME) concept to dry powder formulations for inhalation. With the aim to step-wise build and expand this concept, adhesive mixtures of 2 % budesonide and lactose carrier were investigated, both with 1 % magnesium stearate (MgSt) added in a 'coating' step, and without, the latter referred to as 'naked' formulations. For high shear mixed formulations, the fine particle fraction (FPF) was found to increase with increasing ME up to 60 % and thereafter decreased, using the Novolizer device. The data could be well fitted to the modeling equation, thus confirming the validity of the ME concept. The naked formulations displayed a linear decrease in FPF with increasing ME, again showing the validity of the ME concept. For Turbula mixed formulations, FPF increased with increased mixing time (and mixing energy) for all batches. The naked (binary) composition reached to higher FPF values than for high shear mixing and the formulation with MgSt reached to FPF values around 60 %, demonstrating that it is possible to achieve the same high drug dispersibility with the Turbula mixer as for high shear mixer. An equation for calculation of mixing energy in Turbula mixing was set up in an analogous way to the equation for high shear mixing, which enabled direct comparison between the two mixers.
Topics: Chemistry, Pharmaceutical; Adhesives; Drug Carriers; Administration, Inhalation; Budesonide; Powders; Particle Size; Lactose; Dry Powder Inhalers
PubMed: 38128841
DOI: 10.1016/j.ejps.2023.106679 -
Green Chemistry : An International... Dec 2023The inferior thermoplastic properties have limited production of melt-spun fibers from lignin. Here we report on the controlled esterification of softwood kraft lignin...
The inferior thermoplastic properties have limited production of melt-spun fibers from lignin. Here we report on the controlled esterification of softwood kraft lignin (SKL) to enable scalable, solvent-free melt spinning of microfibers using a cotton candy machine. We found that it is crucial to control the esterification process as melt-spun fibers could be produced from lignin oleate and lignin stearate precursors with degrees of esterification (DE) ranging from 20-50%, but not outside this range. To fabricate a functional hybrid material, we incorporated magnetite nanoparticles (MNPs) into the lignin oleate fibers by melt blending and subsequent melt spinning. Thermogravimetric analysis and X-ray diffraction studies revealed that increasing the weight fraction of MNPs led to improved thermal stability of the fibers. Finally, we demonstrated adsorption of organic dyes, magnetic recovery, and recycling melt spinning of the regular and magnetic fibers with 95% and 83% retention of the respective adsorption capacities over three adsorption cycles. The mechanical recyclability of the microfibers represents a new paradigm in lignin-based circular materials.
PubMed: 38089756
DOI: 10.1039/d3gc02381h -
Scientific Reports Dec 2023Food emulsifier are mostly prepared from a lipophilic lipid tail with a hydrophilic sugar head. In this study, the lipophilic tail was obtained from apricot kernels,...
Food emulsifier are mostly prepared from a lipophilic lipid tail with a hydrophilic sugar head. In this study, the lipophilic tail was obtained from apricot kernels, which are food waste, and the hydrophilic head was gluconic acid instead of sugar, in order to draw attention to the non-cyclic poly hydroxyl compounds. Thus, oleic acid of apricot kernel was used as the lipophilic moiety of the prepared surfactant. So, apricot kernel was grinned and dried, oil was extracted using soxhlet apparatus, Physical and chemical parameters and fatty acids composition of the extracted oil had been determined. The extracted oil was then hydrolyzed into glycerol and a mixture of free fatty acids. The fatty acids mixture was separated. Then, oleic acid was extracted individually in pure form using supercritical CO extractor, it was then confirmed according to its melting point, Gas chromatography-mass spectrometry (GC-MS) after esterification, elemental analysis, Proton nuclear magnetic resonance (HNMR), and mass spectrometry (MS) to detect the corresponding molecular ion peak. The pure individual oleic acid was converted to hydroxy stearic acid, which was then converted to an amphiphilic compound (surfactant) via esterification reaction with the hydrophilic gluconic acid, and afforded a new surfactant known as 2,3,4,5-tetrahydroxy-6-((9-((-2,3,4,5,6-pentahydroxyhexanoyl) oxy)octadecanoyl) oxy)hexanoic acid or stearyl gluconate for simplification. The structures elucidation of all synthesized compound was established according to elemental analysis and spectral data (Fourier transform infrared IR, H NMR, C NMR and MS). Moreover, the prepared compound was tasted for its antibacterial activity, and showed good activities against some types of bacteria. The surface-active properties, foamability, foaming stability and emulsion stability of stearyl gluconate were studied and compared with the properties of the well-known surfactant sucrose stearate, and it was clear that, the activity of stearyl gluconate as a surfactant was higher than that of sucrose stearate. Moreover, establishment of safety of this compound was performed using albino rats by acute oral toxicity and kidney and liver functions of these mice. On the other hand, the prepared surfactant was used in the production of low fat-free cholesterol mayonnaise as egg replacer. Texture properties and the sensory evaluation of the prepared mayonnaise showed that the properties were improved by using the new prepared surfactant. Thus, the prepared gluconyl stearate can be used as a safe food additive.
Topics: Rats; Mice; Animals; Prunus armeniaca; Surface-Active Agents; Food; Refuse Disposal; Plant Oils; Fatty Acids; Gluconates; Anti-Bacterial Agents; Sugars; Oleic Acids
PubMed: 38057365
DOI: 10.1038/s41598-023-48404-x -
Chemical & Pharmaceutical Bulletin 2023Direct compression is a tableting technique that involves a few steps in non-demanding manufacturing conditions. High strength and rapid disintegration of tablet...
Direct compression is a tableting technique that involves a few steps in non-demanding manufacturing conditions. High strength and rapid disintegration of tablet formulations were previously achieved through the addition of cellulose nanofibers (CNFs), which have recently attracted attention as a high-performance biomass material. However, CNF addition results in greater variation in tablet weight and drug content, potentially due to differences in particle size between CNF and other additives. Herein, we used pulverized CNF to evaluate the effect of CNF particle size on the variation in tablet weight and drug content. Tablet formulations consisted of CNF with different particle sizes (approximately 100 µm [CNF] and 300 µm [CNF], at 0, 10, 30, or 50%), lactose hydrate, acetaminophen, and magnesium stearate. Ten powder formulations with different particle sizes and CNF concentrations were prepared; thereafter, the tablets were produced using a rotary tableting press with a compression force of 10 kN. The variation in weight and drug content as well as the tensile strength, friability, disintegration time, and drug dissolution of tablets were evaluated. CNF addition to the tablets reduced the weight and drug content variation to a greater extent than CNF addition. Using CNF, we produced tablets of sufficient strength and short disintegration time. These properties were also achieved with CNF addition. Our findings suggest that adding CNF of small particle size to the tablet formulation can reduce the variation in weight and drug content while maintaining high strength and short disintegration time.
Topics: Particle Size; Drug Compounding; Nanofibers; Cellulose; Tensile Strength; Tablets
PubMed: 38044141
DOI: 10.1248/cpb.c23-00587 -
Pharmaceutics Nov 2023Modern pharmaceutical manufacturing based on Quality by Design and digitalisation is revolutionising the pharmaceutical industry. Continuous processes are promoted as...
Modern pharmaceutical manufacturing based on Quality by Design and digitalisation is revolutionising the pharmaceutical industry. Continuous processes are promoted as they increase efficiency and improve quality control. Compared to batch blending, continuous blending is easier to scale and provides advantages for achieving blend homogeneity. One potential challenge of continuous blending is the risk of over-lubrication. In this study, blending homogeneity and lubricant sensitivity are investigated for both batch and continuous processes. Given their distinct chemical structures and morphologies, anhydrous lactose and granulated lactose are expected to exhibit varying sensitivities to changes in process settings across both technologies. The findings suggest that both lactose grades provide highly stable blends that can be safely utilised in both batch and continuous modes. Optimisation should focus on process variables, such as the quality of loss-in-weight feeders used for dosing low doses of ingredients. The most significant process parameter for lubricant sensitivity was the type of lactose used. Anhydrous lactose produced harder tablets than the more porous granulated lactose but was more sensitive to lubrication at the same settings. The magnesium stearate content and its interaction with the type of lactose are also critical factors, with magnesium stearate having a counterproductive impact on tabletability.
PubMed: 38004554
DOI: 10.3390/pharmaceutics15112575 -
Pharmaceuticals (Basel, Switzerland) Nov 2023Cationic solid-lipid nanoparticles (cSLNs) have become a promising tool for gene and RNA therapies. PEGylation (PEG) is crucial in enhancing particle stability and...
Cationic solid-lipid nanoparticles (cSLNs) have become a promising tool for gene and RNA therapies. PEGylation (PEG) is crucial in enhancing particle stability and protection. We evaluated the impact of PEG on the physicochemical and biological characteristics of cholesteryl-oleate cSLNs (CO-cSLNs). Several parameters were analyzed, including the particle size, polydispersity index, zeta potential, shape, stability, cytotoxicity, and loading efficiency. Five different formulations with specific PEGs were developed and compared in both suspended and freeze-dried states. Small, homogeneous, and cationic suspended nanoparticles were obtained, with the Gelucire 50/13 (PEG-32 hydrogenated palm glycerides; Gelucire) and DSPE-mPEG2000 (1,2-distearoyl-phosphatidylethanolamine-methyl-polyethyleneglycol conjungate-2000; DSPE) formulations exhibiting the smallest particle size (~170 nm). Monodisperse populations of freeze-dried nanoparticles were also achieved, with particle sizes ranging from 200 to 300 nm and Z potential values of 30-35 mV. Notably, Gelucire again produced the smallest particle size (211.1 ± 22.4), while the DSPE and Myrj S100 (polyoxyethylene (100) stearate; PEG-100 Stearate) formulations had similar particle sizes to CO-cSLNs (~235 nm). The obtained PEGylated nanoparticles showed suitable properties: they were nontoxic, had acceptable morphology, were capable of forming SLNplexes, and were stable in both suspended and lyophilized states. These PEG-cSLNs are a potential resource for in vivo assays and have the advantage of employing cost-effective PEGs. Optimizing the lyophilization process and standardizing parameters are also recommended to maintain nanoparticle integrity.
PubMed: 38004448
DOI: 10.3390/ph16111583 -
ACS Biomaterials Science & Engineering Dec 2023Nanoemulsions can be tuned toward enhanced gastro-intestinal retention time by incorporating thiolated surfactants into their surface. Tailoring the chemical reactivity...
Nanoemulsions can be tuned toward enhanced gastro-intestinal retention time by incorporating thiolated surfactants into their surface. Tailoring the chemical reactivity of the thiol headgroup has major influence on mucoadhesive features of the nanoemulsion. Two generations of thiolated surfactants were synthetically derived from PEG-40-stearate featuring either a free thiol group or an S-protected thiol group. The surfactants were characterized regarding critical micelle concentration (CMC), hemolytic activity, and cytotoxicity. Subsequently, they were incorporated into nanoemulsions and the resulting nanoemulsions were characterized regarding particle size, polydispersity index (PDI), zeta potential, and time-dependent stability. Afterward, mucosal interactions as well as mucoadhesion on porcine intestinal mucosa were investigated. Successful synthesis of Cysteine-PEG-40-stearate (CYS-PEG-40-stearate) and MNA-Cysteine-PEG-40-stearate (MNA-CYS-PEG-40-stearate) was confirmed by H NMR spectroscopy. Both chemical modifications led to slightly elevated CMC values while preserving low cytotoxicity and hemotoxicity. Incorporation into nanoemulsions had minor influence on overall physical particle characteristics, while interactions with mucus and mucoadhesiveness of the nanoemulsions were drastically improved resulting in the rank order PEG-40-stearate < CYS-PEG-40-stearate < MNA-CYS-PEG-40-stearate. Accordingly, thiolated surfactants, especially S-protected derivatives, are versatile tools to generate highly mucoadhesive nanoemulsions.
Topics: Animals; Swine; Cysteine; Drug Delivery Systems; Surface-Active Agents; Stearates; Sulfhydryl Compounds
PubMed: 37996083
DOI: 10.1021/acsbiomaterials.3c01207 -
Journal of Pharmaceutical Sciences Feb 2024An improved agglomerate formulation with melatonin and fine lactose for dry powder inhalation using Turbuhaler® was developed. Co-grinding lactose with 1 % magnesium...
An improved agglomerate formulation with melatonin and fine lactose for dry powder inhalation using Turbuhaler® was developed. Co-grinding lactose with 1 % magnesium stearate prior to air jet mixing served as a key factor to improve the in vitro aerosolization and in vivo efficacy. Elevated mixing pressure facilitated the dispersion and homogenization of the cohesive mixture for even distribution of agglomerate size after spheroidization and subsequent higher emitted dose with lower variation. Magnesium stearate was employed as a tertiary component to adjust the interparticle force for better aerosolization. At optimized mixing pressure, co-grinding lactose with magnesium stearate before jet mixing displayed further improvement of fine particle fraction to 71.6 ± 3.1 %. The superior fine particle deposition efficiency contributed to rapid onset of action and a high bioavailability of 67.0 % after intratracheal administration to rats. Overall, an inhalable melatonin dry powder formulation exhibiting good aerosol property and lung deposition with clinical translation potential was developed.
Topics: Animals; Rats; Powders; Melatonin; Lactose; Administration, Inhalation; Aerosols; Particle Size; Dry Powder Inhalers
PubMed: 37995838
DOI: 10.1016/j.xphs.2023.11.016 -
International Journal of Molecular... Oct 2023In this study, we developed a tamsulosin pellet-loaded orally disintegrating tablet (ODT) that is bioequivalent to commercially available products and has improved...
In this study, we developed a tamsulosin pellet-loaded orally disintegrating tablet (ODT) that is bioequivalent to commercially available products and has improved patient compliance using microcrystalline cellulose (MCC) and mannitol. Utilizing the fluid bed technique, the drug, sustained release (SR) layer, and enteric layer were sequentially prepared by coating MCC pellets with the drug, HPMC, Kollicoat, and a mixture of Eudragit L and Eudragit NE, respectively, resulting in the production of tamsulosin pellets. The tamsulosin pellet, composed of the MCC pellet, drug layer, SR layer, and enteric layer at a weight ratio of 20:0.8:4.95:6.41, was selected because its dissolution was equivalent to that of the commercial capsule. Tamsulosin pellet-loaded ODTs were prepared using tamsulosin pellets and various co-processed excipients. The tamsulosin pellet-loaded ODT composed of tamsulosin pellets, mannitol-MCC mixture, silicon dioxide, and magnesium stearate at a weight ratio of 32.16:161.84:4.0:2.0 gave the best protective effect on the coating process and a dissolution profile similar to that of the commercial capsule. Finally, no significant differences in beagle dogs were observed in pharmacokinetic parameters, suggesting that they were bioequivalent. In conclusion, tamsulosin pellet-loaded ODTs could be a potential alternative to commercial capsules, improving patient compliance.
Topics: Humans; Dogs; Animals; Tamsulosin; Mannitol; Delayed-Action Preparations; Solubility; Tablets; Excipients
PubMed: 37895073
DOI: 10.3390/ijms242015393 -
ACS Omega Oct 2023Indomethacin as a non-steroidal anti-inflammatory drug (NSAID) is commonly used to treat some ocular inflammatory disorders. Unfortunately, indomethacin is a drug that...
Indomethacin as a non-steroidal anti-inflammatory drug (NSAID) is commonly used to treat some ocular inflammatory disorders. Unfortunately, indomethacin is a drug that is poorly soluble in water; therefore, it has low efficacy. An attractive approach is the targeted delivery of indomethacin to the cornea using cationic dextran stearate as a polymeric micelle drug carrier. A dextran stearate-glycidyl trimethylammonium chloride (Dex-St-GTMAC) copolymer was prepared through the reaction of GTMAC, stearoyl chloride, and dextran. Then, Dex-St-GTMAC was characterized by Fourier transform infrared (FT-IR) spectroscopy and H NMR spectroscopy. Dex-St-GTMAC forms micelles in the presence of indomethacin. The prepared polymeric micelles were characterized for size, ζ-potential, drug loading, particle morphology, critical micelle concentration, and encapsulation efficiency. To study the irritation potential of the indomethacin-loaded Dex-St-GTMAC, Het-Cam and Draize tests have been performed. Prepared cationic micelles were subjected to the drug release and -corneal permeation test. The dialysis method was used for the preparation of indomethacin-loaded micelles (10, 20, and 30%). Measurement of the particle size showed a mean diameter of 122.1 and 150.9 nm for the drug-loaded micelles. Scanning electron microscopy (SEM) images showed that the morphology of the particles is spherical. 10% formulation was chosen as the best formulation due to more surface charge and reasonable drug loading. ζ-potential measurement for the 10% drug-containing micelles showed a value of +39.1 mV. Drug loading efficiency and the encapsulation efficiency for 10% drug-containing micelles were 6.36 and 63.61%, respectively. The results of the Het-Cam and Draize tests indicated that the indomethacin-loaded Dex-St-GTMAC formulation had no toxicity to eye tissues. Based on our results, the prepared micelles (indomethacin-loaded Dex-St-GTMAC) exhibited a sustained drug release pattern compared to the control group. Indomethacin penetration from the micelles to the excised bovine cornea was 1.75-fold greater than the control (indomethacin 0.1% in phosphate-buffered saline (PBS)). Data from the ζ-potential, SEM, drug loading capacity, and drug release studies indicated that cationic dextran stearate polymeric micelles are an appropriate carrier for the efficient penetration of indomethacin into cornea tissues.
PubMed: 37867673
DOI: 10.1021/acsomega.3c04187