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Synthesized nano particles of glimepiride via spray freezing into cryogenic liquid: characterization, antidiabetic activity, and bioavailability

Dalia A Gaber, Abdulrahman S Alhuwaymili, Hessah S Alhawas, Alhnouf A Almutiri, Amal M Alsubaiyel, Siham A Abdoun, Reem A Almutairi

Abstract

The aim of this work was to formulate glimepiride (class II drug) which is characterized by low solubility and high permeability as nanostructured particles using a cryogenic technique with an aid of water-soluble polymer to improve its aqueous solubility and hence its bioavailability. 27 formula of glimepiride nano size particles were prepared by a spray freezing into cryogenic liquid (SCFL) using poly vinyl pyrrolidone K-30 (PVP K-30); that three drug polymer ratio (1:1, 1:2, and 1:3), with three different volumes of feeding solution (50, 100, 150 mL), at three flow rates (10, 20, and 30 mL/min). The prepared formulations were evaluated for production yield, particle size, zeta potential, drug content, release rate, in vivo hypoglycemic activity, and bioavailability. All prepared formulations showed high production yield and drug content ranged between 91.1 ± 3.4% and 94.3 ± 1.8% and 95.1 ± 2.8% and 97.1 ± 2.5%, respectively. The mean particles size was ranged between 280 ± 62 nm and 520 ± 30 nm. The results of in vitro release study revealed significant enhancement in the solubility of prepared formulations compared with the pure drug. It was found that optimal formula showed a significant reduction in blood glucose levels in diabetic rats, and 1.79-fold enhancements in oral bioavailability compared with market tablets. Nanoparticle prepared by SCFL method is an encouraging formula for improving the solubility and the bioavailability of glimepiride.

Keywords

Antidiabetic; Glimepiride; bioavailability; cryogenic; nano size.

Ultrasonic spray freeze-drying of sucrose and mannitol-based formulations: Impact of the atomization conditions on the particle morphology and drying performance

Merve B. Adali, Antonello Barresi, Gianluca Boccardo, Giorgia Montalbano, Roberto Pisano

Abstract

Spray freeze-drying is an emerging manufacturing technology that offers many advantages, including long-term stability, consistent particle size distribution, and enhanced bioavailability. However, its implementation on an industrial scale is still hampered by several technical problems relating to the design of the equipment and the selection of appropriate operating conditions. This study aims to clarify the relationship between the atomization conditions (atomizing power, feed flow rate, and viscosity) and the characteristics of the lyophilized powder (particle size distribution and morphology) for two model products (sucrose- and mannitol-based formulations). Independently of the formulation, the particle morphology only depended on its solid content, while the average particle size increased with the feed flow rate and viscosity. Lastly, the specific surface area of the lyophilized powder varied with the initial solid content and the type of excipient as well, with mannitol-based particles having the highest specific surface area.

Keywords

Spray freeze-drying, freeze-drying, ultrasonic atomizer, particle morphology, particle size distribution, porous particles

Spray freeze drying to solidify Nanosuspension of Cefixime into inhalable microparticles

Samaneh Alaei, Elham Ghasemian, Alireza Vatanara

Abstract

Size reduction to a nanoscale is a relatively new approach to overcome solubility and bioavailability issues of many drugs such as cefixime (CFX). However, nanoparticles and specifically nanosuspensions are prone to many instabilities like aggregation and sedimentation. One of the main solutions is transforming liquid nanosuspension into dry powder. In this study, cefixime (CFX) nanosuspension was co-spray dried in the presence of different carriers (lactose, mannitol and sorbitol) in 3 ratios of nanoparticles (NPs)/carriers (1, 1.5 and 4 (w/w)). Physicochemical properties of the obtained powders were assessed in terms of particle size, morphology, thermal behavior, flowability, dissolution profile and aggregation over 6 months. Co-processing of NPs resulted in the formation of partially spherical particles with deeply wrinkled surfaces in the sizes ranging from 3.61 to 12.18 μm. Flowability showed improvement of all microparticles and thermal analysis demonstrated an amorphous state. Results suggest that among carriers, sorbitol based microparticles had the same dissolution profile as the initial NPs (29-fold increase in maximum solubility compared to unprocessed CFX) and could preserve reconstituted NPs’ size efficiently after storage. This shows the feasibility of using sorbitol as a promising carrier for spray drying of nanosuspensions which was mostly used for co-processing of solid lipid nanoparticles, proteins and peptides before.

Optimization of spray freeze drying parameters for spark plasma sintering of transparent MgAl2O4 spinel

Aref Basiri, Amir Hossein, Nassajpour-Esfahani, Mohammad Reza, Haftbaradaran-Esfahani, Amir Alhaji, Ali Shafyei

Abstract

Magnesium aluminate spinel (MgAl2O4) is considered as one of the most important spinels possessing desirable mechanical properties, with a wide range of applications at high temperatures. Powder granulation by spray freeze drying can lead to better powder flow and distribution in the mold, resulting in a specimen with high green density and strength. Accordingly, this study aimed at investigating the influential parameters on the granulation process of spinel powders via the spray freezing drying method. At first, spinel powders with various weight percents of 20, 25, 30, 35 and 50, and PVA binders with 0, 1, 2 and 8 wt% were investigated to prepare the optimal solution. Finally, the granules were sintered using the SPS method. The obtained bodies were tested by X-ray diffraction, SEM, FE-SEM, Viscosity and UV–Vis. The results showed that the optimal amount of the binder to obtain uniform granules in this process was 3%. Also, 35 wt% of solid loads represented the optimum amount for slurries, forming granules with the size range of 10–50 μm. By powder granulation, density experienced an increase of about 20%, leading to the growth of more than 15% in the in-line transmission for the IR range.

Keywords

Magnesium aluminate spinel, Spray freeze drying, Granulation, Spark plasma sintering

Polyphosphates as an effective vehicle for delivery of bioavailable nanoparticulate iron(III)

Shiyang Li, Tengjiao Guo, Wei Guo, Xuan Cui, Mingyong Zeng, Haohao Wu

Abstract

Polyphosphates are widely used food additives with the potential to increase iron bioavailability but chemical nature of their soluble complexes with iron remains largely unknown. Here, pyrophosphate, tripolyphosphate, hexametaphosphate and ∼25-chain-length polyphosphate solubilized 896, 896, 1120 and 1344 mg Fe(III) per g, respectively, at neutral pH by mediating the formation of highly-negatively-charged ferric hydroxide-polyphosphate nanoparticles (PolyP-FeONPs). PolyP-FeONPs displayed fading yellow color with increasing initial dissolved P/Fe ratio ((P/Fe)init) and decreasing polyphosphate length due to rising proportion of Fe(III)-phosphate bonds, and specifically, pyrophosphate resulted colorless PolyP-FeONPs at (P/Fe)init ≥ 4. PolyP-FeONPs had weak pro-oxidant activity in glyceryl trilinoleate emulsion and good colloidal stability under spray/freeze-drying and gastrointestinal conditions. Serum iron kinetics in rats revealed sustained iron release and ∼170% iron bioavailability of oral PolyP-FeONPs relative to FeSO4. Calcein-fluorescence-quenching assay in polarized Caco-2 cells unveiled divalent-metal-transporter-1-independent and macropinocytosis-dependent iron uptake from PolyP-FeONPs. This study helps develop food-compatible, highly-bioavailable and sustained-release iron preparations.

Keywords

Caco-2 cells; Endocytosis; Nanoparticles; Polyphosphates; Relative iron availability

Identification of Stability Constraints in the Particle Engineering of an Inhaled Monoclonal Antibody Dried Powder

Ashlee D Brunaugh, Li Ding, Tian Wu, Michael Schneider, Ryan Khalaf, Hugh D C Smyth

Abstract

Monoclonal antibody (mAb) based therapies may provide a valuable new treatment modality for acute and chronic lung diseases, including asthma, respiratory infections, and lung cancer. Currently mAbs are delivered via systemic administration routes, but direct delivery to the lungs via the inhaled route could provide higher concentrations at the site of disease and reduced off-target effects. Though lyophilized mAbs may be reconstituted and delivered to the lungs using nebulizers, dry powder inhalers provide a more patient-friendly delivery method based upon their fast administration time and portability. However, particle engineering processes required to prepare respirable dried powders for DPI delivery involve multiple potential stressors for mAbs, which have not been fully explored. In this study, a systematic examination of various aspects of the particle engineering process (atomization, freezing, drying, and storage) was performed to further understand their impact on mAb structure and aggregation. Using anti-streptavidin IgG1 as a model mAb, atomization settings were optimized using a design of experiments approach to elucidate the relationship between feed flow rate, formulation solid content, and atomization airflow rate and protein structural changes and aggregation. The optimized atomization conditions were then applied to spray drying and spray freezing drying particle engineering processes to determine the effects of freezing and drying on IgG1 stability and aerosol performance of the powders. IgG1 was found to be particularly susceptible to degradation induced by the expansive air-ice interface generated by spray freeze drying and this process also produced powders that exhibited decreased storage stability. This study further delineates the design space for manufacturing of respirable biologic therapies and is intended to serve as a roadmap for future development work.

Keywords

Monoclonal antibody; Particle engineering; Pulmonary drug delivery; Spray drying; Spray freeze drying; Stability

Spray-freeze-dried inhalable composite microparticles containing nanoparticles of combinational drugs for potential treatment of lung infections caused by Pseudomonas aeruginosa

Shihui Yu, XiaohuiPu, Maizbha Uddin Ahmed, Heidi H.Yu, Tarun Tejasvi Mutukuri, Jian Li, Qi Tony Zhou

Abstract

The multi-drug resistance of Pseudomonas aeruginosa is an overwhelming cause of terminal and persistent lung infections in cystic fibrosis (CF) patients. Antimicrobial synergy has been shown for colistin and ivacaftor, and our study designed a relatively high drug-loading dry powder inhaler formulation containing nanoparticles of ivacaftor and colistin. The ivacaftor-colistin nanosuspensions (Iva-Col-NPs) were prepared by the anti-solvent method with different stabilizers. Based on the aggregation data, the formulation 7 (F7) with DSPG-PEG-OMe as the stabilizer was selected for further studies. The F7 consisted of ivacaftor, colistin and DSPG-PEG-OMe with a mass ratio of 1:1:1. The F7 powder formulation was developed using the ultrasonic spray-freeze-drying method and exhibited a rough surface with relatively high fine particle fraction values of 61.4 ± 3.4% for ivacaftor and 63.3 ± 3.3% for colistin, as well as superior emitted dose of 97.8 ± 0.3% for ivacaftor and 97.6 ± 0.5% for colistin. The F7 showed very significant dissolution improvement for poorly water soluble ivacaftor than the physical mixture. Incorporating two drugs in a single microparticle with synchronized dissolution and superior aerosol performance will maximize the synergy and bioactivity of those two drugs. Minimal cytotoxicity in Calu-3 human lung epithelial cells and enhanced antimicrobial activity against colistin-resistant P. aeruginosa suggested that our formulation has potential to improve the treatment of CF patients with lung infections.

Keywords

Colistin, Ivacaftor, Cystic fibrosis, Pseudomonas aeruginosa, Dry powder inhaler, In vitro dissolution

Freeze granulation and spray drying of mixed granules of Al₂O₃

M. Singlard, A. Paillassa, L. Ferres, C. Pagnoux, A. Aimable

Abstract

This paper proposes a comparative study of two techniques of granulation of a submicronic alumina powder with high binder content slurries, by spray drying and freeze granulation for the preparation of mixed granules. First, the viscosity and flow index of the suspensions are given as a function of dispersant, solid and binder contents versus alumina content, and the data are analysed in order to give a predictive model in a wide range. Suspensions with varying viscosities (7–208 mPa.s), densities (1.31–1.76) and surface tensions (23–40 mN/m) were then granulated. The first observations reveal the importance of the content and the molar mass of the binder: when they are too high, the freeze granulation fails and filaments are produced instead of granules due to extensive stretching of the molecular chains of the binder during spraying. Then through a theoretical analysis of the phenomena leading to granulation, an original dimensionless number is proposed to describe the evolution of the granule size as a function of suspension formulation. This number is related to the Reynolds and Weber number and is able to predict the granule size over a wide range (20–500 μm for freeze granulation, and 5–30 μm for spray drying). Spray drying leads to smaller granules with various shapes, from full shape to hollow or donut-like, whereas freeze granulation leads to bigger but spherical granules with a microporosity, and a size easier to predict as no drying shrinkage is observed.

Keywords

Spray drying, Freeze granulation, Alumina, Size distribution, Binder, Granules

Full paper

Freeze Granulation of Nanoporous UiO-66 Nanoparticles for Capture of Volatile Organic Compounds

Van Nhieu Le, Daekeun Kim, Jinsoo Kim, Mohd Roslee Othman

Abstract

Nanoporous UiO-66 spherical beads prepared by using PVA binder successfully connected UiO-66 nanoparticles together into granular beads with improved mechanical strength for toluene capture. This was achieved without affecting the crystalline nature and micropore structures of the material. The regular octahedron of the UiO-66 individual nanoparticle remained intact, and the micropore size did not change with increasing PVA addition without which the nanoporous UiO-66 could not granulate into beads. However, PVA bound the nanoparticles together to form compact and cohesive network clusters that reduced the BET surface area and total pore volume. This consequently lowered the toluene adsorption efficacy slightly due to the premature breakthrough that limited the toluene molecular exposure into the micropores of the individual UiO-66 nanoparticles.

Keywords

UiO-66 nanoparticles, freeze granulation, VOC biomarker, microporous media, organic inorganic materials

Maximizing the enzyme immobilization of enzymatic glucose biofuel cells through hierarchically structured reduced graphene oxide

Joonyoung Lee, Kyuhwan Hyun, Jae Min Park, Ho Seok Park, Yongchai Kwon

Summary

The number of immobilized glucose oxidase (GOx) molecules is considerably increased by the structural modification of reduced graphene oxide (rGO), and the performance of enzymatic biofuel cells (EBFCs) is positively affected by the modification process. To do this, new rGO with three-dimensional open porous structure is formed by spray freeze drying method (sprGO), while tetrathiafulvalene (TTF) as mediator, and GOx are sequentially immobilized onto sprGO. To improve the loading amount of catalyst, rGO structure is modified to open porous sprGO structure possessing numerous anchoring sites, after which gelatin film crosslinked by glutaraldehyde is fabricated onto sprGO to prevent any losses of other components (sprGO/[TTF-GOx]/crosslinked-gelatin). Specific surface area and charge transfer resistance of sprGO are quantitatively measured, and the actual amount of immobilized GOx and the performance of EBFC using this catalyst are electrochemically examined. With this, it is found that the amount of GOx immobilized in sprGO/[TTF-GOx]/crosslinked-gelatin is twice better that in rGO/[TTF-GOx]/crosslinked-gelatin. More specifically, EBFC using this catalyst shows open circuit voltage of 0.85 V and maximum power density of 380 μW/cm2, and this is 1.4 times better than that using rGO/[TTF-GOx]/crosslinked-gelatin. These results indicate that the amount of immobilized GOx strongly affects the performance capabilities of EBFCs.

Keywords

biofuel cell, freeze-drying method, glucose oxidase, open porous structure, spray frozen reduced graphene oxide