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Fabricating high-loading ultra-small PtCu3/rGO via a traceless protectant and spray-freeze-drying method

Qingyu Luo, Wei Xu, Shaolong Tang

Abstract

Exploring excellent catalysts for oxygen reduction reaction (ORR) with a facile and cost-effective method is desirable but remains challenging. Herein, ultra-small PtCu₃ nanoparticles (ca. 2.7 nm), immobilized on reduced graphene oxide (rGO), were synthesized via a novel and general strategy. Traceless protectant, NH₄OH, was used to resist the aggregation of graphene oxide (GO), and the spray-freeze-drying method ensures excellent dispersion of the Pt and Cu precursors, which could not be achieved by other reported drying methods. After annealing, the nanoparticles with the highest mass loading, 52%, among reported ordered Pt-based catalysts were obtained. The PtCu₃/rGO shows a remarkable electrocatalytic performance. Density functional theory calculations elucidate that PtCu₃ possess a lowered energy barrier of the rate-determining step, contributing to significantly improved ORR kinetics. This strategy was extended to the synthesis of other binary- and quaternary-metallic Pt-based nanoparticles, which proved its generality and applicability towards the potential commercialization of fuel cell technologies.

Keywords

Spray-freeze-drying, Traceless protectant, High-loading, Ultra-small, Oxygen reduction reaction

Designing highly porous amorphous celecoxib particles by spray freeze drying leads to accelerated drug absorption in-vivo

Dominic Lucas, Jan Kožák, Annika Rautenberg, Claire Chrétien, Yann Pellequer, Alf Lamprecht

Abstract

Poorly water-soluble drugs are still a major challenge to overcome in order to achieve sufficiently high oral bioavailability. Spray freeze drying (SFD) is proposed here as an alternative for the preparation of amorphous, free-flowing porous celecoxib spheres for enhanced drug dissolution. Tertiary butyl alcohol solutions of celecoxib + excipient (povidone, hydroxypropyl methylcellulose acetate succinate (HPMC-AS) and Soluplus®) at variable ratios were sprayed into a cooled spray tower, followed by vacuum freeze drying. Final porous particles were free-flowing, highly spherical (circularity ≥ 0.96) and mean diameters ranging from 210 to 800 µm, depending on excipient and drug content. XRPD measurements showed that Celecoxib was amorphous in all formulations and remained stable during 6 months storage. Kollidon 25 and HPMC-AS combinations resulted in the highest dissolution rates as well as dissolved drug amounts (30.4 ± 1.5 µg/ml and 41.8 ± 1.7 µg/ml) which in turn was 2-fold and 1.3-fold increase compared to film casted amorphous reference formulations, respectively. This phenomenon also translated into a faster onset of the drug absorption in-vivo, with significantly lower tmax values, while AUC values were non-significantly lowered compared to amorphous references. The high porosity of SFDs led to the advantageous accelerated dissolution which also translated into faster onset of absorption in-vivo.

Keywords

Spray freeze drying, Amorphous solid dispersions, Lyospheres, Porous particles, Poorly water-soluble

Dual targeting powder formulation of antiviral agent for customizable nasal and lung deposition profile through single intranasal administration

Han Cong Seow, Qiuying Liao, Andy T Y Lau, Susan W S Leung, Shuofeng Yuan, Jenny K W Lam

Abstract

Unpredictable outbreaks due to respiratory viral infections emphasize the need for new drug delivery strategies to the entire respiratory tract. As viral attack is not limited to a specific anatomic region, antiviral therapy that targets both the upper and lower respiratory tract would be most effective. This study aimed to formulate tamibarotene, a retinoid derivative previously reported to display broad-spectrum antiviral activity against influenza and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), as a novel dual particle size powder formulation that targets both the nasal cavity and the lung by a single route of intranasal administration. Spray freeze drying (SFD) and spray drying (SD) techniques were employed to prepare tamibarotene powder formulations, and cyclodextrin was used as the sole excipient to enhance drug solubility. With the employment of appropriate atomizing nozzles, particles of size above 10 μm and below 5 μm could be produced for nasal and lung deposition, respectively. The aerosol performance of the powder was evaluated using Next Generation Impactor (NGI) coupled with a glass expansion chamber and the powder was dispersed with a nasal powder device. By blending powder of two different particle sizes, a single powder formulation with dual aerosol deposition characteristic in both the nasal and pulmonary regions was produced. The aerosol deposition fractions in the nasal cavity and pulmonary region could be modulated by varying the powder mixing ratio. All dry powder formulations exhibited spherical structures, amorphous characteristics and improved dissolution profile as compared to the unformulated tamibarotene. Overall, a novel dual targeting powder formulation of tamibarotene exhibiting customizable aerosol deposition profile was developed. This exceptional formulation strategy can be adopted to deliver other antimicrobial agents to the upper and lower airways for the prevention and treatment of human respiratory infections.

Keywords

Antiviral agent; COVID-19; Dry powder aerosol; Intranasal delivery; Pulmonary delivery; Spray drying; Spray freeze drying

Encapsulation of probiotics: past, present and future

R. Rajam & Parthasarathi Subramanian

Abstract – Background

Probiotics are live microbial supplements known for its health benefits. Consumption of probiotics reported to improve several health benefits including intestinal flora composition, resistance against pathogens. In the recent years, there is an increasing trend of probiotic-based food products in the market.

Keywords

Probiotics, Viability, Encapsulation, Spray drying, Digestion, Storage, Denaturation

PRELIMINARY STUDY OF INSULIN DRY POWDER FORMULATION: CRITICAL PROCESS PARAMETERS ON SPRAY-FREEZE-DRYING AND CRITICAL MATERIAL ATTRIBUTES OF TREHALOSE AND INULIN AS STABILIZER

CYNTHIA MARISCA MUNTU, SILVIA SURINI, CHRISTINA AVANTI, HAYUN, WOUTER HINRICHS

Abstract

Objective: The aim of this study was to obtain recommendations about critical process parameters (CPP) and optimal ratio of trehalose and inulin as critical material attribute (CMA) on insulin dry powder formulation with spray-freeze-drying (SFD) method. Methods: Inulin dry powder was formulated with the SFD method, which consisted of an atomization process and freeze-drying (FD). SFD processes were optimized in order to obtain dry powder and CPP was analyzed. All seven variations of formulas proceeded with physicochemical characterization to obtain the optimal formula. Results: In the early optimization, there was a slight time lag between the atomization process and FD; as a result, some of the powder coagulated and crystallized. Another critical parameter was that the FD process should not be interrupted for at least 50 h of FD. Dry powder proceeded with physicochemical characterization, a formula without inulin showed semicrystalline properties, while six formulas had amorphous properties due to its combination. All formulas had a spherulite shape and rough surface. Five formulas with the combination of trehalose and inulin obtained dry powders with a diameter range of 30-43 μm, moisture content below 3.5% and high encapsulation efficiency (EE). Formula with the ratio of 1:1 (F4) showed optimal properties with moisture content and EE of 2.62% and 99.68%, respectively. Conclusion: This study concluded that there were two critical process parameters in the SFD method. There should be no time lag in SFD process and FD time which should not be interrupted. The optimal ratio for trehalose and inulin was shown by F4 with ratio of 1:1.

Keywords

Process Parameters, Freeze Drying, Time Lag, Physicochemical Characterization, Dry Powder, Critical Material, Atomization Process, Critical Process Parameters, Spray Freeze Drying, Critical Process

Emerging Technologies and Coating Materials for Improved Probiotication in Food Products: a Review

Sourav Misra, Pooja Pandey, Chandrakant Genu Dalbhagat, Hari Niwas Mishra

Abstract

From the past few decades, consumers’ demand for probiotic-based functional and healthy food products is rising exponentially. Encapsulation is an emerging field to protect probiotics from unfavorable conditions and to deliver probiotics at the target place while maintaining the controlled release in the colon. Probiotics have been encapsulated for decades using different encapsulation methods to maintain their viability during processing, storage, and digestion and to give health benefits. This review focuses on novel microencapsulation techniques of probiotic bacteria including vacuum drying, microwave drying, spray freeze drying, fluidized bed drying, impinging aerosol technology, hybridization system, ultrasonication with their recent advancement, and characteristics of the commonly used polymers have been briefly discussed. Other than novel techniques, characterization of microcapsules along with their mechanism of release and stability have shown great interest recently in developing novel functional food products with synergetic effects, especially in COVID-19 outbreak. A thorough discussion of novel processing technologies and applications in food products with the incorporation of recent research works is the novelty and highlight of this review paper.

Keywords

Drying; Functional foods; Microencapsulation; Packaging condition; Probiotics; Storage

Complete Protection Against Yersinia pestis in BALB/c Mouse Model Elicited by Immunization With Inhalable Formulations of rF1-V10 Fusion Protein via Aerosolized Intratracheal Inoculation

Wei Zhang, Xiaolin Song, Lina Zhai, Jianshu Guo, Xinying Zheng, Lili Zhang, Meng Lv, Lingfei Hu, Dongsheng Zhou, Xiaolu Xiong and Wenhui Yang

Abstract

Pneumonic plague, caused by Yersinia pestis, is an infectious disease with high mortality rates unless treated early with antibiotics. Currently, no FDA-approved vaccine against plague is available for human use. The capsular antigen F1, the low-calcium-response V antigen (LcrV), and the recombinant fusion protein (rF1-LcrV) of Y. pestis are leading subunit vaccine candidates under intense investigation; however, the inability of recombinant antigens to provide complete protection against pneumonic plague in animal models remains a significant concern. In this study, we compared immunoprotection against pneumonic plague provided by rF1, rV10 (a truncation of LcrV), and rF1-V10, and vaccinations delivered via aerosolized intratracheal (i.t.) inoculation or subcutaneous (s.c.) injection. We further considered three vaccine formulations: conventional liquid, dry powder produced by spray freeze drying, or dry powder reconstituted in PBS. The main findings are: (i) rF1-V10 immunization with any formulation via i.t. or s.c. routes conferred 100% protection against Y. pestis i.t. infection; (ii) rF1 or rV10 immunization using i.t. delivery provided significantly stronger protection than rF1 or rV10 immunization via s.c. delivery; and (iii) powder formulations of subunit vaccines induced immune responses and provided protection equivalent to those elicited by unprocessed liquid formulations of vaccines. Our data indicate that immunization with a powder formulation of rF1-V10 vaccines via an i.t. route may be a promising vaccination strategy for providing protective immunity against pneumonic plague.

Keywords

Yersinia pestis, pneumonic plague, subunit vaccine, rF1-V10, dry powder formulation, aerosolized intratracheal inoculation, mucosal immune response

Stability of spouted bed during spray cold coating on the surface of carrier particles

Fan Zhang, Linsong Wang, Qing Xu, Wei Tian and Zhanyong Li

Abstract

The rapid freezing of droplets on the surface of cold carrier particles can reduce the spray freeze-drying time. The coating freezing process can be treated in batch by using a spouted bed and the bed stability is the key. The freezing process of droplets would agglomerate the carrier particles. By analyzing the standard deviation of the bed pressure drop and the fluctuation of the bed pressure, the stable operating conditions of the spouted bed under cold coating were studied, and a dynamic adjustment method of the inlet air velocity to maintain stable spouting was proposed. The results show that the stable operating air velocity range can be described useing the standard deviation of pressure fluctuations. Before bed collapse occurs, it will experience an unstable spouting process, which causes the bed pressure to fluctuate a standard deviation of less than 15 Pa after more than 40 Pa.

Keywords

cold coating; dynamic adjust; spouted bed; sprayfreeze drying; stability

Development of drug alone and carrier-based GLP-1 dry powder inhaler formulations

Mai Babenko, Raid G. Alany, Gianpiero Calabrese, Waseem Kaialy, Amr ElShaer

Abstract

The study aimed to develop two types of dry powder inhaler (DPI) formulations containing glucagon-like peptide-1(7–36) amide (GLP-1): carrier-free (drug alone, no excipients) and carrier-based DPI formulations for pulmonary delivery of GLP-1. This is the first study focusing on the development of excipient free GLP-1 DPI formulations for inhaled therapy in Type 2 diabetes. The aerosolisation performance of both DPI formulations was studied using a next generation impactor and a DPI device (Handihaler®) at flow rate of 30 L min−1. Carriers employed were either a 10% w/w glycine-mannitol prepared by spray freeze drying or commercial mannitol. Spray freeze dried (SFD) carrier was spherical and porous whereas commercial mannitol carrier exhibited elongated particles (non-porous). GLP-1 powder without excipients for inhalation was prepared using spray drying and characterised for morphology including size, thermal behaviour, and moisture content. Spray dried (SD) GLP-1 powders showed indented/dimpled particles in the particle size range of 1–5 µm (also mass median aerodynamic diameter, MMAD: <5 µm) suitable for pulmonary delivery. Across formulations investigated, carrier-free DPI formulation showed the highest fine particle fraction (FPF: 90.73% ± 1.76%, mean ± standard deviation) and the smallest MMAD (1.96 µm ± 0.07 µm), however, low GLP-1 delivered dose (32.88% ± 7.00%, total GLP-1 deposition on throat and all impactor stages). GLP-1 delivered dose was improved by the addition of SFD 10% glycine-mannitol carrier to the DPI formulation (32.88% ± 7.00%–45.92% ± 5.84%). The results suggest that engineered carrier-based DPI formulations could be a feasible approach to enhance the delivery efficiency of GLP-1. The feasibility of systemic pulmonary delivery of SD GLP-1 for Type 2 diabetes therapy can be further investigated in animal models.

Keywords

Dry powder inhaler formulation, Glucagon-like peptide-1(7–36) amide, D-mannitol carrier, Glycine, Spray freeze drying, Spray drying

Effect of chitosan coating on the properties of nanoliposomes loaded with oyster protein hydrolysates: Stability during spray-drying and freeze-drying

Yuyang Ma, Jinjin Xu, Suisui Jiang, Mingyong Zeng

Abstract

Oyster protein hydrolysate (OPH) has high bioactivity and excellent performance, but its application in food formulation is still limited due to poor flavor and instability. In the present study, OPH was prepared by enzymatic hydrolysis and loaded into nanoliposomes. Then, the effects of chitosan coating (0, 0.25, 0.5, and 1.0%) on the physical properties, stability, and antioxidant activity were evaluated. The results showed that 1% chitosan-coated nanoliposomes had high encapsulation efficiency (EE) and physical stability. Additionally, chitosan coating slowed the release rate of nanoliposomes and increased the retention rate of antioxidant activity of OPH. The stability of the uncoated/coated nanoliposomes in a maltodextrin matrix by spray/freeze drying was evaluated. FTIR spectrum showed that hydrogen bonds, hydrophobic, and electrostatic interactions had been formed between chitosan-coated nanoliposomes and maltodextrin. Chitosan coating significantly improved the physical stability and antioxidant activity retention of nanoliposomes during powder reconstitution.

Keywords

Oyster protein hydrolysates, Nanoliposomes, Chitosan coating, Spray/freeze drying, Stabilization