Formulation and optimization of sildenafil citrate-loaded PLGA large porous microparticles using spray freeze-drying technique: A factorial design and in-vivo pharmacokinetic study

Formulation and optimization of sildenafil citrate-loaded PLGA large porous microparticles using spray freeze-drying technique: A factorial design and in-vivo pharmacokinetic study

Hend Shahin, Bhavani Prasad Vinjamuri, Azza A.Mahmoud, Suzan M.Mansour, Mahavir Bhupal Chougule, Lipika Chablani

Abstract

The oral administration of sildenafil citrate (SC) for the treatment of pulmonary arterial hypertension is associated with several drawbacks. The study aimed to design and formulate SC-loaded inhalable poly (lactic-co-glycolic acid) [PLGA] large porous microparticles (LPMs) for pulmonary delivery. A factorial design was used to study the effect of the composition of LPMs on physicochemical properties. The study also evaluated the effect of glucose and L-leucine concentration on the formulation. The developed LPMs demonstrated an acceptable yield% (≤48%), large geometric particle size (>5µm) with a spherical and porous surface, and sustained drug release (up to 48 h). Increasing the concentration of poly(ethyleneimine) from 0.5% to 1% in SC-loaded LPMs led to an increase in entrapment efficiency from ~3.02% to ~94.48%. The optimum LPMs showed adequate aerodynamic properties with a 97.68 ± 1.07% recovery, 25.33 ± 3.32% fine particle fraction, and low cytotoxicity. Intratracheal administration of LPMs demonstrated significantly higher lung deposition, systemic bioavailability, and longer retention time (p < 0.05) compared to orally administered Viagra® tablets. The study concluded that SC-loaded LPMs could provide better therapeutic efficacy, reduced dosing frequency, and enhanced patient compliance.

Keywords

Sildenafil citrate, Large porous microparticles, Spray-freeze drying, Pulmonary arterial hypertension, Pulmonary drug delivery, Inhalable dry powder, Design of experiment

The application of freeze-drying as a production method of drug nanocrystals and solid dispersions – A review

The application of freeze-drying as a production method of drug nanocrystals and solid dispersions – A review

Emilia Jakubowska, Janina Lulek

Abstract

This work reviews the examples of the application of lyophilization and its cryogenic modifications as the production method of solid dispersions and drug nanocrystals, two formulation approaches aimed at increasing the solubility, dissolution rate and oral bioavailability of poorly water soluble drugs. A brief recapitulation of freeze-drying basics is presented and the review is organized according to application and product type, with the consideration of different cryogenic techniques, e.g. spray freezing into liquid, as well as the combinations of lyophilization with other nanonization methods in pharmaceutical technology. The review focuses on freeze-drying as a particle engineering tool for the size reduction and surface area enhancement in the generation of nanosized drug particles, both as simple nanocrystals and as their dispersions within water soluble micro- or nanoparticulate matrices, instead of the use of lyophilization as a mere drying or solidification method. Therefore, attention is given to the relationships between formulation and process parameters (e.g. freezing rate), and the properties of the obtained material: particle size, porosity, surface area, morphology, polymorphism and dissolution behavior.

Keywords

Lyophilization, Freeze-drying, Nanocrystals, Solid dispersions, Nanonization

Influence of three types of freezing methods on physicochemical properties and digestibility of starch in frozen unfermented dough

Influence of three types of freezing methods on physicochemical properties and digestibility of starch in frozen unfermented dough

Yong Yang, Shuaishuai Zheng, Zhen Li, Zhili Pan, Zhongmin Huang, Jianzhong Zhao, Zhilu Ai

Abstract

Three types of freezing methods, namely, spiral tunnel freezing method (SF), cryogenic refrigerator freezing method (RF) and liquid nitrogen spray freezing method (LF), were applied to frozen unfermented dough. The particle size distribution and SEM results showed freezing methods reduced the average particle size of starch granules and destroyed the surface microstructure, especially RF, and the damaged starch content and swelling power of starch after treatment increased. Gelatinization and pasting properties of starches changed to varying degrees, indicating freezing methods caused the internal rearrangement of starch molecules. This view could also be inferred from X-ray diffraction (XRD) and Fourier Transform infrared spectroscopy (FT-IR) data. The relative crystallinity (35.51%–38.56%) and the R1047/1022 (0.562–0.590) were increased, compared with the control (32.44%, 0.559, respectively). Meanwhile, freezing treatment improved the digestibility of starch by promoting the combination of enzymes and starch, especially RF. Larger ice crystals formed by RF with slower freezing rate produced larger damage to starch structure, more likely to promote the binding with enzymes. LF with faster freezing rate had less effect on the starch composition than RF and SF with slower freezing rate. The data obtained clarified the influence of freezing methods on the structure and properties of starch in a yeast-free dough system, and enriched the knowledge regarding the effect of freezing technology on food components.

Keywords

Freezing methods, Frozen unfermented dough, Starch digestibility, Ordered structure, Relative crystallinity

Fabrication and microstructure analysis of continuous C fibers reinforced SiC-Cnfs hybrid composite tubes

Fabrication and microstructure analysis of continuous C fibers reinforced SiC-Cnfs hybrid composite tubes

Shaik Mubina, M. Ilaiyaraja, Asit Kumar Khanra, Bhaskar Prasad Saha

Abstract

The carbon nanofibers (Cnfs) dispersed SiC-Cnfs composite powder has been produced by spray freeze-granulation technique. SiC-based hybrid composite tubes (BN-Cf/SiC-Cnfs) were fabricated by systematically laying of boron nitride-coated continuous carbon fiber (BN-Cf) in the SiC-Cnfs composite matrix. High-density hybrid composite tubes were processed by cold isostatically pressing (CIP) of the afore-mentioned powder in a specially designed mold followed by pressureless sintering. The detailed processing techniques highlighting the criticality of each processing-step have been discussed. The implication of the processing techniques on the structure and properties of the composites were analyzed by using SEM, FTIR, and XRD, highlighting the matrix microstructure and the interfacial bonding of fiber with the matrix. In addition, the influence of newly evolved secondary-phases, Cnfs dispersion, long Cf reinforcement on optimization of properties of the hybrid composites was discussed in detail highlighting TEM analysis. The fractographic analysis of the hybrid composite tubes was carried out to understand the influence of long fibers on the improvement of fracture toughness of the nanofibers containing hybrid composite matrix. The fracture toughness and the other mechanical properties of the base matrix were found to improve significantly due to the combined contribution of specially laid long fibers in nanofibers containing matrix.

Keywords

BN-coated long C fibers, SiC-Cnfs powder, hybrid composite tubes, CIP, pressureless sintering

Stability of Instant Coffee Foam by Nanobubbles Using Spray-Freeze Drying Technique

Stability of Instant Coffee Foam by Nanobubbles Using Spray-Freeze Drying Technique

Abstract

Instant coffee with stable foam is considered to be an important parameter for consumer preference and acceptability. For foam sustenance, nanoscale bubbles are more useful compared with microbubbles, due to their high specific area and high stagnation in the liquid phase (without undesirable liquid drainage). The technique that produces nanobubbles in coffee would concomitantly produce and preserve the coffee foam, the best. Spray-freeze drying (SFD) is known to be more effective for the production of instant coffee, compared with conventional spray drying (SD) and freeze drying (FD) techniques. However, its efficiency in the production of nanobubbles has not been explored. To address the issue, in the present study, SFD has been employed to produce instant coffee, and the findings have been compared with SD and FD. The coffee powder obtained with SFD produced a foam with higher stability that also comprised of nanobubbles, in contrast to SD and FD powders. The FE-SEM analysis of SFD foam showed the presence of nanobubbles in the range of 100–200 nm. When the beverage was prepared, the SFD coffee powder dissolved in water at 90 °C produced an excellent foam. The said foam structure was intact up to 2400 s (40 min), and lost only 89.5 ± 2 mm of foam height, during the experiment. Thus, apart from instant coffee, a stable foam in coffee comprising nanobubbles can also be achieved through the SFD.

Keywords

Spray-freeze drying, Nanobubbles, Coffee, Foam stability, Foam structure

Desalination of seawater by spray freezing in a natural draft tower

Desalination of seawater by spray freezing in a natural draft tower

YangLiu, TingzhenMing, YongjiaWu, Renaudde Richter, YuepingFang, NanZhou

Abstract

The freeze-melting process can be a viable method for the purposes of desalination because of its low energy consumption, ignorable corrosion issues, and without huge pressure or membrane replacement work. Large contact area for heat and mass transfer per unit mass of water between the water and air and low heat resistance results in higher energy efficiency during spray freezing desalination process compared to other freezing desalination methods. A 200 m high desalination tower was proposed in this paper that could generate 27.7 kg/s fresh water in the form of water droplets with 2 mm diameter at an atmospheric temperature of −26°C. This research has founded that the natural convective airflow induced by the heat released by the warm water in the freezing process could generate through the wind turbine mounted in this system approximately one-third of the energy consumed by the water pump of the system. This free energy has never been studied in previous research. The power consumption required to produce 1 m3 fresh water in this system is approximately 1.07 kWh. Compared to traditional desalination methods, the power consumption of our new spray freezing desalination system is much lower than previous systems with the same mass flow rate of fresh water. Only 375.4 kJ cold energy to produce one-kilogram fresh water. Thus, this spray freezing desalination system could be employed in desalination industry if free cold energy (e.g. from the cold atmosphere or the regasification process of LNG) and seawater resources are available.

Keywords

Compressible airflowNatural draft towerSeawater desalinationSpray freezingWater droplet

Sintering investigations of a UO2-PuO2 powder synthesized using the freeze-granulation route

Sintering investigations of a UO2-PuO2 powder synthesized using the freeze-granulation route

Marion Le Guellec, Florent Lebreton, Laure Ramond, Abibatou Ndiaye, Thierry Gervais, Guillaume Bernard-Granger

Abstract

Sintering investigations of a UO2-PuO2 powder, integrating 11 wt% of PuO2 and synthesized by freeze-granulation, were completed at temperatures up to 1700°C, in an atmosphere of Ar/4 vol% H2 and 1200 vpm H2O. Analyzing the “grain size versus relative density” trajectory enabled to propose that densification was controlled by volume diffusion and grain growth by the grain boundaries. An activation energy around 630 kJ/mol was obtained for densification, which was close to the value reported for volume diffusion of plutonium cations in U1-xPuxO2 polycrystals. The sintered microstructure appeared homogeneous regarding the plutonium and uranium cations distribution.

Keywords

Sintering, Ceramics, Oxides, Microstructure, MOX

Physicochemical changes of MTGase cross-linked surimi gels subjected to liquid nitrogen spray freezing

Physicochemical changes of MTGase cross-linked surimi gels subjected to liquid nitrogen spray freezing

Xiaoying Luo, Jinling Li, Wenli Yan, Ru Liu, Tao Yin, Juan You, Hongying Du, Shanbai Xiong, Yang Hu

Abstract

Physicochemical properties of microbial transglutaminase (MTGase) cross-linked surimi gels subjected to liquid nitrogen (LN) spray freezing with different temperatures and cross-linking degrees were investigated. Gels with lower LN spray temperature (−90 °C) were found taking less time in cooling down themselves to maximum-ice-crystal generating temperature. Microstructure images showed the pores of gels became smaller and the structure gradually became denser, as freezing temperature decreased and cross-linking degree increased. It also revealed T22 relaxation time of gels decreased significantly with surimi gels cross-linking degree increasing, indicating the binding ability of gels to moisture was enhanced accordingly. Meanwhile, the proton density weighted image brightness declined along with the LN spray temperature decreasing, and the image brightness showed a decreasing trend from outside to inside, indicating that water migrated and permeated easier from the inside of the gel network to the outside undergone higher LN temperature and lower cross-linking degree. Besides, the L and W values of LN groups decreased along with LN spray temperature and cross-linking degree increasing. Moreover, −90 °C LN group with 46.70% cross-linking degree presented the highest breaking force which ascribed to their synergistic efforts in maintaining a stable and dense structure of gels via controlling ice crystals and cross-linkages’ generation.

Keywords

Surimi gel, Cross-linking degree, Liquid nitrogen spray freezing

Effect of formulation and inhaler parameters on the dispersion of spray freeze dried voriconazole particles

Effect of formulation and inhaler parameters on the dispersion of spray freeze dried voriconazole particles

Qiuying Liao, Ivan C.H. Lam, Hinson H.S. Lin, Leon T.L. Wan, Jason C.K. Lo, Waiting Tai, Philip C.L. Kwok, Jenny K.W. Lam

Abstract

Spray freeze drying is a particle engineering technique that allows the production of porous particles of low density with excellent aerosol performance for inhalation. There are a number of operating parameters that can be manipulated in order to optimise the powder properties. In this study, a two-fluid nozzle was used to prepare spray freeze dried formulation of voriconazole, a triazole antifungal agent for the treatment of pulmonary aspergillosis. A full factorial design approach was adopted to explore the effects of drug concentration, atomisation gas flow rate and primary drying temperature. The aerosol performance of the spray freeze dried powder was evaluated using the next generation impactor (NGI) operated with different inhaler devices and flow rates. The results showed that the primary drying temperature played an important role in determining the aerosol properties of the powder. In general, the higher the primary drying temperature, the lower the emitted fraction (EF) and the higher the fine particle fraction (FPF). Formulations that contained the highest voriconazole concentration (80% w/w) and prepared at a high primary drying temperature (−10 °C) exhibited the best aerosol performance under different experimental conditions. The high concentration of the hydrophobic voriconazole reduced surface energy and cohesion, hence better powder dispersibility. The powders produced with higher primary drying temperature had a smaller particle size after dispersion and improved aerosol property, possibly due to the faster sublimation rate in the freeze-drying step that led to the formation of less aggregating or more fragile particles. Moreover, Breezhaler®, which has a low intrinsic resistance, was able to generate the best aerosol performance of the spray freeze dried voriconazole powders in terms of FPF.

Keywords

Aerosol performance, Antifungal agent, Factorial design, Freeze drying, Inhalation, Pulmonary delivery, Spray freeze drying

Evaluation of Process Conditions for Ultrasonic Spray-Freeze Drying of Transglutaminase

Evaluation of Process Conditions for Ultrasonic Spray-Freeze Drying of Transglutaminase

Hilal İşleroğlu, Izzet Turker

Abstract

In this study, a commercial transglutaminase enzyme was dried using an ultrasonic spray freeze drying method and the effects of the process conditions were optimized to maximize the final transglutaminase activity. Accordingly, process parameters affecting enzyme activity were selected, such as nozzle frequency (48 and 120 kHz), flow rate (2, 5 and 8 mL/min) and plate temperature for secondary drying (25, 35 and 45 °C). Moreover, the effects of different pH values (pH=2.0 and 9.0) and high temperature (80 °C) on enzyme activity, physical properties and particle morphology of transglutaminase were discussed. According to the results, transglutaminase preserved its activity despite ultrasonic spray freeze drying. Sonication enhanced the enzyme activity. Using the desirability function method, the optimum process conditions were determined to be flow rate 3.10 mL/min, plate temperature 45 °C and nozzle frequency 120 kHz. The predicted activity ratio was 1.17, and experimentally obtained ratio was 1.14±0.02. Furthermore, enzyme produced by ultrasonic spray freeze drying had low moisture values (2.92-4.36 %) at 8 h of drying. When the morphological structure of the transglutaminase particles produced by ultrasonic spray freeze drying under the optimum conditions was examined, spherical particles with pores on their surfaces were observed. In addition, flow properties of the transglutaminase powders were considered as fair under most conditions according to the Carr index.