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Concept: Spray drying


The aim of this study was to develop a spray dried submicrometer powder formulation suitable for the excipient enhanced growth (EEG) application. Combination particles were prepared using the Buchi Nano spray dryer B-90. A number of spray drying and formulation variables were investigated with the aims of producing dry powder formulations that were readily dispersed upon aerosolization and maximizing the fraction of submicrometer particles. Albuterol sulfate, mannitol, L-leucine, and poloxamer 188 were selected as a model drug, hygroscopic excipient, dispersibility enhancer and surfactant, respectively. Formulations were assessed by scanning electron microscopy and aerosol performance following aerosolization using an Aerolizer® dry powder inhaler (DPI). In vitro drug deposition was studied using a realistic mouth-throat (MT) model. Based on the in vitro aerosolization results, the best performing submicrometer powder formulation consisted of albuterol sulfate, mannitol, L-leucine and poloxamer 188 in a ratio of 30:48:20:2, containing 0.5% solids in a water:ethanol (80:20% v/v) solution which was spray dried at 70°C. The submicrometer particle fraction (FPF(1μm/ED)) of this final formulation was 28.3% with more than 80% of the capsule contents being emitted during aerosolization. This formulation also showed 4.1% MT deposition. The developed combination formulation delivered a powder aerosol developed for the EEG application with high dispersion efficiency and low MT deposition from a convenient DPI device platform.

Concepts: Electron, Drying, Dosage forms, Spray drying, Nano spray dryer


The present study was conducted to examine the feasibility of nimodipine loaded PLGA microparticles suspended in Tisseel(™) fibrin sealant as an in situ forming depot system. This device locally placed can be used for the treatment of vasospasm after a subarachnoid hemorrhage. Microparticles were prepared via spray drying by using the vibration mesh spray technology of Nano Spray Dryer B-90. Spherically shaped microparticles with different loadings and high encapsulation efficiencies of 93.3% to 97.8% were obtained. Depending on nimodipine loading (10% - 40%) the particle diameter ranged from 1.9 ± 1.2 μm to 2.4 ± 1.3μm. Thermal analyses using DSC revealed that Nimodipine is dissolved in the PLGA matrix. Also fluorescent dye loaded microparticles were encapsulated in Tisseel(™) to examine the homogeneity of particles. 3D-pictures of the in situ forming devices displayed uniform particle homogeneity in the sealant matrix. Drug release was examined by fluorescence spectrophotometry which demonstrated a drug release proportional to the square root of time. A prolonged drug release of 19.5 h was demonstrated under in vitro conditions. Overall, the Nimodipine in situ forming device could be a promising candidate for the local treatment of vasospasm after a subarachnoid hemorrhage.

Concepts: Scientific method, Subarachnoid hemorrhage, In vitro, In situ, Spray drying, Vasospasm, Spray nozzle, Nano spray dryer


Nanotechnology receives a widespread application in semiconductor, manufacturing, and biotechnology industries [1]. Its biggest societal impact in pharmaceutical application is related to its use in design of nanomedicine with the aim to improve medical efficacy via resolving the poor drug bioavailability status. Pharmaceutical nanoparticles can be described as solid colloidal particles with sizes below 1000 nm [1-6]. Examples of nanocarrier are liposome, cocheates, polymeric micelle, dendrimer, nanosuspension, nanoemulsion, nanosphere and nanotube [4, 7-10]. The nanoparticles can be used to deliver polypeptides, proteins, nucleic acids, genes and vaccines [3]. Active pharmaceutical ingredients can be adsorbed, encapsulated or covalently attached to the surface/into the matrix of nanoparticles [1, 11-14]. Owing to small physical size and large specific surface area, they can improve the dissolution of poorly water-soluble drugs, enhance transcytosis across epithelial and endothelial barriers, enable drug targeting, enhance bioavailability, reduce dose and associated toxicity [1, 6, 14, 15]. Nanoparticles can enhance drug stability and efficacy, and enable sustained delivery [16, 17]. They can avoid or encounter rapid clearance by phagocytes thereby leading to prolonged or reduced drug circulation in the body, as a function of particle size and surface characteristics [8, 18, 19]. The nanoparticles can penetrate cells and target organs such as liver, spleen, lung, spinal cord and lymph. Its drug targeting element is mainly exploited in the treatment of solid tumors, cardiovascular diseases, and immunological diseases [15, 20-22]. Nonetheless, manufacturing of nanomedicine can be complex and additional hurdles are expected in the development for clinical usage. Spray drying is commonly used in the pharmaceutical industry to convert a liquid phase into a dry, solid powder. Both microparticles and nanoparticles can be produced/processed by means of spray drying technology. A thorough review of patents with reference to the value of spray drying technology in nanoproduct development and commercialization has been provided by Beck et al. (2012) and Patel et al. (2014) in the late issues of Recent Patents on Drug Delivery and Formulation [23,24]. Principally, the nanoparticles are obtainable via three approaches: i) spray drying solutions to obtain nanoparticles, ii) spray drying emulsions/dispersions to obtain nanoparticles and iii) spray drying pre-formed nanoparticles. The main challenges encountered by the existing spray drying or the latest nanospray drying technology are low production throughput, long production duration, and limited flexibility in processing operation when two or more reactive substances are required to be co-sprayed in situ, use of protein drugs that are prone to be lost via adsorption onto the processing device with time, and need of complex decoration of nanoparticles to enable drug targeting are concerned. Inferring from these shortfalls, it indicates that there is still an ample room for nanospray drying technology development in order to meet the therapeutic and commercial demands of the nanomedicine.

Concepts: Pharmacology, Drug, Nanotechnology, Colloid, Pharmaceutical drug, Active ingredient, Spray drying, BET theory


Nanoenergetic formulations under flash heating: Periodate salt nanoparticles are synthesized by a facile aerosol spray drying process and demonstrate highly reactive properties as oxidizers in an aluminum-based nanoenergetic formulation. Direct evidence supports that gas phase oxygen release from the oxidizer decomposition is critical in the ignition and combustion of these formulations.

Concepts: Oxygen, Carbon dioxide, Nitrogen, Phase, Critical point, Nitric acid, Spray drying, Internal combustion engine


Dry powder inhalers (DPIs) have been proposed as an alternative administration route for protein and peptide drugs. However, DPI particles are easy to aggregate due to the strong interactions between the particles, leading to poor aerosolization performance. In this study, fragmented particles containing octreotide acetate (OA) were prepared by spray drying technique for dry powder inhalation, which were expected to decrease the particle-particle interaction by reducing the contact sites. Mannitol and ammonium carbonate were used as protein stabilizer and fragment-forming agent, respectively. The obtained fragmented particles presented larger particle size, lower density, better dispersibility, and well in vitro aerodynamic behavior (emitted dose > 97%, fine particle fraction ≈ 40%). The circular dichroism spectrum results indicated that OA maintained the stability throughout the spray drying process. The relative bioavailability of dry powder inhalation (DPI) compared with subcutaneous injection of commercial product was up to 88.0%, demonstrating the feasibility of DPI for OA delivery. These results confirmed that the proposed fragmented particles had great potential for pulmonary delivery of protein and peptide drugs in a painless, rapid, and convenient manner.

Concepts: Protein, Protein structure, Pharmacology, Particle physics, Circular dichroism, Dosage forms, Spray drying, Strong interaction


Pharmacotherapy of tuberculosis is potentially more efficient when delivered by the inhaled route than by the current oral and/or parenteral routes due to the higher concentration of drug reaching the primary region of infection in the lungs. This study investigated the influence of the amino acid L-leucine alone and in combination with the phospholipid, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), on the aerosolization behaviour of the anti-TB drugs, pyrazinamide and moxifloxacin HCl. Spray dried powders of pyrazinamide (P), moxifloxacin (M) alone and in combination with 10% L-leucine (PL and ML) and 10% DPPC (PLD and MLD) were produced. The particle sizes of all powders except P were in the inhalable size range (< 5 µm) but differ in their morphology in presence of the excipients. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed the migration of surface active L-leucine and DPPC onto the surface of the particles during the spray drying process. The aerosolization from a dry powder inhaler, Aerolizer®, using a next generation impactor revealed fine particle fraction (FPF) values for P, PL and PLD of 18.7 ± 3.4%, 53.0 ± 3.2% and 74.5 ± 5.3% respectively while FPF values for M, ML and MLD were 55.6 ± 3.3%, 74.7 ± 4.7% and 74.1 ± 1.3% respectively. In conclusion, the differences in the aerosolization behaviours of the pyrazinamide and moxifloxacin spray dried powders with and without excipients was a combination of difference in the surface morphology and surface composition.

Concepts: Electron, Spectroscopy, Amino acid, Mass spectrometry, Drying, X-ray photoelectron spectroscopy, Secondary ion mass spectrometry, Spray drying


The present study explored the potential of ternary aggregates composed of lactoferrin (LF), high methylated pectin (HMP) and EGCG in stabilizing β-carotene emulsions. Different ternary aggregates were fabricated by mixing the three components in different sequences, followed by spray drying. Fluorescence measurement and FTIR analysis indicated that ternary aggregates and LF-HMP binary complex were formed mainly through hydrogen bonding and hydrophobic interactions. The mixing sequences of three components and the spray drying process resulted in different structures of ternary aggregates. When applied to stabilizing β-carotene emulsions, ternary aggregates were effective in retarding droplet aggregation and creaming, and protecting β-carotene from degradation, compared to the binary complexes of LF, HMP or EGCG. The least loss of β-carotene was observed in the emulsions stabilized by spray-dried ternary aggregates. The conclusion obtained from the present study would be useful in the development of novel delivery systems for bioactive compounds.

Concepts: Oxygen, Hydrogen, Intermolecular forces, Covalent bond, Spray drying


This review discusses recent developments in the manufacture of inhalable dry powder formulations. Pulmonary drugs have distinct advantages compared with other drug administration routes. However, requirements of drugs properties complicate the manufacture. Control over crystallization to make particles with the desired properties in a single step is often infeasible, which calls for micronization techniques. Although spray drying produces particles in the desired size range, a stable solid state may not be attainable. Supercritical fluids may be used as a solvent or antisolvent, which significantly reduces solvent waste. Future directions include application areas such as biopharmaceuticals for dry powder inhalers and new processing strategies to improve the control over particle formation such as continuous manufacturing with in-line process analytical technologies.

Concepts: Pharmacology, Particle physics, Precipitation, Drugs, Solvent, Supercritical fluid, Phases of matter, Spray drying


In the present study, the saffron anthocyanins were encapsulated in β-glucan and β-cyclodextrin by spray drying technique to achieve their stability under adverse gastro-enviromental conditions. The microcapsules were subjected to simulated gastric conditions and release behavior of monomeric anthocyanins, antioxidants and phenols were studied. The structural properties of microcapsules were analyzed by SEM and ATR-FTIR spectroscopy. The particle size distribution, density, color, encapsulation efficiency and powder yield of samples were also evaluated. A characteristic band at 1700cm-1 by FTIR and specific enclosed particles in the cavities of wall material were observed from the micrographs of SEM that confirmed the incorporation of anthocyanins in the microcapsules. The higher content of anthocyanins, antioxidants and phenols in the intestinal conditions revealed the protection of core material from adverse conditions of stomach by encapsulation. Further studies are suggested to investigate the stability of encapsulated anthocyanins in different environmental and processing conditions.

Concepts: Nutrition, Stomach, Small intestine, Particle size distribution, Cultural studies, Digestion, Micro-encapsulation, Spray drying


An amphiphilic chitosan salt, chitosan oleate (CS-OA), was previously proposed for the physical stabilization of lemongrass antimicrobial nanoemulsions (NE) through a mild spontaneous emulsification process. As both chitosan and oleic acid are described in the literature for their positive effects in wound healing, in the present study CS-OA has been proposed to encapsulate alpha tocopherol (αTph) in NEs aimed to skin wounds. A NE formulation was developed showing about 220 nm dimensions, 36% drug loading, and αTph concentration up to 1 mg/ml. Both CS-OA and αTph NE stimulated cell proliferation on keratinocytes and fibroblast cell cultures, and in ex vivo skin biopsies, suggesting the suitability of CS-OA and of the antioxidant agent for topical application in wound healing. αTph stability, was further improved with respect of encapsulation, by spray drying the NE into a powder (up to about 90% αTph residual after 3 months). The spray drying process was optimized, to improve powder yield and αTph recovery, by a design of experiments approach. The powder obtained was easily re-suspended to deliver the NE and resulted able to completely release αTph.

Concepts: Wound healing, Antioxidant, Cell culture, Wound, Drying, Oleic acid, Spray drying, Poppyseed oil