The stability of ascorbic acid microencapsulated in granules of rice starch and in gum arabic

Ascorbic acid (AA) was microencapsulated by spray drying, using gum arabic and rice starch as covering materials. The AA was dissolved in solutions of the wall material prior to processing. For the rice starch, gelatin was used as a binding agent and recovery was effected with calcium pectate. The morphology of the materials was analysed by optical and scanning electron microscopy, it thus being possible to verify the formation and evaluate the structural characteristics of the microcapsules. The capsules produced with gum arabic were smaller (d _50% = 8:0 mum) and with a multimode particle size distribution, whilst uncovered starch capsules containing 1-2%gelatin presented a distribution mainly in the range of 5-40 mum. The capsules recovered with calcium pectate had average diameters 10-15 times greater than those obtained only by spray drying. The stability of the encapsulated materials was studied at room temperature (RH 60-65%) and at 45C (RH 60-65%and 90.7%). AA microencapsulated in gum arabic was shown to be as stable as free crystalline AA under environmental conditions, whereas that encapsulated in rice starch was less stable. Increasing the amount of the binding agent gelatin increased the stability of the uncovered starch encapsulated AA. Recovery with calcium pectate notably increased the stability of the starch encapsulated AA, as compared to the uncovered samples.     

The stability of ascorbic acid microencapsulated in granules of rice starch and in gum arabic

Ascorbic acid (AA) was microencapsulated by spray drying, using gum arabic and rice starch as covering materials. The AA was dissolved in solutions of the wall material prior to processing. For the rice starch, gelatin was used as a binding agent and recovery was effected with calcium pectate. The morphology of the materials was analysed by optical and scanning electron microscopy, it thus being possible to verify the formation and evaluate the structural characteristics of the microcapsules. The capsules produced with gum arabic were smaller (d50% = 8.0 microns) and with a multimode particle size distribution, whilst uncovered starch capsules containing 1-2% gelatin presented a distribution mainly in the range of 5-40 microns. The capsules recovered with calcium pectate had average diameters 10-15 times greater than those obtained only by spray drying. The stability of the encapsulated materials was studied at room temperature (RH 60-65%) and at 45 degrees C (RH 60-65% and 90.7%). AA microencapsulated in gum arabic was shown to be as stable as free crystalline AA under environmental conditions, whereas that encapsulated in rice starch was less stable. Increasing the amount of the binding agent gelatin increased the stability of the uncovered starch encapsulated AA. Recovery with calcium pectate notably increased the stability of the starch encapsulated AA, as compared to the uncovered samples.     

Spray dried microparticles for controlled delivery of mupirocin calcium: Process–tailored modulation of drug release

Spray dried microparticles containing mupirocin calcium were designed as acrylic matrix carriers with modulated drug release for efficient local drug delivery at minimum daily dose. Particle generation in spray drying and its effect on release performance were assessed by varying drug?:?polymer ratios with consequently altered initial saturations. Narrow-sized microparticles with mean diameters of 1.7–2.5?µm were obtained. Properties of the generated solid dispersions were examined by X-ray, thermal (thermogravimetric analysis, modulated differential scanning calorimetry) and spectroscopic (Fourier transformed infrared, Fourier transformed Raman) methods and correlated with drug loading and in vitro release. The best control over mupirocin release was achieved for 2?:?1 (w/w) drug?:?polymer ratio and found to be strongly process-dependent. For a particular ratio, increased feed concentration (>4%) boosted while increased inlet temperature (≥100°C) reduced drug release. Antimicrobial activity testing confirmed that encapsulated drug preserved its antibacterial effectiveness. Conclusively, spray drying was proven as a suitable method for preparing structured microparticles which can control drug release even at exceptionally high drug loadings.     

Solubility enhancement of a poorly water-soluble anti-malarial drug: experimental design and use of a modified multifluid nozzle pilot spray drier

A modified multifluid nozzle spray drier was used to prepare drug containing microparticles of a poorly water-soluble anti-malarial drug, artemisinin (ART) with the aim of improving its solubility. We investigated the spray drying of ART with maltodextrin (MD) via a full factorial experimental design considering the effect of drying temperature, feed ratio (ART:MD), feed flow rate and pressure on the physical properties and solubility of spray-dried ART. Characterization of the ART powder, spray-dried ART microparticles and spray-dried ART-MD were analyzed by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD) and solubility. DSC and XRD studies suggested that the crystallinity of spray-dried particles was decreased with increasing inlet temperatures and flow rate. The particle size of spray-dried ART microparticles was found to be dependent on inlet temperature, flow rate, pressure and feed ratio. The solubility of spray-dried ART particles in composites was markedly increased as compared to commercial ART. A solubility surface-response model was regressed and statistically assessed before elucidating the significant and direct relationships between inlet temperature and feed rate on one hand and solubility on the other. An optimal pressure condition was observed while feed ratio had relatively reduced effect on solubility. The model was also used in an optimization exercise identifying the optimal solubility to be 66.2 +/- 7.17 microg/mL under the calculated spray drying conditions of: inlet temperature = 140 degrees C, feed ratio (ART:MD) = 0.1, feed flow rate = 250 mL h(-1), and pressure = 1.38 bar.     

Preparation and characterisation of novel spray-dried nano-structured para-aminosalicylic acid particulates for pulmonary delivery: impact of ammonium carbonate on morphology, chemical composition and solid state

Objectives The objective of this work was to spray dry p‐aminosalicylic acid (PAS) and its ammonium salt and to investigate the impact of the pore‐forming agent, ammonium carbonate (AC), on the morphological, aerodynamic and physicochemical properties of the resulting powders. Methods Microparticles were prepared by spray drying from ethanol/water solvent systems. Their solid‐state properties were evaluated by scanning electron microscopy, powder X‐ray diffraction, differential scanning calorimetry, thermogravimetric analysis and in‐vitro deposition, using the twin impinger. Key Findings The physicochemical properties of PAS were altered on spray drying with AC and a new solid state was produced. The solution composition impacted on the morphology of the resulting powders, which ranged from irregular crystal agglomerates to spherical crystal clusters and porous microparticles. The chemical composition, structure and morphology were dependent on process inlet temperature, low inlet temperatures resulting in a novel solid of stoichiometry; PAS : ammonia : water, 2 : 1 : 0.5. At higher temperatures pure PAS was obtained. In‐vitro deposition studies showed an increase in emitted dose from spray dried drug, relative to the micronised PAS. Conclusions Under appropriate process conditions AC interacts with the acidic PAS, resulting in the formation of a novel solid‐state drug phase. Spray‐dried PAS powders have potential for pulmonary delivery.     

Survival of Beijerinckia sp. microencapsulated in carbohydrates by spray-drying

The encapsulation of Beijerinckia sp. cell suspension in different wall materials using the spray drying technique was performed. Mat dextrin, dehydrated glucose syrups, gum acacia and modified starch materials were tested. Cell viability assays were carried out before and after drying and during storage of the products. The surface area and characteristics of the encapsulated powders were examined using BET adsorption of N₂ and scanning electron microscopy, respectively. The residual moisture content and water activity of the powders were also determined. The best results were obtained with the dehydrated glucose syrup, which resulted in products with the greatest per cent survival during the drying process and subsequent storage period. The products obtained with the dehydrated glucose syrup showed more uniform microcapsule surfaces at lower A_w values and residual moisture content.     

Microencapsulation of insulin using a W/O/W double emulsion followed by complex coacervation to provide protection in the gastrointestinal tract

Abstract

Microcapsules containing insulin were prepared using a combination of a W/O/W double emulsion and complex coacervation between WPI (used as a hydrophilic emulsifier) and CMC or SA with further spray drying of the microcapsules in order to provide protection in the gastrointestinal tract. The microcapsules prepared exhibited high encapsulation efficiency and showed the typical structure of a double emulsion. After spray drying of these microcapsules, the integrity of the W/O/W double emulsion was maintained and the biological residual activity remained high when using the combination of 180?°C inlet air temperature and 70?°C outlet air temperature. The microcapsules exhibited low solubility at pH 2 and high solubility at pH 7 so they might protect insulin at acid pH values in the stomach and release it at intestinal pH values. The microcapsules developed in this study seem to be a promising oral delivery vehicle for insulin or other therapeutic proteins.     

Ternary Phase Diagram Development and Production of Niclosamide-Urea Co-Crystal by Spray Drying

In this work, a ternary phase diagram was developed for a Niclosamide-urea co-crystal (NCS-UR) in isopropanol (IPA) using a combination of slurry and solvent addition methods. The ternary phase diagram showed that solubility of Niclosamide and urea differed by an order of magnitude in IPA, leading to an incongruently saturating system. Spray drying was explored as a method to generate NCS-UR. Co-crystals with small, uniform particle size were successfully prepared by spray drying from equimolar solutions with yield up to 73%. Co-crystals were phase pure by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) from all conditions explored. Somewhat similar particles were obtained at inlet temperature of 70 °C (mean size of 2.0 μm) compared to 85 °C (2.8–3.4 μm). Based on the TPD, isolating phase pure co-crystal through solution crystallization in IPA would require excess urea. However, spray drying did not require excess co-former. The in-vitro solubility of NCS-UR was compared to anhydrous NCS in biorelevant media. NCS-UR did not give improvement in solubility at 1 h or 24 h. Overall, this work showed that spray drying is a feasible process for preparing phase pure co-crystals for an incongruently saturating system and simultaneously generating micron size particles.     

Soy extract and maltodextrin as microencapsulating agents for Lactobacillus acidophilus: a model approach

Abstract

The present study aimed to optimise the microencapsulation of Lactobacillus acidophilus La-05 by spray drying, using soy extract and maltodextrin as encapsulants. Air inlet temperature, maltodextrin/soy extract ratio and feed flow rate were investigated through Central Composite Rotational Design (CCRD). Probiotic viability increased with increasing the proportion of soy extract. Temperature and feed flow rate had a negative effect. Particle diameter ranged from 4.97 to 8.82?μm, water activity from 0.25 to 0.52 and moisture from 2.30 to 7.01?g.100g^?1 Particles produced following the optimised conditions (air temperature of 87?°C, maltodextrin/soy extract ratio of 2:3 w.w^?1, feed flow rate of 0.54?L.h^?1) reached Encapsulation yield (EY) of 83%. Thermogravimetry and FTIR analysis suggested that microcapsules could protect L. acidophilus cells against dehydration and heating. During storage, microencapsulated probiotic had high cell viability (reductions ranged between 0.12 and 1.72 log cycles). Soy extract/maltodextrin presented well-encapsulating properties of Lactobacillus acidophilus La-05.     

Impact of process variables on the micromeritic and physicochemical properties of spray‐dried microparticles – Part II. Physicochemical characterisation of spray‐dried materials

Objectives In this work we investigated the residual organic solvent content and physicochemical properties of spray‐dried chlorothiazide sodium (CTZNa) and potassium (CTZK) salts. Methods The powders were characterised by thermal, X‐ray diffraction, infrared and dynamic vapour sorption (DVS) analyses. Solvent levels were investigated by Karl–Fischer titration and gas chromatography. Key findings Spray‐drying from water, methanol (MeOH) and mixes of MeOH and butyl acetate (BA) resulted in amorphous microparticles. The glass transition temperatures of CTZNa and CTZK were ～192 and ～159°C, respectively. These materials retained their amorphous nature when stored at 25°C in dry conditions for at least 6 months with no chemical decomposition observed. DVS determined the critical relative humidity of recrystallisation of CTZNa and CTZK to be 57% RH and 58% RH, respectively. The inlet temperature dependant oxidation of MeOH to formaldehyde was observed; the formaldehyde was seen to deposit within the amorphous matrix of spray‐dried product. Spray‐drying in the open blowing mode coupled with secondary drying resulted in a three‐fold reduction in residual BA (below pharmacopoeial permitted daily exposure limit) compared to spray‐drying in the closed mode. Conclusions Experiments showed that recirculation of recovered drying gas increases the risk of deposition of residual solvents in the spray‐dried product.     

Spray drying from organic solvents to prepare nanoporous/nanoparticulate microparticles of protein: excipient composites designed for oral inhalation

Objectives The aim of this study was to determine if spray‐drying could successfully produce microparticles containing the model protein trypsin in a form suitable for inhalation. Methods Trypsin was spray‐dried with raffinose from a methanol : n‐butyl acetate solvent system (MeOH : BA). The solvent system was then adjusted to include water, and trypsin was co‐spray‐dried with raffinose, trehalose or hydroxpropyl‐β‐cyclodextrin. The spray‐dried products were characterised by SEM, XRD, DSC, TGA and FTIR. Protein biological activity and in‐vitro deposition of trypsin : excipient nanoporous/nanoparticulate microparticles (NPMPs) was also assessed. Key findings The inclusion of water in a MeOH : BA solvent system allowed for the successful production of NPMPs of trypsin : excipient by spray‐drying. Trypsin formulated as trypsin : excipient NPMPs retained biological activity on processing and showed no deterioration in activity or morphological characteristics when stored with desiccant at either 4 or 25°C. Hydroxpropyl‐β‐cyclodextrin showed advantages over the sugars in terms of producing powders with appropriate density and with greater physical stability under high‐humidity conditions. Fine particle fractions of between 41 and 45% were determined for trypsin : excipient NPMPs. Conclusions NPMPs of trypsin : excipient systems can be produced by spray‐drying by adjustment of the solvent system to allow for adequate solubility of trypsin.     

Microencapsulation of cocoa liquor nanoemulsion with whey protein using spray drying to protection of volatile compounds and antioxidant capacity

Abstract

The aim of this study was microencapsulated a nanoemulsion of cocoa liquor with whey protein by spray drying, and evaluate the effect of different inlet drying temperatures on the properties of microcapsules. The nanoemulsion showed a particle size of 202.13?nm, PdI of 0.424, and ζ-potential of ?25.20?mV. The inlet drying temperature showed differences in physicochemical properties of microcapsules. Microcapsules presented good thermal stability and protection against the melting of cocoa liquor. Microcapsules obtained showed excellent yields of polyphenolic compounds (78–93%), and high retention of volatile compounds, especially of pyrazines. Greater microencapsulation yield of bioactive compounds and retention of volatile compounds was obtained at higher drying temperature (180?°C). Excellent stability of polyphenols content, antioxidant capacity, and volatile compounds of cocoa liquor were observed during storage of the microcapsules at different temperature conditions, indicating the feasibility of this powder for its incorporation into functional foods.     

Effects of lipid formulations on clove extract spray dried powders: comparison of physicochemical properties,storage stability and in vitro intestinal permeation

Abstract

Clove is an aromatic plant spice with potent antioxidant and anti-inflammatory activity. Eugenol is the main compound which contributes to such medicinal and nutritional benefits. To date, the formulation of unstable, volatile and poorly water-soluble compounds remains a challenging task. Lipid formulations can be used to improve physicochemical and biopharmaceutical properties of poorly soluble compounds. The aim of this study is to investigate the effects of lipids, such as Gelucire and Compritol on physicochemical properties; stability and in vitro intestinal permeation of spray dried powdered formulations loaded with clove’s bioactive compounds. Results showed that eugenol retention in spray-dried powders could be correlated with antioxidant activity and with mass recovery after spray drying. Adding Gelucire but not Compritol to clove extract formulations, improved solubility of spray dried powders. Stability test in high humidity environment (63.5% RH) suggested that formulations including both Gelucire and Compritol were significantly more stable compared to the formulation without any lipid at the two tested temperatures (25?°C and 40?°C). This suggests that lipid additions to clove (Syzygium aromaticum) extract formulations provide protective effects for the spray dried powders in high-humidity environments. In addition, results from in vitro intestinal permeation studies suggested that eugenol uptake, was not being hindered by transporters nor was the absorption being affected by lipid formulations.     

Aerosol Delivery of Nanoparticles in Uniform Mannitol Carriers Formulated by Ultrasonic Spray Freeze Drying

Purpose

While most examples of nanoparticle therapeutics have involved parenteral or IV administration, pulmonary delivery is an attractive alternative, especially to target and treat local infections and diseases of the lungs. We describe a successful dry powder formulation which is capable of delivering nanoparticles to the lungs with good aerosolization properties, high loadings of nanoparticles, and limited irreversible aggregation.

Methods

Aerosolizable mannitol carrier particles that encapsulate nanoparticles with dense PEG coatings were prepared by a combination of ultrasonic atomization and spray freeze drying. This process was contrasted to particle formation by conventional spray drying.

Results

Spray freeze drying a solution of nanoparticles and mannitol (2 wt% solids) resulted in particles with an average diameter of 21?±?1.7 μm, regardless of the fraction of nanoparticles loaded (0–50% of total solids). Spray freeze dried (SFD) powders with a 50% nanoparticle loading had a fine particle fraction (FPF) of 60%. After formulation in a mannitol matrix, nanoparticles redispersed in water to < 1 μm with hand agitation and to < 250 nm with the aid of sonication. Powder production by spray drying was less successful, with low powder yields and extensive, irreversible aggregation of nanoparticles evident upon rehydration.

Conclusions

This study reveals the unique advantages of processing by ultrasonic spray freeze drying to produce aerosol dry powders with controlled properties for the delivery of therapeutic nanoparticles to the lungs.     

Nano spray drying: a novel method for preparing protein nanoparticles for protein therapy

There has been an increasing interest in the development of protein nanotherapeutics for diseases such as cancer, diabetes and asthma. Spray drying with prior micro mixing is commonly used to obtain these powders. However, the separation and collection of protein nanoparticles with conventional spray dryer setups has been known to be extremely challenging due to its typical low collection efficiency for fine particles less than 2μm. To date, there has been no feasible approach to produce these protein nanoparticles in a single step and with high yield (>70%). In this study, we explored the feasibility of the novel Nano Spray Dryer B-90 (equipped with a vibrating mesh spray technology and an electrostatic particle collector) for the production of bovine serum albumin (BSA) nanoparticles. A statistical experimental design method (Taguchi method based on three levels, five variables L(18) orthogonal array robust design) was implemented to study the effect of and optimize the experimental conditions of: (1) spray mesh size, (2) BSA solution concentration, (3) surfactant concentration, (4) drying air flow rate and (5) inlet temperature on: (1) size and (2) morphology (axial ratio). Particle size and morphology were predominantly influenced by the spray mesh size and surfactant concentration, respectively. The drying air flow rate and inlet temperature had minimal impact. Optimized production of smooth spherical nanoparticles (median size: 460±10nm, axial ratio: 1.03±0.00, span 1.03±0.03, yield: 72±4%) was achieved using the 4μm spray mesh at BSA concentration of 0.1% (w/v), surfactant concentration of 0.05% (w/v), drying flow rate of 150L/min and inlet temperature of 120°C. The Nano Spray Dryer B-90 thus offers a new, simple and alternative approach for the production of protein nanoparticles suited for a variety of drug delivery applications.     

Spray-dried insulin particles retain biological activity in rapid in-vitro assay.

The purpose of this study was to rapidly determine, without the use of extensive animal studies, whether biological activity is retained after spray drying insulin with two excipients, lactose and xanthan gum. This was achieved by the detection of protein kinase B (PKB), which is activated by phosphorylation in response to insulin binding to cellular receptors. A myeloid cell line was cultured and stimulated with the reconstituted insulin powders. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was then utilised to allow in-vitro detection of phosphorylated PKB using an anti-phospho-PKB antibody. A single band specific to phosphorylated PKB was found on the Western blots, indicating that the active conformation of insulin was retained when spray dried in combination with lactose and with xanthan gum over the spray-drying inlet temperature range of 110-170 degrees C. Evidence of inactivation/denaturation was observed when insulin was spray dried at an inlet temperature of 200 degrees C. The assay may be of use as a more rapid and economic means to screen insulin formulations for inhalation and other purposes as opposed to conventional monitoring of blood glucose levels in animals.     

Survival of Beijerinckia sp. microencapsulated in carbohydrates by spray-drying

The encapsulation of Beijerinckia sp. cell suspension in different wall materials using the spray drying technique was performed. Mat dextrin, dehydrated glucose syrups, gum acacia and modified starch materials were tested. Cell viability assays were carried out before and after drying and during storage of the products. The surface area and characteristics of the encapsulated powders were examined using BET adsorption of N(2) and scanning electron microscopy, respectively. The residual moisture content and water activity of the powders were also determined. The best results were obtained with the dehydrated glucose syrup, which resulted in products with the greatest per cent survival during the drying process and subsequent storage period. The products obtained with the dehydrated glucose syrup showed more uniform microcapsule surfaces at lower A(w) values and residual moisture content.     

Beauveria brongniartii subjected to spray-drying in a composite carrier matrix system

The negative aspects of chemical pesticides are of growing concern to the public. Thus, there is a strong effort to exploit environmentally friendly possibilities for pest management. One strategy is the application of biocontrol agents such as the fungus Beauveria brongniartii. In this context, the central objective of the research presently described is to investigate spray drying as a preservation method for fungal conidia to obtain a practical formulation for spray application. An aqueous binary mixture composed of skim milk (SM) and polyvinylpyrrolidone (PVP K90) was examined as encapsulation matrix. The influence of different inlet/outlet temperature adjustments, the composition of the carrier system and the conidia concentration were examined with respect to their influence on spore viability. Results indicate that air outlet temperatures up to 53 ± 2°C resulted in a slight reduction of conidial viability (≈3%). Microencapsulated conidia have been subjected to storage tests with and without the addition of silica gel capsules at various temperatures. Results show that survival is inversely related to storage temperatures and residual moisture levels of the spray dried powders. The highest survival rates were observed at moisture contents of 3% and a temperature of 10°C. Moreover, production characteristics like entrapment efficacy, shape and size were investigated. Furthermore, the composition of the carrier matrix was optimised to result in production yields of 25%. Results show that spray drying is a useful, economic encapsulation technology for aerial conidia of Beauveria brongniartii resulting in highly concentrated, spray dried powders of 92% viability.     

Microencapsulation of an indigenous isolate of Bacillus thuringiensis by spray drying

In this study, microencapsulation by spray drying was performed to protect spores and crystals of an indigenous isolate of Bacillus thuringiensis Se13 from environmental stress. The effects of wall material, inlet temperature, and outlet temperature on microencapsulation of Bt-Se13 were investigated using Taguchi’s orthogonal array. The most suitable wall material determined as maltodextrin DE10. The optimum inlet and outlet temperatures of spray drier were determined as 160?°C and 70?°C, respectively. The number of viable spores, mean particle size, wetting time, percentage of suspensibility and moisture content of the product produced under optimum conditions were determined as 8.1?×?10¹¹ cfu g^?1, 13.462?µm, 25.22?s, 77.66% and 7.29%, respectively. As a result of efficiency studies on Spodoptera exigua in the laboratory conditions, the LC₅₀ was determined as 1.6?×?10⁴ cfu mL^?1. Microencapsulated Bt-Se13 based bio-pesticide may be registered for the control of S. exigua and can be tested against other lepidopterans which share the same environment.     

螺旋霉素超细粉的喷干法和反溶剂法制备及性质研究

摘要：目的 螺旋霉素原料药粉的粒径大、团聚现象严重,因此极大的限制了其临床应用;有研究报道超细粉制备技术可 以很好地解决这些问题; 方法 采用了两种代表性的方法制备螺旋霉素的超细粉：分别为喷雾干燥法和反溶剂法;并以粒径为 指标,采用单因素实验优化得到最佳结果,对上述两种方法制备的粉体分别进行粒径、形貌特征和物化性质对比。结果 两种 方法的最佳条件为：喷雾干燥法的进料速度为5 mL/min,雾化空气速度为800 L/h,进口温度为150℃,出口温度为85℃,平均 粒径为(1638±10.99) nm。反溶剂法在25℃条件进行实验,溶剂与反溶剂的比例为1:5,最佳搅拌速度为1000 r/min,获得的平均 粒径为(230±7.31)nm,以上结果经过扫描电子显微镜(SEM),动态光散射(DLS),傅立叶变换红外光谱(FTIR),差示扫描量热仪 (DSC)和X射线衍射(XRD)进行表征;经气相色谱检测,两种方法中的溶剂残留均符合ICH最低标准(5000 ppm);结论 与喷雾干 燥法相比,反溶剂法制备的螺旋霉素粒径更小、粉体分散性更佳,其溶解度更高。因此反溶剂法制备的螺旋酶素微粉更适用于 制药业,为微粉技术提供技术思路。