Spray-dried Particles Research Articles

High Resolution Nanoscale Probing of Bacteriophages in an Inhalable Dry Powder Formulation for Pulmonary Infections.

Use of powder phage formulations for the treatment of multiple-drug-resistant pulmonary infections is gaining attention. To achieve therapeutic benefits, it is critical for phages to remain stable in the formulation. Assessment of phage stability relies on plaque assay (bioactivity), which requires powder samples to be reconstituted in liquid. The purpose of this study was to develop an innovative approach using photothermal-induced resonance-enhanced atomic force microscopy infrared spectroscopy (AFM-IR) to assess the presence of phages and investigate their protein conformation in the solid state. Staphylococcal phage S83 was spray-dried with lactose and sodium stearate using spray-drying. The phage powder recrystallized at 60% relative humidity (RH), so it was stored and handled below this RH. For the AFM-IR measurements, spray-dried Staphylococcal phage Sa83 powder was embedded in resin, followed by microtome sectioning. AFM-IR spectra collected from different regions within the microtomed sections revealed the presence of phage proteins with amide I and amide II bands at 1640 and 1550 cm-1, respectively. The phages were confirmed to be stable, as the plaque assay showed negligible titer reduction after spray-drying. Our results thus demonstrated the utility of AFM-IR for characterization of nanosized phages present in extremely low quantity in spray-dried particles. These biologically active phages were shown to retain their physical and chemical integrity in the spray-dried particles.

Pre-gelation assisted spray drying of whey protein isolates (WPI) for microencapsulation and controlled release

Pre-gelation of whey protein isolates (WPI), a milk protein, has been performed before spray drying to decrease the solubility of WPI. The heat-induced pre-gelation at 80 °C aims to produce the gelled WPI for microencapsulation and sustained releases. The gelation time has been studied for a good spray drying, since the feed solutions with higher viscosities cannot be spray dried. WPI solutions cannot be gelled at lower pHs. SEM images show that the spray-dried WPI-acetaminophen particles have wrinkled surfaces. With longer gelation, the spray-dried particles show larger particle sizes and greater changes in the protein structure. FTIR and DSC analysis suggest that the model ingredient (acetaminophen) is amorphous in the spray-dried particles. The release profiles of pre-gelled WPI tablets show good fittings to a first-order release model. Overall, the releases of acetaminophen have occurred over periods from 3 h to two days for different pre-gelation times. The first-order release constants have been determined.

Effect of Spray-Dried Particle Morphology on Mechanical and Flow Properties of Felodipine in PVP VA Amorphous Solid Dispersions

Amorphous solid dispersions (ASDs) are commonly used to enhance the oral absorption of drugs with solubility or dissolution rate limitations. Although the ASD formulation is typically constrained by physical stability and in vivo performance considerations, ASD particles can be engineered using the spray-drying process to influence mechanical and flow properties critical to tableting. Using the ASD formulation of 20% w/w felodipine dispersed in polyvinyl pyrrolidone vinyl acetate, spray-drying atomization and drying conditions were tuned to achieve 4 different powders with varying particle properties. The resulting particles ranged in volume moment mean diameter from 4 to 115 μm, bulk density from 0.05 to 0.38 g cm−3, and morphologies of intact, collapsed, and fractured hollow spheres. Powder flowability by shear cell ranged from poor to easy flowing, whereas mechanical property tests suggested all samples will produce strong tablets at reasonable solid fractions and compression pressures. In addition, Hiestand dynamic tableting indices showed excellent dynamic bonding for 3 powders, and low viscoelasticity with high brittleness for all powders. This work demonstrates the extent spray-dried ASD particle morphologies can be engineered to achieve desired powder flow and mechanical properties to mitigate downstream processing risks and increase process throughput.

Investigation of the molecular state of 4-aminosalicylic acid in matrix formulations for dry powder inhalers using solid-state fluorescence spectroscopy of 4-dimethylaminobenzonitrile

Carrier-free method is an alternative approach for dry powder inhaler (DPI) formulations, which overcome poor drug mobility and distribution. Here we investigated the properties of an active pharmaceutical ingredient (API) within composite particles. We used highly-branched cyclic dextrin (HBCD) as the excipient matrix that was prepared using a spray-drying technique. 4-Aminosalicylic acid (4-ASA) and 4-dimethylaminobenzonitrile (DMABN) were selected as a hydrophilic second-line antitubercular agent and a surrogate for 4-ASA as a model compound, respectively. The spray-dried particles (SDPs) containing 4-ASA or DMABN with HBCD had geometric median diameters (D50) of 2.34 ± 0.07 μm and 2.26 ± 0.10 μm, respectively. Further, the in vitro aerodynamic properties were similar for SDPs containing 4-ASA and DMABN with HBCD. To determine the properties of APIs within composite particles, we performed solid-state fluorescence spectroscopy of DMABN. As a candidate excipient, hydroxypropyl methylcellulose (HPMC) was compared to HBCD. We determined the intensity ratio of twisted intramolecular charge transfer (TICT) emission to locally excited emission within the excipient matrix environment. The HBCD matrix environment was better than HPMC to trigger a more robust TICT reaction of DMABN. A potent state-changing interaction of APIs occurred in the HBCD matrix environment versus another excipient environment.

Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis

Leishmaniasis is a neglected tropical disease affecting more than 12 million people worldwide, which in its visceral clinical form (VL) is characterised by the accumulation of parasites in the liver and spleen, and can lead to death if not treated. Available treatments are not well tolerated due to severe adverse effects, need for parenteral administration and patient hospitalisation, and long duration of expensive treatments. These treatment realities justify the search for new effective drugs, repurposing existing licensed drugs towards safer and non-invasive cost-effective medicines for VL. In this work, we provide proof of concept studies of butenafine and butenafine self-nanoemulsifying drug delivery systems (B-SNEDDS) against Leishmania infantum. Liquid B-SNEDDS were optimised using design of experiments, and then were spray-dried onto porous colloidal silica carriers to produce solid-B-SNEDDS with enhanced flow properties and drug stability. Optimal liquid B-SNEDDS consisted of Butenafine:Capryol 90:Peceol:Labrasol (3:49.5:24.2:23.3 w/w), which were then sprayed-dried with Aerosil 200 with a final 1:2 (Aerosil:liquid B-SNEDDS w/w) ratio. Spray-dried particles exhibited near-maximal drug loading, while maintaining excellent powder flow properties (angle of repose <10°) and sustained release in acidic gastrointestinal media. Solid-B-SNEDDS demonstrated greater selectivity index against promastigotes and L. infantum-infected amastigotes than butenafine alone. Developed oral solid nanomedicines enable the non-invasive and safe administration of butenafine as a cost-effective and readily scalable repurposed medicine for VL.

Fabrication and Characterization of &lt;i&gt;Taraxacum platycarpum&lt;/i&gt; Extract-loaded Particles for Tablet Dosage Form

To develop Taraxacum platycarpum extract (TP)-loaded particles for tablet dosage form, various TP-loaded particles composed of TP, dextrin, microcrystalline cellulose (MCC), silicon dioxide, ethanol, and water are prepared using a spray-drying method and fluid-bed-drying method. Their physical properties are evaluated using angle of repose, Hausner ratio, Carr’s index, hardness, disintegrant time, and scanning electron microscopy. Optimal TP-loaded particles improve flowability and compressibility. Furthermore, 2% silicon dioxide gives increased flowability and compressibility. The formula of TP-loaded fluid-bed-drying particles at a TP/MCC/silicon-dioxide amount of 5/5/0.2 improves the angle of repose, Hausner ratio, Carr’s index, hardness, and disintegrant time as compared with the TP-loaded spray-drying particles. The TP-loaded fluid-bed-drying particles considerably improve flowability and compressibility (35.10° vs. 40.3°, 0.97 vs. 1.17, and 18.97% vs. 28.97% for the angle of repose, Hausner ratio, and Carr’s index, respectively), hardness (11.34 vs. 4.7 KP), and disintegrant time (7.4 vs. 10.4 min) as compared with the TP-loaded spray-drying particles. Thus, the results suggest that these fluid-bed-drying particles with MCC and silicon dioxide can be used as powerful particles to improve the flowability and compressibility of the TP.

Microencapsulation of pepsin in the spray-dried WPI (whey protein isolates) matrices for controlled release

The microencapsulation and controlled release of pepsin have been achieved by spray drying with the original, hydrolysed and gelled whey protein isolates (WPI, HWPI, GWPI). The pepsin is in an amorphous state in the spray-dried particles. The survival rate of pepsin is around 84.3–89.4% during spray drying and decreases with increasing inlet temperature from 110 to 190 °C. The optimal inlet temperature for a high yield and a high survival rate of pepsin is 150 °C. The spray-dried proteins have wrinkled surfaces, which are related to high Peclet numbers during drying. FTIR spectra show free amino acids for HWPI and the change in protein structure for GWPI upon gelation, compared with WPI. The spray-dried samples with microencapsulated pepsin have been tableted for the controlled release studies. The release time is controllable within 4 h by changing the release matrices or the pepsin ratio. Zero-order release of pepsin has been relatively achieved with the highest R-squared value of 0.989 using a sandwich-like multilayer design for a matrix containing 50% GWPI and 50% WPI.

Effect of thermal and shear stresses in the spray drying process on the stability of siRNA dry powders

Pulmonary delivery of small interfering RNAs (siRNAs) has shown promising results for the treatment of lung diseases with gene disorders. The aim of this work was to evaluate the effect of processing-induced thermal and shear stresses during the spray drying process on the solid-state properties, the chemical integrity and the bioactivity of spray-dried siRNA powder intended for inhalation. To this end, inhalable siRNA dry powders composed of EGFP-siRNA and mannitol were prepared by using a lab-scale spray drier. Scanning electron microscopy (SEM), laser diffraction, and X-ray powder diffraction (XRPD) were used to characterize the solid-state properties of the spray-dried siRNA-mannitol powders. High performance liquid chromatography (HPLC) and flow cytometry were exploited to assess the chemical stability and cellular transfection efficiency of siRNA formulations, respectively. The results showed that the spray-dried particles changed from spherical to irregular shape with an increase in the inlet temperature. The high inlet temperature and intensive atomization conditions resulted in more agglomerates in the spray-dried particles. XRPD analysis indicated that the presence of siRNA affected the polymorphic form of mannitol in the spray-dried powder. Compromised chemical stability and cell transfection efficiency of siRNA were observed with an increase in the thermal stress and shear stress during the spray drying process. The chemical stability of siRNA in liquid state was more prone to thermal stress when compared to the stability in the solid-state. In conclusion, stable siRNA based particles for inhalation purposes could be produced using the spray drying technology.

Particle design and oxidation kinetics of iron-manganese oxide redox materials for thermochemical energy storage

High-temperature thermochemical energy storage shows promise in aiding concentrating solar power plants to meet variable, grid-scale electricity demand. In this work, manganese oxide-based mixed metal oxide particles have been designed and tested for thermochemical energy storage. Particles are designed for high energy storage capacity, flowability, and physical and chemical stability. We evaluate the effects of Al2O3, Fe2O3, and ZrO2 in Mn2O3-based spray-dried particles in a TGA between 650 °C and 1200 °C over six consecutive redox cycles. Results are compared with thermodynamic predictions from 400 to 1400 °C under oxidizing and reducing atmospheres. A mixture of 2:1 Fe2O3:Mn2O3 formed iron manganese oxide spinel (MnFe2O4) on calcination, demonstrated the highest thermochemical activity. Intensive mixing was also investigated as a method for preparing MnFe2O4 spinel. Sodium contained in binders/precursors used for spray drying results in the formation of slag phases which negatively impact spray dried particle redox. Spherical particles formed by intensive mixing provided for superior redox reaction. Differential scanning calorimetry (DSC) was performed on MnFe2O4 particles prepared by intensive mixing. The oxidation reaction kinetics of MnFe2O4 was investigated using solid-state kinetics theory and XRD analysis. The reaction proceeds by two different reaction mechanisms. The reaction first proceeds by a diffusion-controlled reaction mechanism (192 ± 2 kJ mol−1 activation energy) with no phase change, followed by a nucleation-growth reaction mechanism (181.4 ± 0.3 kJ mol−1 activation energy). The work reported here supports using low cost MnFe2O4 spinel, formed by intensive mixing of a 2:1 Fe2O3:Mn2O3 composition, as a desirable thermochemical storage active material. Additionally, these results demonstrate the benefit of operating the redox cycle through a cation-vacancy mechanism where the spinel phase maintains its crystal structure and where the reaction rate is stable/robust regardless of particle size.

Lysozyme-Responsive Spray-Dried Chitosan Particles for Early Detection of Wound Infection.

Infections are a severe health issue, and the need for an early point-of-care diagnostic approach for wound infections is continuously growing. Lysozyme has shown a great potential as a biomarker for rapid detection of wound infection. In this study, spray-drying of labeled and derivatized chitosans was investigated for the production of small particles responsive to lysozyme. Therefore, various chitosans, differing in their origin (snow crab, Chionoecetes sp., with medium and low molecular weight or shrimp) were N-acetylated, labeled with reactive black 5, and tested for solubility and spray-drying suitability. Reactive black-5-stained N-acetylated chitosan (low molecular weight, origin crab) was successfully spray-dried, and the obtained particles were characterized regarding size, ζ potential, and morphology. The particles showed an average hydrodynamic radius of 612.5 ± 132.8 nm. ζ potential was measured in the context of a later application as an infection detection system for wound infections in artificial wound fluid (−6.14 ± 0.16 mV) and infected wound fluid (−7.93 ± 1.35 mV). Furthermore, the aggregation behavior and surface structure were analyzed by using scanning electron microscopy and confocal laser scanning microscopy revealing spherical-shaped particles with explicit surface topologies. Spray-dried N-acetylated chitosan particles showed a 5-fold increase in lysozyme-responsive release of dyed chitosan fragments due to the enhanced surface area to volume ratio when compared to non-spray-dried N-acetylated chitosan flakes. On the basis of these results, the study showed the improved properties of N-acetylated spray-dried chitosan particles for future applications for early and rapid infection detection.

Spray-Dried PulmoSphere™ Formulations for Inhalation Comprising Crystalline Drug Particles.

Over the past 20years, solution-based spray dried powders have transformed inhaled product development, enabling aerosol delivery of a wider variety of molecules as dry powders. These include inhaled proteins for systemic action (e.g., Exubera®) and high-dose inhaled antibiotics (e.g., TOBI® Podhaler™). Although engineered particles provide several key advantages over traditional powder processing technologies (e.g., spheronized particles and lactose blends), the physicochemical stability of the amorphous drug present in these formulations brings along its own unique set of constraints. To this end, a number of approaches have been developed to maintain the crystallinity of drugs throughout the spray drying process. One approach is to spray dry suspensions of micronized drug(s) from a liquid feed. In this method, minimization of drug particle dissolution in the liquid feed is critical, as dissolved drug is converted into amorphous domains in the spray-dried drug product. The review explores multiple formulation and engineering strategies for decreasing drug dissolution independent of the physicochemical properties of the drug(s). Strategies to minimize particle dissolution include spray blending of particles of different compositions, formation of respirable agglomerates of micronized drug with small porous carrier particles, and use of common ions. The formulations extend the range of doses that can be delivered with a portable inhaler from about 100ng to 100mg. The spray-dried particles exhibit significant advantages in terms of lung targeting and dose consistency relative to conventional lactose blends, while still maintaining the crystallinity of drug(s) in the formulated drug product.

Smart release-control of microencapsulated ingredients from milk protein tablets using spray drying and heating

There have been many materials used for controlled release of ingredients, but only a few are food-grade for humans. The milk proteins, including casein (relatively insoluble) and WPI (soluble whey protein isolates), have been engineered and used as shell materials in spray-dried particles for controlled release of microencapsulated ingredients (acetaminophen, coffee and ascorbic acid) in this work. Smart and customized control of the release time from a few minutes to a few hours, and then to over two days has been achieved using milk proteins with techniques that include acid-gelation, spray drying and/or heat-gelation. The release rate can be easily controlled by varying the ratio of milk proteins, where the casein-gel tablets require 24 h to be degraded in SGF (simulated gastric fluid) at 37 °C but WPI tablets can be degraded within 1.5 h. The time required for releasing 80% of the ingredients from milk protein tablets follows the order: casein-acetaminophen > casein-coffee > casein-ascorbic acid > casein-WPI-acetaminophen > casein-WPI-coffee > casein-WPI-ascorbic acid > WPI-acetaminophen > WPI-coffee > WPI-ascorbic acid. Characteristics of the spray-dried particles have been studied by FTIR and DSC. After the heat treatment, the milk protein tablets containing acetaminophen (for pain relief) have shown slower release rates. Typically, only 80% acetaminophen has been released within 24 h from the heated casein-acetaminophen tablet, and the release period is over two days.

Particle Surface Roughness Improves Colloidal Stability of Pressurized Pharmaceutical Suspensions.

The effects of particle size and particle surface roughness on the colloidal stability of pressurized pharmaceutical suspensions were investigated using monodisperse spray-dried particles. The colloidal stability of multiple suspensions in the propellant HFA227ea was characterized using a shadowgraphic imaging technique and quantitatively compared using an instability index. Model suspensions of monodisperse spray-dried trehalose particles of narrow distributions (GSD< 1.2) and different sizes (MMAD= 5.98μm, 10.1μm, 15.5μm) were measured first to study the dependence of colloidal stability on particle size. Particles with different surface rugosity were then designed by adding different fractions of trileucine, a shell former, and their suspension stability measured to further study the effects of surface roughness on the colloidal stability of pressurized suspensions. The colloidal stability significantly improved (p< 0.001) from the suspension with 15.5μm-particles to the suspension with 5.98μm-particles as quantified by the decreased instability index from 0.63 ± 0.04 to 0.07 ± 0.01, demonstrating a strongly size-dependent colloidal stability. No significant improvement of suspension stability (p> 0.1) was observed at low trileucine fraction at 0.4 % where particles remained relatively smooth until the surface rugosity of the particles was improved by the higher trileucine fractions at 1.0 % and 5.0 %, which was indicated by the substantially decreased instability index from 0.27 ± 0.02 for the suspensions with trehalose model particles to 0.18 ± 0.01 (p< 0.01) and 0.03 ± 0.01 (p< 0.002) respectively. Surface modification of particles by adding shell formers like trileucine to the feed solutions of spray drying was demonstrated to be a promising method of improving the colloidal stability of pharmaceutical suspensions in pressurized metered dose inhalers.

A Taguchi approach production of spray-dried whey powder enriched with nanoencapsulated vitamin D3

The objective of the present study was to investigate the effect of inlet air temperature of spray drying and different combinations of carrier agents (maltodextrin (MD), gum Arabic (GA), modified starch (MS), and whey protein concentrate (WPC)) on the physicochemical characteristics of spray-dried whey powder, enriched with vitamin D3 to improve its usage as a functional ingredient. Firstly, vitamin D3 was nanoencapsulated by nanoliposome prepared with egg yolk lecithin, sesame oil, and glycerol through thin-film dispersion method. The mean particle size of prepared nanoliposomes was 140 nm. Then, the prepared nanocarriers loaded with vitamin D3 were added into the feed solution and dried through spray dryer. The effect of carrier agent types and inlet air temperature on the physicochemical (moisture content, solubility, porosity, color, and powder yield) and microstructure properties of obtained spray-dried powders were investigated. The optimal carrier agents and condition of spray drying were selected by Taguchi design. Our results showed that the inlet air temperature and carrier agent had significant effects on the characterization of powders. Powders produced by 2% WPC, 3% MS, and 25% MD at 170 °C inlet air temperature showed the highest powder yield (96.4%). Also, the morphology of powders was affected by carrier agent types; increase in MD concentration in feed solution causes to create smoother and spherical spray-dried powder particles.

Trehalose Limits Fragment Antibody Aggregation and Influences Charge Variant Formation in Spray-Dried Formulations at Elevated Temperatures.

The preparation of PLGA rods for sustained release applications via a hot-melt extrusion process employs heat and mechanical shear. Understanding protein stability and degradation mechanisms at high temperature in the solid state is therefore important for the preparation of protein-loaded PLGA rods. The stability of a model protein, labeled Fab2, has been investigated in solid-state formulations containing trehalose at elevated temperatures. Spray-dried formulations containing varying levels of trehalose were exposed to temperatures ranging from 90 to 120 °C. Measurement of aggregation and chemical degradation rates suggests that trehalose limits Fab2 degradation in a concentration-dependent manner, but the effect tends to saturate when the mass ratio of trehalose to protein is around 1 in the solid formulation. The Fab2 secondary structure and spray-dried particle morphology were studied using circular dichroism and scanning electron microscopy techniques, respectively. On the basis of temperature and trehalose-dependent aggregation kinetics as well as changes in spray-dried particle morphology, a mechanism is proposed for the trehalose stabilization of proteins in solid state at elevated temperatures. The results reported here suggest that when fragment antibodies in the solid state are formulated with trehalose as excipient, a high temperature process such as hot-melt extrusion can be successfully accomplished with minimal degradation.

Effect of surfactant level on properties of celecoxib amorphous solid dispersions

The aim of this study was to explore the influence of d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) on the properties of celecoxib (CEL) amorphous solid dispersions (ASDs). ASDs consisting of CEL (20%), copovidone (CoPVP), and TPGS at various levels (0, 5, 10, and 20%) were prepared using spray drying. At 20% level, TPGS increased the dissolution rate and supersaturation of CEL ASDs. These improvements were attributed to three mechanisms: (1) improved powder wetting, (2) enhanced nanoaggregate formation, and (3) improved solubility due to the formation of TPGS micelles. TPGS was also found to affect the particle morphology of spray-dried CEL ASDs. As the TPGS level increased, the shape of the spray-dried particles transitioned from shriveled to spherical. In this ternary system, CEL was found to improve the miscibility between TPGS and CoPVP.

Development of porous particles using dextran as an excipient for enhanced deep lung delivery of rifampicin

This study aimed to develop a dry powder inhaler (DPI) formulation for enhanced deep lung delivery of rifampicin using dextrans of different molecular weights. Porous particles were formed by a spray-drying method, which was designed based on the Peclet number. The morphology of particles containing both rifampicin and dextran was dependent on the dextran concentration. The D50 values of SDPs containing rifampicin and dextran 40 or 70 at ratios of less than 1:10 were below 5 μm. The specific surface area values of spray-dried particles containing rifampicin and dextran 40 or 70 of more than 1:10 were over 20 m2/g, assuming that an increase in specific surface area was indicative of an increase in the formation ratio of a porous structure. DPI formulations that contained higher amounts of dextran had higher rifampicin contents. Thus, the formulations containing a dextran: rifampicin ratio of 1:20 had approximately 100% drug encapsulation.The formation of the porous particles can be explained by the related Peclet number, which correlates with the viscosity and surface tension of the ethanol-water solution used in preparing the particles. It was noted that the existence ratio of the porous particles increased as the viscosity of the mixed solution was increased. Furthermore, an increase in the proportion of dextran resulted in higher rifampicin loading into the particles and the formation of finer particle fractions (FPF) (<7.0 μm at a rate of 28.3 L/min, <4.8 um at a rate of 60.0 L/min). The formulations containing rifampicin and both dextrans at a ratio of more than 1:10 consisted of approximately 50% FPF at a rate of 28.3 L/min and 60.0 L/min. The results indicate that dextran is suitable to obtain porous particles via spray-drying. Additionally, the existence ratio of the porous particles can be improved by increasing the viscosity of the solution used in the preparation of the particles.

Development of porous spray-dried inhalable particles using an organic solvent-free technique

A simple technique to produce spray-dried porous particles for inhalatory administration was developed. The particles were produced using water as solvent, Sodium Cromoglycate as model drug and ammonium bicarbonate as pore forming agent. A central composite design was employed to study the influence of the: pore-forming agent concentration (in the drug aqueous solution fed to the spray dryer) and air inlet temperature on: process yield and powder properties. The powder particle size distribution, moisture content, densities and estimated aerodynamic diameters were studied. Also, particles morphology, hygroscopicity, surface area, in vitro aerosolization properties, dissolution rate and stability were evaluated for some selected samples. In addition, a novel friability test was proposed for mechanical resistance evaluation of the porous materials.A pore forming agent concentration of 1.25% (w/w) and an air inlet temperature of 170 °C were the optimal process parameters to produce porous particles suitable for inhalatory administration. The process yield was high and it was demonstrated that the particles were free of ammonium bicarbonate. The porous powder, obtained by a simple and scalable technique, exhibited low tap density, good stability even at long storage periods (12 months), appropriate mechanical resistance, high initial dissolution rate and excellent aerosolization performance.

Spray dried solid dispersions of piroxicam in carboxymethyl sago cellulose using aqueous solvents: A simple, novel and green approach to produce enteric microparticles with enhanced dissolution

Piroxicam-CMSC solid dispersions were produced by spray drying from aqueous solvents. Depending on the drug-polymer ratio, loading and entrapment efficiency of CMSC microparticles were 6.8–46.75 and 40.79–60.35% w/w, respectively. Scanning electron microscopy revealed non-spherical geometry and agglomeration of the spray-dried particles. The average size of the particles ranged from 7 to 170 µm. Infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction confirmed intact crystalline piroxicam in the microparticles. In gastric pH, microparticles and native piroxicam have shown less than 25% and more than 45% of drug dissolution, respectively in 2 h. In contrast, at pH 7.4, microparticles have shown 80% of drug dissolution; whereas native piroxicam achieved only 30% of dissolution by 30 min. The spray-dried CMSC particles are efficient in restricting drug release in gastric pH and enhance drug dissolution in intestinal pH. The method is eco-friendly as it uses aqueous solvents and non-toxic materials.

Controlled release of caffeine from tablets of spray-dried casein gels

The controlled release of caffeine from the casein gel tablets has been achieved over release periods lasting from a few minutes to over a few days. A novel casein gel has been acidified at pH of 1.0 as the insoluble controlled-release matrix and spray-dried with coffee for microencapsulation. The optimal inlet temperature of spray drying for the casein-coffee mixtures has been found to be 150 °C. The elastic casein-coffee tablets have been engineered without denaturing the components (as indicated by DSC and FTIR analysis). Pressure-controlled release has been achieved for the casein-coffee tablets prepared by compression at 8 (with lactose excipient), 80 and 160 MPa. The corresponding releases of over 80% caffeine are about 24, 12 and 3–6 h, respectively. By changing the coffee/casein ratio from 10 to 100%, the release time of 80% caffeine can be controlled from 24 to 0.5 h. The spray-dried casein-coffee particles shown in the SEM images are similar in size (about 10 μm) and shape (raisin-like). No significant interactions between the casein and coffee components have been observed by FTIR analysis.