Near-critical fluid micronization of stabilized vaccines,antibiotics and anti-virals

Fine powder preparations of vaccines hold promise in resolving many issues encountered in the transport and delivery of vaccines such as loss of potency during transport through the ‘cold chain’ and needle free delivery. We have demonstrated the efficacy of a new powder-generating technique, Carbon dioxide Assisted Nebulization with a Bubble Dryer^® (CAN-BD), for producing dry, active powders of vaccines and small molecule pharmaceuticals. A hepatitis B surface antigen (HBsAg) protein vaccine and a live-attenuated measles vaccine were stabilized in various formulations, then processed into fine powders by nebulizing and drying them at near ambient temperatures (50 °C). Full preservation of HBsAg ELISA activity was achieved for formulations containing sufficient amounts of stabilizing trehalose. The powders were stored for 43 days either at −20 °C or at +66 °C without loss of potency. Commercial live-attenuated virus measles vaccine was further stabilized by adding trehalose or sucrose to retain full potency through CAN-BD drying. Powders had a mass median aerodynamic diameter (MMAD) of 1.9 μm and respirable mass fraction of 94%. A formulation of the anti-viral zanamivir was micronized to give 73% respirable mass fraction and MMAD of 2.4 μm. The antibiotic rifampin was processed by CAN-BD to yield powder with an MMAD of 1.2 μm and 86% respirable mass fraction.     

Microparticulated Hydrochlorothiazide Solid Dispersion: Enhancing Dissolution Properties via Spray Drying

The aim of the present study was to obtain microparticles of hydrochlorothiazide, a diuretic drug that practically insoluble in water, by spray drying and to investigate the influence of process parameters using a three-level, three-factor Box-Behnken design. Process yields, moisture content, particle size, flowability, and solubility were used to evaluate the spray-dried microparticles. The data were analyzed by response surface methodology using analysis of variance. The independent variables studied were outlet temperature, atomization pressure, and drug content. The formulations were prepared using polyvinylpyrrolidone and colloidal silicon dioxide as the hydrophilic carrier and drying aid, respectively. The microparticle yield ranged from 18.15 to 59.02% and resulted in adequate flow (17 to 32°), moisture content between 2.52 to 6.18%, and mean particle size from 45 to 59 µm. The analysis of variance showed that the factors studied influenced the yields, moisture content, angle of repose, and solubility. Thermal analysis and X-ray diffractometry evidenced no drug interactions or chemical modifications. Photomicrographs obtained by scanning electron microscopy showed spherical particles. The solubility and dissolution rates of hydrochlorothiazide were remarkably improved when compared with pure drug. Therefore, the results confirmed the high potential of the spray-drying technique to obtain microparticulate hydrochlorothiazide with enhanced pharmaceutical and dissolution properties.     

The formulation of powder coatings using solid state shear extrusion

The feasibility of producing homogeneous powder coating formulations without melting is investigated using Solid State Shear Extrusion (SSSE). A detailed comparison between conventional melt extrusion and SSSE processing conditions of identical formulations is accomplished by following the behavior and degree of polymerization during curing. Commercially available polyester and epoxide powder coating premix formulations were processed by SSSE using a Brabender® laboratory‐scale twin‐screw extruder and further pulverized in a ball mill. Calculations based on particle size before and after comminution in single batch ball mill studies indicate a reduction in energy requirements for SSSE during pulverization. Metal coupons were coated with dry pulverized formulations using an electrostatic fluidized bed coating system. The dynamics of curing were followed for a series of bake time exposures. The sol was separated from the gel using Soxhlet methods and characterized by gel permeation chromatography (GPC). A comparison of experimentally determined gel points and gelation dynamics showed general agreement between both processing methods. The critical yield stress, determined from preliminary mechanical testing of modified thick adherend specimens crack‐line‐loaded in compression, was also determined. Results showed the SSSE process to be equivalent to melt extrusion.     

COMPARISON OF GLASS TRANSITION TEMPERATURE AND STICKY POINT TEMPERATURE FOR SKIM MILK POWDER

Wall deposition of particles in spray dryers is a key processing problem, and information about the glass transition temperature of the amorphous material that arises from spray drying can be used to guide the selection of operating conditions that may minimise wall deposition. The glass transition temperatures for skim milk powder with various moisture contents were determined using Differential Scanning Calorimetry (DSC), and a repeatable glass transition temperature diagram was established from these results. The glass transition temperature decreased as the moisture content increased, as expected (low moisture content 1.65 g/100 g of dry powder, glass transition temperature 87.7°C; high moisture content 4.52 g/100 g of dry powder, glass transition temperature 46.7°C). The glass transition temperature was found to be virtually the same as the sticky-point temperature measured using a thermo-mechanical test. The difference is essentially due to the difference between doing a mechanical test for viscosity (sticky-point) and a phase transition measurement (DSC).     

Spray-dried Cefixime Encapsulated Poly(lactide-co-glycolide) Microparticles: Characterization and Evaluation of In Vitro Release Kinetics with Antibacterial Activity

Our study reports on the development of novel biodegradable microparticles prepared by a spray-drying technique using the poly(lactide-co-glycolide) (PLGA), a biodegradable polymer for the controlled delivery of cefixime. Cefixime is a water-soluble drug having short biological half-life of 3 h. The behavior of PLGA in controlling drug release responses of cefixime microparticles was investigated. The resultant microparticles were characterized by scanning electron microscopy, encapsulation efficiency, particle-size distribution, X-ray diffraction, and in vitro dissolution studies (pH 7.2). To investigate the type of release mechanism that occurs, dissolution data were plotted according to different kinetic models. The in vitro release profiles from microparticles followed first order and Higuchi model release. Antibacterial studies were carried out using a standard agar diffusion method to determine the effectiveness of formulations in inhibiting the growth of microorganisms. It showed that the released drug from the formulations was effectively inhibiting the growth of microorganisms with the minimum inhibitory concentration of < 1 µg/mL. Data revealed the potential of formulations for treatment of infections caused by various microorganisms. Thus, this study demonstrates the high potential of the spray-drying technique to obtain stable cefixime microparticles with good encapsulation efficiency to achieve a delivery profile that would yield the controlled released level of the drug over a long period of time (74 h).     

Sweet Potato Starch Microparticles as Controlled Drug Release Carriers: Preparation and In Vitro Drug Release

The aim of this study was to investigate the in vitro drug release behavior of sweet potato starch (SPS) microparticles intended for controlled drug delivery applications. Diclofenac sodium (DS) was used as a model drug candidate in the present study. SPS microparticles were prepared using a spray-drying technique by varying the polymer concentration and drug loading. The mean particles size of drug-loaded spray-dried SPS microparticles was between 10.3 and 13.1 µm. The mean particle size increased slightly with increase in the concentration of SPS. The mean particle size of spray-dried SPS microparticles increased from 10.3 to 13.1 µm when the concentration of SPS increased from 2 to 4% w/v. Under the current spray-drying conditions, the percentage yield of spray-dried SPS microparticles did not vary much among the various formulations and it was between 65.2 and 70.1%. The encapsulation efficiencies of SPS microparticles formulations was between 95.1–98.2%, suggesting good encapsulating ability of the SPS polymer by spary drying. Drug release from all the formulations of spray-dried SPS microparticles was controlled over period of 6 h. The cumulative amount of drug release from the spray-dried SPS microparticles decreased with an increase in the concentration of SPS, while it increases as the drug loading is increased. Release of the drug from spray-dried SPS microparticles followed Fick's law of diffusion since a good correlation coefficient (R²) was observed with the Higuchi plots (R² = 0.9928 to 0.9979).     

Orange juice residues as dietary fiber source for foods

Food snacks using powdered residues from the orange juice industry as a source of dietary fiber were formulated. Six formulations utilizing powdered orange residues with three different moisture levels (25%, 15% and 10%) were elaborated. There were used two basic blends. The first one was 33.3% of orange dry powder, 33.3% of honey, 16.6% of roasted peanut, 16.6% of raisins; the second one was 28.6% of orange powder, 35.7% of honey, 17.85% of roasted peanut, 17.85% of raisins. Snacks had spherical shape with 2.5 cm diameter and a weight close to 10g. The snack moisture was between 12.6 and 17.4%, and their aw between 0.65 and 0.71. The snack chemical composition, on dry matter basis, was 1.6 and 1.9% of ash; 12.3 and 15.2% of lipids; 6.1 and 7.1% of proteins; and 56.2 to 59.6% of carbohydrates; the caloric contribution (calculated) was between 326.8 and 342.9 kcal/100g. The powdered orange residue had 64% of total dietary fiber, 54% of insoluble dietary fiber and 10% of soluble dietary fiber. In the snack the fiber amount fluctuated between 20 and 26% of total dietary fiber; 18 and 22% of insoluble dietary fiber, and 3.0 and 4.5% of soluble dietary fiber. The snack with the higher content of orange residue presented the higher content of dietary fiber. The snacks were well accepted by a sensory panel, without showing differences among treatments.     

Characterization of fractionated phenolic resins used in photoresists

Novolak resins fractionated using a liquid/liquid centrifugal fractionation/separation technique were characterized and contrasted to resins fractionated by conventional methods. The new fractionation method resulted in higher yields of resins with comparable or improved functional properties when used in i‐line sensitive (365 nm) photoresist formulations. By characterizing the isolateld resin and the lower molecular weight (Mw) fractions removed during fractionation, a better understanding of the structural differences associated with the fractionation processes could be determined. The potential for improving the fractionation/separation process and for obtaining higher yields and more consistent resists with the resins was identified.     

Phage as a diagnostic – the use of phage in TB diagnosis

Rapid TB diagnosis and drug susceptibility testing is limited by the slow growth of the causative organism, Mycobacterium tuberculosis (MTB). Effective and rapid methods for the detection and drug susceptibility testing of TB, that are suitable for implementation in low income countries, which bear the highest TB burden, are urgently needed for effective identification, treatment and control of the disease. Mycobacteriophages have the potential to become useful tools in the diagnosis of TB, as they are specific for mycobacteria and only replicate in, and hence detect, viable cells. Phage‐based techniques involve simple manual manipulations that typically require little capital expense and yield results rapidly. Two techniques have been developed recently which use mycobacteriophage for the antibiotic susceptibility testing and direct diagnosis of TB from sputum. Luciferase Reporter Phages (LRP) are recombinant phages that contain the gene for the fire‐fly luciferase enzyme. Upon infection of mycobacteria by these phages, this enzyme is produced within a cell. In the presence of this enzyme, light is produced by viable cells that also contain the substrates for the enzyme: ATP and luciferin (added exogenously). The ‘Bronx Box’ has been developed as a low cost means of detecting light signal from mycobacteria infected with LRP using photographic film. A MTB strain's susceptibility to an antibiotic can be assessed by comparing light production, as an indication of the presence of viable cells, in samples pre‐incubated in the presence and absence of the test antibiotic. Susceptibility testing of some of the front line drugs for TB chemotherapy has given excellent results (detection of all resistant isolates), using LRP and the Bronx Box. Phage amplification uses the production of progeny phage, instead of a reporter gene product, to reflect the presence of target bacteria. The technique has been successfully applied to drug susceptibility testing and for diagnosis to the TB from sputum specimens. Viable MTB cells within a specimen are uniquely infected by a bacteriophage reagent. A potent selective virucide destroys all the phage particles that remain outside the cells while remaining inactive against the MTB bacilli (and the phages that have infected them). After the virucide has been neutralised, and phages that are released from infected cells are indicative of TB cells being present in the original specimen. These phages can be easily detected by propagation on lawns of non‐pathogenic rapidly growing mycobacteria. A commercially available test, termed FASTPlaqueTB‐RIF, determines the rifampicin susceptibility of isolates by comparing the viability of cells pre‐treated with and without rifampicin. Results give excellent agreement (97–98% overall) with conventional ‘gold standard’ methods, but in 2 days rather than 3 weeks. Preliminary work has shown that it should be possible to reduce the assay time to 24 h. A variation to this method, FASTPlaqueTB, detects TB directly from sputum specimens and is capable of rapidly reporting the presence of viable MTB cells within 48 h. This technique has achieved excellent specificity (close to 100%) when evaluated in the clinical setting. © 2001 Society of Chemical Industry     

Quality evaluation of Panax notoginseng extract dried by different drying methods

Quality control still remains a big issue, affecting herbs, formulations, and even the practice of Traditional Chinese Medicine. A promising solution to the problem is to take advantage of innovative process techniques including alternative drying methods within the pharmaceutical processing. Nowadays, vacuum belt drying (VBD) has gained more and more importance in food and pharmaceutical processing. In this work, Panax notoginseng extract was made into powder by the gentle VBD as well as by classical spray drying (SD), freeze drying (FD), and vacuum drying (VD). Certain chemical and physical properties of the dried powders such as moisture content, drying time, porosity, density, saponins content, pH value and hydroxyl radicals scavenging activity were evaluated. The results showed the qualities of dried products were influenced to different extent by drying methods certainly. Vacuum belt drying was suggested to dry P. notoginseng extract for its high quality assurance of hygroscopic products and suitable for sticky or high viscous products.     

Spray Congealing of Pharmaceuticals: Study on Production of Solid Dispersions Using Box-Behnken Design

This work aimed at evaluating the spray congealing method for the production of microparticles of carbamazepine combined with a polyoxylglyceride carrier. In addition, the influence of the spray congealing conditions on the improvement of drug solubility was investigated using a three-factor, three-level Box-Behnken design. The factors studied were the cooling air flow rate, atomizing pressure, and molten dispersion feed rate. Dependent variables were the yield, solubility, encapsulation efficiency, particle size, water activity, and flow properties. Statistical analysis showed that only the yield was affected by the factors studied. The characteristics of the microparticles were evaluated using X-ray powder diffraction, scanning electron microscopy, differential scanning calorimetry, and hot-stage microscopy. The results showed a spherical morphology and changes in the crystalline state of the drug. The microparticles were obtained with good yields and encapsulation efficiencies, which ranged from 50 to 80% and 99.5 to 112%, respectively. The average size of the microparticles ranged from 17.7 to 39.4 µm, the water activities were always below 0.5, and flowability was good to moderate. Both the solubility and dissolution rate of carbamazepine from the spray congealed microparticles were remarkably improved. The carbamazepine solubility showed a threefold increase and dissolution profile showed a twofold increase after 60 min compared to the raw drug. The Box-Behnken fractional factorial design proved to be a powerful tool to identify the best conditions for the manufacture of solid dispersion microparticles by spray congealing.     

Zeolite nanocrystals prepared from zeolite microparticles by a centrifugation-assisted grinding method

Different sizes of zeolite nanocrystals were fabricated from zeolite microparticles using a centrifugation-assisted grinding method. The zeolite nanocrystal formation can be attributed to the Al₂O₃ bowl mill generation of mechanical stress that fractured zeolite microparticles into smaller fragments. In the present study, the smaller fragments had a wide distribution of size and morphology. Therefore, different sizes of zeolite nanocrystals could be recovered from these smaller fragments by varying the centrifugation process. Zeolite nanocrystal product yields were measured by periodically recovering the nanocrystals from the smaller fragments based on milled zeolite powder. The larger crystals of zeolite were typically irregular in shape, whereas the smaller zeolite nanocrystals tended to be spherical. High product yield of the zeolite nanocrystals was obtained by periodically removing nanocrystals from the milled zeolite powder and recycling the large zeolite particles. Thus, the results from this new hybrid process suggest that it can be used to fabricate differing sizes of zeolite nanocrystals. In addition, the size of the recovered zeolite nanocrystal products was narrow, and the initial zeolite nanocrystal structure was not destroyed by the mechanical stress.     

A Comparison of Compacting and Caking Behavior of Carbonate-Based Washing Powders

Two types of sodium carbonate powder produced by spray drying (SD) and dry neutralization (DN) were studied for their compaction properties using a uniaxial compression tester. A comparison was also made with Persil washing powder. Dry neutralized sodium carbonate showed greater resistance to compression and also produced a weaker compact when compressed to 100 kPa. Spray-dried sodium carbonate had an absence of fine particles but compacted easily. Differential scanning calorimetry (DSC) showed that both types of powder were predominantly amorphous in nature. Moisture sorption measurements showed that both powders behaved in a similar way below 50% relative humidity (RH). However, dry neutralized sodium carbonate had a high moisture affinity above this RH. Particle structures were also examined using scanning electron microscopy, showing the heterogeneous interior of the spray-dried particles.     

Volatile Retention and Antifungal Properties of Spray-Dried Microparticles of Lippia sidoides Essential Oil

Spray drying microencapsulation of Lippia sidoides essential oil was investigated. Maltodextrin DE10 and gum arabic at different proportions (4:1, 3:2, 2:3, 0:1 m/m) was used as a carrier. The content of essential oil related to the carrier was 20 and 25% in weight and the emulsions were atomized from 30% up to 60% (m/m) of total solid concentration. Spray dryer inlet temperatures varied from 140 to 160°C and the best thermal efficiency and powder recovery were found at 160°C. Product properties and process performance were assessed on the basis of microscopic features of the powder (shape and size of microparticles), moisture content, and powder recovery. Encapsulation efficiency was estimated through determination of the content of essential oil in the microcapsules. The best encapsulation efficiency was related to experimental parameters as follows: solid content of the encapsulating composition of 50% (m/m), maltodextrin:gum arabic ratio of 0:1 (m/m) and carrier:essential oil ratio of 4:1 (m/m). Antifungal activities of microparticles were evaluated, evidencing their potential as important antifungal agents. The positive findings in this study encourage further research and provide perspectives for the development of phytotherapeutic products from essential oil of Lippia sidoides.     

Changes in P Bioavailability Induced by the Application of Liquid and Powder Sources of P, N and Zn Fertilizers in Alkaline Soils

Alkaline and/or calcareous soils provide significant challenges for management of crop P nutrition, due to rapid fixation of P into sparingly soluble forms not readily accessible by plants. Three powder products, mono- and diammonium phosphate (MAP, DAP) and triple superphosphate (TSP), were compared to three liquid products, liquid MAP, ammonium polyphosphate (APP) and phosphoric acid (H₃PO₄), as sources of P for wheat grown in four alkaline soils (grey and red calcareous soils, a Vertosol and a Sodosol) sampled in Eyre Peninsula (South Australia), Wimmera and Central Mallee areas (Victoria) of southern Australia. Soils were labelled with ³²P and the labile P pool and P derived from the fertilizer (P_dff) determined. Residual value of the fertilizers was determined after a 4 month wet/dry incubation. Liquid formulations outperformed powder products in the grey calcareous soil and in the Vertosol, as measured by wheat growth, P uptake, plant-labile P pools and P_dff. These increases in P efficiency were not related to differential acidification of the bulk soils. In the most calcareous soil, large proportions of the added DAP, MAP or TSP were rapidly converted (fixed) into non plant-labile pools, likely through precipitation of Ca–P compounds not accessible to plant roots, while conversely, liquid formulations minimized P fixation. Our results suggest that one of the most likely hypotheses to explain difference in efficiencies between powder and liquid forms of fertilizers was that in relatively dry conditions and in high P fixing soils, the dissolution and diffusion of P outwards from the powder is limited. This induces localized areas in the soil with high concentrations of P leading to precipitation of insoluble Ca–P solid phases. In the field, where powder fertilizers are applied as granules rather than as fine powder, differences between the two forms of fertilizer are likely to be larger. The residual value of liquid formulations was equal or superior to powder products. Liquid fertilizers injected into soil may therefore have potential to improve P nutrition in a wide range of calcareous soils under dryland agriculture throughout the world. Field trials have actually been performed in southern Australia to confirm this important issue.     

Spray-Dried Buccal Mucoadhesive Microparticles of Venlafaxine Based on Cress Seed Mucilage: In Vitro,in Vivo Evaluation in Rabbits

Lepidium sativum Linn. (Cruciferea) is known as garden cress or cress. Venlafaxine is prescribed in schizophrenia and anxiety. It shows a tendency of hepatic first-pass metabolism, which affects its bioavailability. The objective of this study is the extraction of cress seed mucilage and development of buccal mucoadhesive microparticles of venlafaxine based on the mucilage using a spray-drying technique. The optimized formulation was evaluated in vitro and the bioavailability of the same formulation in rabbits was assessed. Cress seed mucilage was extracted and used to prepare microparticles with varying concentrations in formulations F1–F5 (1–5% w/w) using a spray-drying technique. The microparticles were evaluated for yield, particle size, incorporation efficiency, swelling property, in vitro mucoadhesion, and in vitro drug release. Microparticles were characterized by differential scanning colorimetry, scanning electron microscopy, and X-ray diffraction studies. In vivo evaluation was carried out in rabbits. Formulation F5 showed maximum mucoadhesion (88.38 ± 1.46%), greater incorporation efficiency (89.42 ± 2.52%), and the highest swelling index (0.93 ± 0.01) compared to the other formulations. F5 showed a marked increase in bioavailability after buccal administration (52.55%) compared to an oral route (39.40%). Time to reach C _max of 23.49 ± 0.33 ng/mL was 120 min for buccal microparticles in comparison to oral solution, which took 180 min to reach C _max of 17.98 ± 1.14 ng/mL. Cress seed mucilage is suitable for production of the mucoadhesive microparticles using a spray-drying method because significant improvement in bioavailability by buccal mucoadhesive microparticles was observed.     

Spray Drying of Extracts from Red Yeast Fermentation Broth

Red yeast rice is a pigmented material that is traditionally used in Asia as a food colorant. In addition to food applications, red yeast rice is known in traditional Chinese medicine for its therapeutic actions. The aim of this work was to study the quality interactions during spray drying of extracts from the Monascus ruber van Tiegham fermentation broth. The quality indicators used for the dry powder properties were the levels of monacolin K, ratio of red to yellow pigments, as well as their antioxidant activity. The experiments followed a Box-Behnken design to study the effects of the adjuvant/drug ratio, adjuvant incorporation time, and oulet drying temperature on the pharmacotechnical, chemical, and biological properties of the dry extract. The influences of these factors on the characteristics of the dry powder were evaluated by the bulk density, tapped density, Carr index, Hausner factor, residual moisture content, water activity, antioxidant activity, monacolin K, yellow-to-red pigment ratio, and antioxidant activity. The analysis of variance (ANOVA) on experimental data revealed that an increase in drying temperature significantly increased the dry powder yield and caused an improvement in powder flow properties, which may be related to lower moisture contents. The drying temperature did not affect the monacolin K content in dry powder but showed a complex influence on its antioxidant activity. The increase in drying adjuvant-to-drug ratio affected the yield and also indicated a protective effect on the monacolin K content. The duration of drying adjuvant incorporation had little or negligible effect on powder properties. The dry extracts of red yeast rice showed adequate properties and the process proposed herein can be used to prepare nutraceutical products.     

Fabrication of composite microparticles of artemisinin for dissolution enhancement

The main aim of this study is to enhance the dissolution of a poorly water soluble antimalarial drug, artemisinin (ART) by fabricating its microparticles and composites with selected hydrophilic polymers using a spray drier with a modified multi-fluid nozzle. We investigated the spray drying of ART with polyvinylpyrrolidone (PVP) considering the effect of feed ratio (ART:PVP) on the physical properties and dissolution of spray dried ART. Other hydrophilic carriers such as polyethylene glycol (PEG) were selected for comparing the dissolution with that of spray dried ART with PVP. The drug and polymer solutions were supplied through different liquid passages of the modified four-fluid nozzle to fabricate ART and composite microparticles. Characterization of the original ART powder, spray dried ART microparticles and ART-polymer composite microparticles was carried out by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and dissolution tester. The DSC and XRD studies suggested that the crystallinity of ART decreased after spray drying and depended on the weight ratio of drug to polymer. Percent dissolution efficiency (%DE); relative dissolution (RD); mean dissolution time (MDT); difference factor (f₁) and similarity factor (f₂) were calculated for the statistical analysis. The dissolution of ART from the spray dried ART-PVP composite microparticles was more rapid than that from their respective physical mixture, spray dried ART-PEG composite microparticles and original ART powder. In the mathematical modeling, the Weibull and Korsmeyer-Peppas model were found to best fit to the in vitro dissolution data and the drug release kinetics could be recognized as Fickian diffusion. This study demonstrated that the modified multi-fluid spray drier can be used for the preparation of drug microparticles to improve the dissolution ability of poorly water soluble drugs and overcome the problem of finding a common solvent for drugs and carriers.     

Weather-stable low-gloss powder coatings

Manufacturing weather-stable powder coatings with a matte surface and consistent quality is a challenge to the powder coatings industry. Technically acceptable results are achieved using the dry blend process, but one-shot formulations based on polyurethane raw materials or the use of a bifunctional polyurethane matte hardener offer interesting alternative solutions. Investigation of the powder coating films using a perthometer and an electron microscope provides a deeper understanding of the matte powder coating systems. LS-M/IC Geb. Q 24, D-51368 Leverkusen, Germany, e-mails: Peter.Thometzek.PT1@Bayer-AG.de; Ulrich.Freudenberg.UF@Bayer-AG.de; Hans-Ulrich.Meier-Westhues.HM@Bayer-AG.de. Industrial Chemicals Division, Coatings, 100 Bayer Rd., Pittsburgh, PA 15205-9741.     

Direct evidence on reduced adhesion of Salbutamol sulphate particles due to L-leucine coating

Attractive van der Waals forces are responsible for unwanted agglomeration of fine dry powder particles which can cause problems e.g. with inhalable drugs in the treatment of asthma. In this article we report on experimental evidence of reduced adhesion of salbutamol sulphate particles when they are coated with L-leucine. Particle production and coating was performed using an aerosol flow reactor. The L-leucine-containing particles were fully covered with L-leucine as evidenced by X-Ray Photoelectron Spectroscopy and Scanning Electron Microscopy findings. With a suitable concentration of precursor solution the particles become rough and adhesion diminished to one fifth of the adhesion of uncoated particles. The main reason for this reduced adhesion was an increase in surface roughness, which reduced the contact area and the number of contact points thus increasing the effective separation between particles.