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At least 757 records · Page 42Linked to original sources
PubMed2006

Effervescent dry powder for respiratory drug delivery.

The objective of this work was to develop a new type of respiratory drug delivery carrier particle that incorporates an active release mechanism. Spray drying was used to manufacture inhalable powders containing polybutylcyanoacrylate nanoparticles and ciprofloxacin as model substances for pulmonary delivery. The carrier particles incorporated effervescent technology, thereby adding an active release mechanism to their pulmonary route of administration. Effervescent activity of the carrier particles was observed when the carrier particles were exposed to humidity. Gas bubbles caused by the effervescent reaction were visualized by confocal laser scanning microscopy. The images showed that nanoparticles were distributed throughout the gas bubble. For the effervescent formulation the average mass median aerodynamic diameter (MMAD) was 2.17 microm+/-0.42, fine particle fraction (FPF(<=5.6 microm)) was 46.47%+/-15 and the GSD was 2.00+/-0.06. The results also showed that the effervescent carrier particles released 56+/-8% ciprofloxacin into solution compared with 32+/-3% when lactose carrier particles were used. The mean nanoparticle size did not significantly change upon release when the nanoparticles were incorporated into an effervescent formulation. However, the mean size significantly increased upon release when only lactose was used as carrier particle matrix. In conclusion, effervescent carrier particles can be synthesized with an adequate particle size for deep lung deposition. This opens the door for future research to explore this technology for delivery of a large range of substances to the lungs with possible improved release compared to conventional carrier particles.

Administration, Inhalation↗
PubMed1984

[Use of polyacrylate dispersions for spray coating phenobarbital. 1: Production and in vitro study of microcapsules].

The production of microcapsules (model drug: phenobarbital) using aqueous polyacrylate dispersions by means of spray drying is described. The influence of the following factors on formation and quality of the microcapsules is discussed: particle size of the drug, composition of the polyacrylate, viscosity of the spray material and quantitative relation between the drug and the coating material. The morphology of the microcapsules is investigated by means of light and screen electronic microscopy. The liberation of the drug is evaluated. Mainly dry spheric microcapsules arise in a one-working step. Their properties are influenced by variation of the polyacrylate composition. The liberation of the drug decreases with decreasing drug concentration (80-20%) and in dependence of the polyacrylate dispersion for spray coating and the resulting film.

Acrylic Resins↗
PubMed2003

Improvement of insulin absorption from intratracheally administrated dry powder prepared by supercritical carbon dioxide process.

The purpose of this study was to improve insulin absorption from dry powder after administration in lung without an absorption enhancer. The dry powders, with mannitol as a carrier, were prepared with or without an absorption enhancer (citric acid) by supercritical carbon dioxide (SCF) and spray drying (SD) processes. Insulin powder was precipitated from dimethyl sulfoxide and aqueous solutions by dispersing the insulin solutions from parallel and V-type nozzles, respectively, into supercritical carbon dioxide, which is an antisolvent for insulin. In vitro aerosol performance was evaluated with a cascade impactor. Insulin powder containing citric acid prepared by the SCF method (MIC SCF) showed improved inhalation performance compared with insulin powder prepared by the SD process, although the particle size of the former powder was larger than that in powders prepared by SD. Insulin absorption was estimated from the change in plasma glucose level. The blood glucose level after administration of the insulin powder without citric acid prepared by the SCF process (MI SCF) decreased rapidly, and a significant difference was observed for areas under the curve of change in plasma glucose concentration versus time (AUCs) between MI SCF and the insulin powder without citric acid prepared by the SD process (MI SD). These results suggest that the SCF technique would be useful to prepare dry powders suitable for inhalation.

Absorption↗
PubMed2003

Systemic delivery of parathyroid hormone (1-34) using inhalation dry powders in rats.

The aim of this work was to prepare and characterize inhalation dry powders of human parathyroid hormone (PTH), as well as to assess their efficacy for systemic delivery of the peptide and safety in rats. The powders were prepared by spray-drying using PTH, sugars, dipalmitoylphosphatidylcholine, and/or albumin. They presented an average primary particle diameter of 4.5 microm and tap density of 0.06 g/cm(3), a mass median aerodynamic diameter between 3.9 and 5.9 microm, and reached up to 98% emitted dose and up to 61% fine particle fraction in the multi-stage liquid impinger using a Spinhaler inhaler device. Varying the airflow rate from 30 to 100 L/min had limited influence on the aerodynamic behavior of the aerosols. The absolute PTH bioavailability was 21% after intratracheal administration of the powder formed of PTH/albumin/lactose/dipalmitoylphosphatidylcholine and 18% after subcutaneous injection in rats. Equilibrium dialysis revealed a 78% binding of PTH to albumin and the withdrawal of albumin from the powder increased absolute bioavailability after inhalation from 21 to 34%. No acute inflammation appeared in the lung up to 48 h after a single inhalation. The increased bioavailability of the optimized powder aerosol of PTH makes it a promising alternative to subcutaneous injection.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1998

Protein deposition from dry powder inhalers: fine particle multiplets as performance modifiers.

PURPOSE: To evaluate the use of carrier-based dry powder aerosols for inhalation delivery of proteins and examine the effect of fine particle excipients as potential formulation performance modifiers. METHODS: Bovine serum albumin (BSA) was co-processed with maltodextrin by spray-drying to produce model protein particles. Aerosol formulations were prepared by tumble mixing protein powders with alpha-lactose monohydrate (63-90 microns) or modified lactoses containing between 2.5 and 10% w/w fine particle lactose (FPL) or micronised polyethylene glycol 6000. Powder blends were characterised in terms of particle size distribution, morphology and powder flow. Formulation performance in Diskhaler and Rotahaler devices was investigated using a twin stage impinger operating at 60.s51 min-1. RESULTS: Inhalation performance of binary ordered mixes prepared using BSA-maltodextrin and lactose (63-90 microns) was improved by addition of FPL and micronised PEG 6000. For the addition of 5% w/w FPL the protein fine particle fraction (0.5-6.4 microns) using the Diskhaler was increased from 31.7 +/- 2.4% to 47.4 +/- 2.2%. Inclusion of FPL and micronised PEG 6000 changed the bulk properties of inhalation powders and reduced powder flow but did not affect device emptying. Unexpectedly, improvements in performance were found to be independent of the order of addition of FPL to the ternary powder formulations. SEM studies revealed that this was probably the result of a redistribution of protein particles between the coarse carrier lactose component and added FPL during mixing. CONCLUSIONS: Fine particle excipients can be used to improve the performance of carrier-based protein dry powder aerosols. Mechanistically, enhancement of performance is proposed to result from a redistribution of protein particles from coarse carrier particles to the fine particle component in the ternary mix.

Aerosols↗
PubMed2001

Solution-based particle formation of pharmaceutical powders by supercritical or compressed fluid CO2 and cryogenic spray-freezing technologies.

Micronization is an important procedure used in the pharmaceutical industry to reduce the particle size of active pharmaceutical ingredients (APIs). The spray-drying and milling techniques presently used to micronize drug substances cannot be used to process thermolabile or physically unstable drug substances. Therefore, new micronization techniques, including particle precipitation with supercritical or compressed fluid CO2 and spray-freezing of drug solutions and suspensions into cryogenic gas to produce solid frozen microparticles, are currently being perfected for future use in the pharmaceutical industry. This review highlights the compressed gas and cryogenic liquid technologies being developed as potential solution-based particle formation technologies for drugs that cannot be processed by conventional micronization techniques.

Carbon Dioxide↗
PubMed2004

Effect of particle morphology on the triboelectrification in dry powder inhalers.

Electrostatic charge of lactoses of different particle morphology and amorphous contents were measured during actuation from two different dry powder inhalers (DPIs). Triboelectric studies may give important information when new inhaler devices, materials and formulations are designed in order to improve the drug deposition. Two inhalers, Taifun (Focus Inhalation Oy, Finland) and Clickhaler (Innovata Biomed Ltd., UK) were filled with lactose powders which were spray dried from different solutions or suspensions of lactose, ethanol and water. Differences in the amorphous contents were determined with isothermal microcalorimetry (IMC) and X-ray diffraction (XRD) and the particle morphology was examined with laser diffraction and electron microscopy (SEM). Samples were actuated from the inhalers at given intervals into the Faraday pail and the generated charges were recorded. Increase in the water concentration of the feed suspension had negligible effect on the charging until it exceeded 70%. Reproducibility of the measurement was found to be better with samples of homogenous particles and higher crystallinity while more amorphous samples with different morphology and wide particle size distribution showed change in the sign of the charge in addition to higher variations of the magnitude. In this study we show that different inhalers, as well as the morphology of the lactose powder, has noticeable effects on the generated charge which has previously been shown to affect the deposition of the drug and the function of an inhaler.

Crystallization↗
PubMed2006

Lung deposition of mannitol powder aerosol in healthy subjects.

Mannitol as a dry powder aerosol is used for bronchoprovocation testing and to enhance mucus clearance in people with excessive airway secretions. The dose and distribution of the deposited aerosol in the lung was investigated using fast single photon emission tomography (SPECT) imaging. Mannitol powder (3 microm particle size) was produced by spray drying and radiolabeled with (99m)Tc-DTPA. Approximately 60 mg of radiolabeled mannitol (containing 52-68 MBq of (99m)Tc-DTPA) was administered to 10 healthy subjects using the Inhalator dry powder inhaler (DPI), and SPECT images (1 min each) were collected. Thirteen percent to 31% of the dose of mannitol loaded in the inhaler deposited in the lungs and the deposited dose correlated positively with the peak inhalation air flow. The regional aerosol lung distribution, as expressed by the penetration index (i.e., ratio of peripheral to central deposition in the lung) varied from 0.31 to 0.88, which however showed no dependency on any flow parameters. The variation in response to the same dose of mannitol within the asthmatic population may in part be explained by these findings.

Adult↗
PubMed2006

Correlation between inertial impaction and laser diffraction sizing data for aerosolized carrier-based dry powder formulations.

PURPOSE: The purpose of the study was to determine whether the drug fine particle fraction (FPF) from different dry powder aerosol formulations measured by laser diffraction at a range of flow rates correlated with that measured by inertial impaction. MATERIALS AND METHODS: Ten binary formulations were prepared containing 1.5% w/w salbutamol base or sulphate, blended with the sieved (63-90 microm) fraction of different sugars (regular lactose, spray-dried lactose, sorbitol, dextrose or maltose). A further six ternary formulations were prepared containing 1.5% w/w salbutamol sulphate, 97% coarse lactose (63-90 microm) and 1.5% micronised or intermediate-sized lactose (1-50 microm). The FPF particles (< 5 microm) of these formulations were measured by laser diffraction and inertial impaction at flow rates between 28.3 and 100 l min(-1). RESULTS: When only the particles with diameter < 60 microm obtained by laser diffraction were considered the FPF (< 5 microm) could be determined and this enabled the aerosolisation of all 16 blends to be feasibly compared at flow rates ranging from 28.3 to 100 l min(-1). A significant linear correlation was found between the fine fractions measured by laser diffraction and the salbutamol fine fractions determined by inertial impaction (r2 = 0.934). Such correlation was also confirmed for formulations containing added fine lactose. CONCLUSION: Particle size measured by laser diffraction under the employed conditions reflected the aerodynamic properties of the drug. Laser diffraction can be used as on-, in- and/or at-line measurements and controls for dry powder aerosol formulations.

Adrenergic beta-Agonists↗
PubMed2005

Validation of fluid bed granulation utilizing artificial neural network.

Three innovative components (an annular gap spray system, a booster bottom and an outlet filter) have been developed by Innojet Technologies to improve fluid bed technology and to reduce the common interference factors (clogging of nozzles and outlet filters, spray loss, spray drying and fluidized bed heterogeneity). In a fluid bed granulator, three conventional components have been replaced with these innovative components. Validation of the modified fluid bed granulator has been conducted using a generalized regression neural network (GRNN). Under different operating conditions (by variation of inlet air temperature, liquid-binder spray rate, atomizing air pressure, air velocity, amount and concentration of binder solution and batch size), sucrose was granulated and the properties of size, size distribution, flow rate, repose angle and bulk and tapped volumes of granules were measured. To confirm the method's validity, the trained network has been used to predict new granulation parameters as well as granule properties. These forecasts were then compared with the corresponding experimental results. Good correlation has been obtained between the predicted and the experimental data. From these findings, we conclude that the GRNN may serve as a reliable method to validate the modified fluid bed apparatus.

Chemistry, Pharmaceutical↗
PubMed1981

[On the production and the characterization of spray embeddings (author's transl)].

Spray drying of phenobarbital-polyvinyl pyrrolidone (PVP), phenobarbital-polyvinyl alcohol (PVA) and digoxin-PVP solutions yielded embeddings in the form of very fine powders. Depending on the drug-adjuvant ratio, the form in which the drug was embedded in the indifferent carriers was microcrystalline to radio-amorphous. In vitro studies showed that the dissolution of all the spray products was more rapid than that of the corresponding physical mixtures, and that the resulting solutions of the respective drugs were always oversaturated. The oversaturated solutions obtained from embeddings containing the amorphous forms of the difficulty soluble drugs were relatively stable. PVP inhibited the crystallization of phenobarbital to a greater extent than PVA, and led to a higher oversaturation of the drug in the resulting solutions. The in vitro release of digoxin was significantly more rapid from PVP embeddings (and tablets made from them) than from products containing digoxin in crystalline form.

Chemistry, Pharmaceutical↗
PubMed2002

Novel method for detecting bovine immunoglobulin G in dried porcine plasma as an indicator of bovine plasma contamination.

Current U.S. Food and Drug Administration regulations prohibit feeding of protein derived from mammalian tissue, excluding blood and blood products and any product that consists entirely of porcine or equine protein. A novel lateral flow immunoassay device has been developed that can quickly and qualitatively determine the presence of bovine immunoglobulin G (IgG), a major component in blood products, at very low levels (0.01% v/v). The device can be used to test for bovine IgG commingling in spray-dried porcine plasma used in the feed industry. Producers and consumers alike could use this device to verify product content at threshold levels.

Adsorption↗
PubMed2001

Relationships between different hydration properties of commercial and laboratory soybean isolates.

Functional properties related to water protein interactions of soy protein isolates depend on the structural and aggregation characteristics of their major components (storage globulins 7S and 11S) that could be modified by the preparation procedure, thermal and/or chemical treatments, and drying methods. Commercial and laboratory isolates with different functionalities resulting from their structural modifications were compared. Isolates with high solubility or excessive thermally induced insolubilization or compact calcium-induced aggregates caused low water-imbibing capacity (WIC) values. The highest WIC results from the balance between intermediate solubility and the formation of aggregates with good hydration properties. The apparent viscosity of dispersions of commercial (spray dried) and laboratory (lyophilized) isolates depends on the WIC, the morphology and size of the particles, and the interaction of the hydrated particles. The hydration properties and viscosity of protein isolate suspensions were strongly determined by the amount and properties of the insoluble fraction.

Calorimetry, Differential Scanning↗
PubMed2006

Influence of carrier on the performance of dry powder inhalers.

The aim of this work is to study carriers which can become alternatives to monohydrate lactose in dry powder inhalers and to consider particle parameters that influence adhesion between drug and carrier in dry powder inhalers. Different forms of mannitol, lactose and maltitol were mixed with either terbutaline sulphate or formoterol fumarate. The blends were submitted to different adhesion tests where drug detachment from the carrier was obtained either through mechanical vibration or by aspiration. Parameters like particle shape, roughness, amorphous content and cristalline form may affect interactions between drug and carrier. In our case, crystallized forms of the carrier offered lower adhesion but better release of the active ingredient than spray-dried forms. The crystallized mannitol produced maximal fine particle dose. The blends of the mannitols and the two active ingredients gave different results. The two techniques used to assess the adhesion of drugs to carrier particles provide complementary information about drug/carrier interactions and detachment. The mechanical sieving allows to assess blend stability and the air-jet sieving makes it possible to determine how easily the drug separates from carrier. For the drugs tested, the results of fine particle doses are in agreement with the Alpine air-jet sieve results. The tests used are helpful for the choice of a new carrier in the field of the development of new carriers for dry powder inhalers.

Adhesiveness↗
PubMed2005

Preparation of two-drug composite microparticles to improve the dissolution of insoluble drug in water for use with a 4-fluid nozzle spray drier.

In this study, we used a novel 4-fluid nozzle spray drier to prepare composite microparticles of a water-insoluble drug, flurbiprofen (FP), and a water-soluble drug, sodium salicylate (SS), for the purpose of improving the water solubility of FP. An ethanol solution of FP and an aqueous SS solution were simultaneously introduced through different liquid passages in the 4-fluid nozzle spray drier and then spray-dried. Quantitative elemental analysis suggested that the FP/SS ratio in each composite microparticle was nearly the same as the formulation ratio. We also found that SS and FP exist in a low crystallinity state in the composite particles. Release of FP from dissolved composite microparticles was markedly improved because of an increase in the effective surface area following rapid dissolution of SS. This study shows that it is possible to prepare FP-SS composite microparticles using a 4-fluid nozzle spray drier in single process and that this can improve the ability of FP to dissolve in water.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1986

Fluidized bed film coating of an interactive powder mixture to produce microencapsulated 2-5 microns particles.

Previous work has shown an interactive (ordered) powder mixture, formed from 2-5 microns salicylic acid and a coarse spray-dried sugar, is stable when fluidized. The micronized material adheres to the carrier during fluid bed air suspension and may be film coated with a polymer. This process offers a novel method of microencapsulating very fine particulates, providing a way of manufacturing enteric-coated and sustained release microdose drug delivery systems. Different processing conditions were used in an attempt to optimize the retention of micronized model drug beneath the film. The effect of altering the following variables was investigated; polymer spray rate, addition of a third component which adhered to the binary adhesion units, and different materials of construction for the mixer used to form the interactive mixture. The microencapsulated adhesion units retained 90-95% of the micronized model drug. A statistical evaluation of the content uniformity showed that a very uniform dispersion was formed (CV less than 5%, 99% confidence). Multilayer film-coated adhesion units were also produced using a sequence of mixing and coating operations. This process offers a method of film coating microdose quantities of a drug, to produce a free flowing product, possessing excellent content uniformity.

Capsules↗
PubMed2005

EXUBERA: pharmaceutical development of a novel product for pulmonary delivery of insulin.

Development of a product for pulmonary delivery of insulin presented significant technology challenges for this first-in-class pharmaceutical product. These included developing (a) a chemically stabilized protein, (b) a dry powder formulation exhibiting required aerosol physical characteristics, (c) low-dose powder filling and packaging technology, and (d) a mechanical device for powder dispersal and reliable dosing to the patient. The insulin drug is formulated using a novel excipient combination to create a powder with a high glass transition temperature (Tg). The high Tg minimizes insulin mobility (thus reactivity), enabling ambient storage conditions. The formulation composition results in minimal hygroscopicity, where customized packaging produced product ruggedness to humidity. The formulated insulin powder is manufactured by spray-drying. This technology was further engineered to produce the desired reproducible powder characteristics with tight control over particle size and moisture content. A solution step prior to drying assures homogeneity and minimizes dependence on the physical form of the components. Novel low-dose filling and packaging technology reproducibly meters milligram quantities of microfine powder to meet stringent quality requirements for dose control. The technology for accurate, uniform, high-throughput metering of drug powders allows for automation and is scaleable for commercial operations. Finally, the mechanical device design provides powder deagglomeration and dispersion processes in a reusable dry powder inhaler with unique characteristics. The device was designed to rely on patient-generated compressed air as the energy source. A sonic discharge of air through the novel TransJector reproducibly extracts, deagglomerates, and disperses the inhalation powder. A clear holding (spacer-type) chamber allows for patient feedback via dose visualization, and separates powder dispersal from the inspiratory effort. The EXUBERA [Pfizer (New York, NY) and sanofi-aventis (Paris, France)] product provides insulin into the bloodstream with similar reproducibly and effectiveness as subcutaneous injections.

Administration, Inhalation↗
PubMed2003

In-situ-micronization of disodium cromoglycate for pulmonary delivery.

Drug particle properties are critical for the therapeutic efficiency of a drug delivered to the lung. Jet-milling, a commonly used technique for micronization of drugs, has several disadvantages such as a non-homogeneous particle size distribution, and unnatural, thermodynamically activated particle surfaces causing high agglomeration. For pulmonary use in a dry powder inhaler, in addition to a small particle size, good de-agglomeration behaviour is required. In this study disodium cromoglycate is prepared in situ in a respirable particle size by a controlled crystallization technique. First the drug is dissolved in water (4%) and precipitated by a solvent change method in the presence of a cellulose ether (hydroxypropylmethylcellulose) as a stabilizing hydrocolloid. By rapidly pouring isopropyl alcohol into the drug solution in a 1:8 (v/v) ratio, the previously molecularly dispersed drug is associated to small particles and stabilized against crystal growth in the presence of the hydrophilic polymer. This dispersion was spray-dried. The mean particle size of the drug was around 3.5 microm and consequently was in the respirable range. The in-situ-micronized drug powder was tested for its aerodynamic behaviour and compared with jet-milled drug powder and with commercial products using the Spinhaler, the Cyclohaler, and the FlowCaps-Inhaler as model devices. The fine particle fraction (FPF) (<5 microm) was increased from 7% for the jet-milled drug to approximately 75% for the in-situ-micronized drug when the pure drug powder was dispersed without any device. Delivery of the engineered particles via the Spinhaler, the FlowCaps-Inhaler and the Cyclohaler increased the FPF from 11 to 46%, 19 to 51%, and 8 to 40%, respectively.

Administration, Inhalation↗