Dose administration maneuvers and patient care in tobramycin dry powder inhalation therapy.

The purpose of this work was to study a new dry powder inhaler (DPI) of tobramycin capable to simplify the dose administration maneuvers to maximize the cystic fibrosis (CF) patient care in antibiotic inhalation therapy. For the purpose, tobramycin/sodium stearate powder (TobraPS) having a high drug content, was produced by spray drying, characterized and the aerodynamic behavior was investigated in vitro using different RS01 DPI inhalers. The aerosols produced with 28, 56 or 112 mg of tobramycin in TobraPS powder using capsules size #3, #2 or #0 showed that there was quasi linear relationship between the amount loaded in the device and the FPD. An in vivo study in healthy human volunteers showed that 3-6 inhalation acts were requested by the volunteers to inhale 120 mg of TobraPS powder loaded in a size #0 capsule aerosolized with a prototype RS01 device, according to their capability to inhale. The amount of powder emitted at 4 kPa pressure drop at constant air flow well correlated with the in vivo emission at dynamic flow, when the same volume of air passed through the device. The novel approach for the administration of 112 mg of tobramycin in one capsule could improve the convenience and adherence of the CF patient to the antibiotic therapy.

In vivo nose-to-brain delivery of the hydrophilic antiviral ribavirin by microparticle agglomerates.

Nasal administration has been proposed as a potential approach for the delivery of drugs to the central nervous system. Ribavirin (RBV), an antiviral drug potentially useful to treat viral infections both in humans and animals, has been previously demonstrated to attain several brain compartments after nasal administration. Here, a powder formulation in the form of agglomerates comprising micronized RBV and spray-dried microparticles containing excipients with potential absorption enhancing properties, i.e. mannitol, chitosan, and α-cyclodextrin, was developed for nasal insufflation. The agglomerates were characterized for particle size, agglomeration yield, and ex vivo RBV permeation across rabbit nasal mucosa as well as delivery from an animal dry powder insufflator device. Interestingly, permeation enhancers such as chitosan and mannitol showed a lower amount of RBV permeating across the excised nasal tissue, whereas α-cyclodextrin proved to outperform the other formulations and to match the highly soluble micronized RBV powder taken as a reference. In vivo nasal administration to rats of the agglomerates containing α-cyclodextrin showed an overall higher accumulation of RBV in all the brain compartments analyzed as compared with the micronized RBV administered as such without excipient microparticles. Hence, powder agglomerates are a valuable approach to obtain a nasal formulation potentially attaining nose-to-brain delivery of drugs with minimal processing of the APIs and improvement of the technological and biopharmaceutical properties of micronized API and excipients, as they combine optimal flow properties for handling and dosing, suitable particle size for nasal deposition, high surface area for drug dissolution, and penetration enhancing properties from excipients such as cyclodextrins.

Dry powders for the inhalation of ciprofloxacin or levofloxacin combined with a mucolytic agent for cystic fibrosis patients.

OBJECTIVE: This study aimed to design and characterize an inhalable dry powder of ciprofloxacin or levofloxacin combined with the mucolytics acetylcysteine and dornase alfa for the management of pulmonary infections in patients with cystic fibrosis. METHODS: Ball milling, homogenization in isopropyl alcohol and spray drying processes were used to prepare dry powders for inhalation. Physico-chemical characteristics of the dry powders were assessed via thermogravimetric analysis, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry and scanning electron microscopy. The particle size distribution, dissolution rate and permeability across Calu-3 cell monolayers were analyzed. The aerodynamic parameters of dry powders were determined using the Andersen cascade impactor (ACI). RESULTS: After the micronization process, the particle sizes of the raw materials significantly decreased. X-ray and DSC results indicated that although ciprofloxacin showed no changes in its crystal structure, the structure of levofloxacin became amorphous after the micronization process. FT-IR spectra exhibited the characteristic peaks for ciprofloxacin and levofloxacin in all formulations. The dissolution rates of micro-homogenized and spray-dried ciprofloxacin were higher than that of untreated ciprofloxacin. ACI results showed that all formulations had a mass median aerodynamic diameter less than 5 µm; however, levofloxacin microparticles showed higher respirability than ciprofloxacin powders did. The permeability of levofloxacin was higher than those of the ciprofloxacin formulations. CONCLUSION: Together, our study showed that these methods could suitably characterize antibiotic and mucolytic-containing dry powder inhalers.

Engineered sodium hyaluronate respirable dry powders for pulmonary drug delivery.

Sodium hyaluronate (HYA) warrants attention as a material for inhalation due to its (i) therapeutic potential, (ii) utility as a formulation excipient or drug carrier, and (iii) ability to target lung inflammation and cancer. This study aimed to overcome formulation and manufacturing impediments to engineer biocompatible spray-dried HYA powders for inhalation. Novel methodology was developed to produce HYA microparticles by spray drying. Different types of surfactant were included in the formulation to improve powder respirability, which was evaluated in vitro using cascade impactors. The individual formulation components and formulated products were evaluated for their biocompatibility with A549 respiratory epithelial cells. The inclusion of stearyl surfactants, 5% w/v, produced the most respirable HYA-powders; FPF 59.0-66.3%. A trend to marginally higher respirability was observed for powders containing stearylamine>stearyl alcohol>cetostearyl alcohol. Pure HYA was biocompatible with A549 cells at all concentrations measured, but the biocompatibility of the stearyl surfactants (based on lethal concentration 50%; LC50) in the MTT assay ranked stearyl alcohol>cetostearyl alcohol>stearylamine with LC50 of 24.7, 13.2 and 1.8µg/mL, respectively. We report the first respirable HYA powders produced by spray-drying. A lead formulation containing 5% stearyl alcohol was identified for further studies aimed at translating the proposed benefits of inhaled HYA into safe and clinically effective HYA products.

Accessorized DPI: a Shortcut towards Flexibility and Patient Adaptability in Dry Powder Inhalation.

PURPOSE: In this work, a novel powder dispersion add-on device, the AOS (Axial Oscillating Sphere), was studied in conjunction with commercially available DPI devices to improve the powder dispersion. METHODS: An ordered mixture of formoterol fumarate and lactose was selected. We studied in two laboratories located at different altitudes the dispensing and dispersion of the drug at different flow rates, paying particular attention to a number of metrics of Fine Particle Dose (FPD). RESULTS: Two novel findings emerged from the data collected. First, the aerosol quality, measured as fine particle dose, can be increased by adding the accessory promoting the dispersion and de-aggregation of the formulation. The second finding was that, albeit the emitted dose was independent of altitude, the drug/lactose carrier DPI aerosolizing performance changed with the altitude of testing. In particular, fine particle dose depended on both altitude and device configuration. The RS01 inhaler without the AOS accessory used at higher altitude gave the lowest FPD values. By combining the AOS accessory with the DPI, however, the performance dependence on altitude/atmospheric pressure was essentially removed. CONCLUSIONS: Increasing inhaler performance can be achieved using an add-on accessory that enhances aerosol dispersion and minimizes flow rate dependency.

Solid Lipid Nanoparticle assemblies (SLNas) for an anti-TB inhalation treatment-A Design of Experiments approach to investigate the influence of pre-freezing conditions on the powder respirability.

For direct intramacrophagic antitubercular therapy, pulmonary administration through Dry Powder Inhaler (DPI) devices is a reasonable option. For the achievement of efficacious aerosolisation, rifampicin-loaded Solid Lipid Nanoparticle assemblies (SLNas) were developed using the melt emulsifying technique followed by freeze-drying. Indeed, this drying method can cause freezing or drying stresses compromising powder respirability. It is the aim of this research to offer novel information regarding pre-freezing variables. These included type and concentration of cryoprotectants, pre-freezing temperature, and nanoparticle concentration in the suspension. In particular, the effects of such variables were observed at two main levels. First of all, on SLNas characteristics - i.e., size, polydispersity index, zeta-potential, circularity, density, and drug loading. Secondly, on powder respirability, taking into account aerodynamic diameter, emitted dose, and respirable fraction. Considering the complexity of the factors involved in a successful respirable powder, a Design of Experiments (DoE) approach was adopted as a statistical tool for evaluating the effect of pre-freezing conditions. Interestingly, the most favourable impact on powder respirability was exerted by quick-freezing combined with a certain grade of sample dilution before the pre-freezing step without the use of cryoprotectants. In such conditions, a very high SLNas respirable fraction (>50%) was achieved, along with acceptable yields in the final dry powder as well as a reduction of powder mass to be introduced into DPI capsules with benefits in terms of administered drug dose feasibility.

Combinations of colistin solutions and nebulisers for lung infection management in cystic fibrosis patients.

In this work different nebulisers were investigated in order to assess their efficiency in combination with colistimethate sodium (CMS) inhalation products. Four nebulisers, namely I-neb(®), Aeroneb(®) Go, eFlow(®)rapid and PARI LC(®) Sprint were studied in terms of delivered dose (DD), drug delivery rate (DDR) and respirable dose (RD) of CMS. The goal was to provide scientific data to physicians for prescribing the most appropriate nebuliser for the CMS specific user. All the apparatuses nebulised ColiFin 1MIU/3 ml solution (80 mg of CMS) with delivered doses between 31% and 41% of the loaded amount. Aeroneb Go showed the longest nebulisation time (more than 20 min). When ColiFin 2 MIU/4 ml was nebulised with eFlow rapid or PARI LC Sprint, the CMS respirable dose was 45.3mg and 39.2mg, in times of 5.6 and 10.8 min, respectively. I-neb, having a medication cup capacity limited to 0.4 ml, loaded with Promixin 0.4 MIU/0.4 ml (32 mg of CMS), provided in a time of 9 min a RD of 21.5mg, a value slightly higher than those obtained by nebulising ColiFin 1 MIU/3 ml with the other nebulisers (range 15.9-17.6 mg). The results illustrate that the clinical outcome depends on the comparative analysis of nebulisation efficiency (respirable dose) and convenience (time), not disregarding the ratios between the amount loaded, delivered and deposited at lung level.

Hyaluronate nanoparticles included in polymer films for the prolonged release of vitamin E for the management of skin wounds.

Lecithin and hyaluronic acid were used for the preparation of polysaccharide decorated nanoparticles loaded with vitamin E using the cationic lipid dioctadecyldimethylammonium bromide (DODMA). Nanoparticles showed mean particle size in the range 130-350 nm and narrow size distribution. Vitamin E encapsulation efficiency was higher than 99%. These nanoparticles were incorporated in polymeric films containing Aloe vera extract, hyaluronic acid, sodium alginate, polyethyleneoxide (PEO) and polyvinylalcohol (PVA) as an innovative treatment in skin wounds. Films were thin, flexible, resistant and suitable for application on burn wounds. Additionally, in vitro occlusion study highlighted the dependence of the occlusive effect on the presence of nanoparticles. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of skin wounds, such as burns. The controlled release of the vitamin along with a reduction in water loss through damaged skin provided by the nanoparticle-loaded polymer film are considered important features for an improvement in wound healing and skin regeneration.

Multivariate Analysis of Effects of Asthmatic Patient Respiratory Profiles on the In Vitro Performance of a Reservoir Multidose and a Capsule-Based Dry Powder Inhaler.

PURPOSE: The aim of this work was to evaluate the effect of two different dry powder inhalers, of the NGI induction port and Alberta throat and of the actual inspiratory profiles of asthmatic patients on in-vitro drug inhalation performances. METHODS: The two devices considered were a reservoir multidose and a capsule-based inhaler. The formulation used to test the inhalers was a combination of formoterol fumarate and beclomethasone dipropionate. A breath simulator was used to mimic inhalatory patterns previously determined in vivo. A multivariate approach was adopted to estimate the significance of the effect of the investigated variables in the explored domain. RESULTS: Breath simulator was a useful tool to mimic in vitro the in vivo inspiratory profiles of asthmatic patients. The type of throat coupled with the impactor did not affect the aerodynamic distribution of the investigated formulation. However, the type of inhaler and inspiratory profiles affected the respirable dose of drugs. CONCLUSIONS: The multivariate statistical approach demonstrated that the multidose inhaler, released efficiently a high fine particle mass independently from the inspiratory profiles adopted. Differently, the single dose capsule inhaler, showed a significant decrease of fine particle mass of both drugs when the device was activated using the minimum inspiratory volume (592 mL).

Effect of Flow Rate on In Vitro Aerodynamic Performance of NEXThaler(®) in Comparison with Diskus(®) and Turbohaler(®) Dry Powder Inhalers.

BACKGROUND: European and United States Pharmacopoeia compendial procedures for assessing the in vitro emitted dose and aerodynamic size distribution of a dry powder inhaler require that 4.0 L of air at a pressure drop of 4 kPa be drawn through the inhaler. However, the product performance should be investigated using conditions more representative of what is achievable by the patient population. This work compares the delivered dose and the drug deposition profile at different flow rates (30, 40, 60, and 90 L/min) of Foster NEXThaler(®) (beclomethasone dipropionate/formoterol fumarate), Seretide(®) Diskus(®) (fluticasone propionate/salmeterol xinafoate), and Symbicort(®) Turbohaler(®) (budesonide/formoterol fumarate). METHODS: The delivered dose uniformity was tested using a dose unit sampling apparatus (DUSA) at inhalation volumes either 2.0 or 4.0 L and flow rates 30, 40, 60, or 90 L/min. The aerodynamic assessment was carried out using a Next Generation Impactor by discharging each inhaler at 30, 40, 60, or 90 L/min for a time sufficient to obtain an air volume of 4 L. RESULTS: Foster(®) NEXThaler(®) and Seretide(®) Diskus(®) showed a consistent dose delivery for both the drugs included in the formulation, independently of the applied flow rate. Contrary, Symbicort(®) Turbohaler(®) showed a high decrease of the emitted dose for both budesonide and formoterol fumarate when the device was operated at airflow rate lower that 60 L/min. The aerosolizing performance of NEXThaler(®) and Diskus(®) was unaffected by the flow rate applied. Turbohaler(®) proved to be the inhaler most sensitive to changes in flow rate in terms of fine particle fraction (FPF) for both components. Among the combinations tested, Foster NEXThaler(®) was the only one capable to deliver around 50% of extra-fine particles relative to delivered dose. CONCLUSIONS: NEXThaler(®) and Diskus(®) were substantially unaffected by flow rate through the inhaler in terms of both delivered dose and fine particle mass.

"Pierce and inhale" design in capsule based dry powder inhalers: Effect of capsule piercing and motion on aerodynamic performance of drugs.

In this work three capsule-based dry powder inhalers, available for generics product development, were compared. Two technologically different dry powder formulations were used in order to relate the capsule piercing position and motion in the device to their aerodynamic performance. A "pierce and inhale" design, in which the capsules pierced with RS01, HandiHaler or Turbospin devices were aerosolized in the same device or transferred and aerosolized with another device, was constructed and carried out. The results obtained showed that two dry powder formulations, i.e., a drug/lactose blend or a carrier-free powder, aerosolized using capsule based inhalers, performed differently. The aerosolization of drug carrier mixture in terms of drug dispersion and emitted dose, was more sensible to the piercing and device combination than the carrier free powder. The motion of the capsule during the aerosolization boosted the powder emission, whereas the powder disaggregation was more influenced by the airflow pattern around the capsule and inside the inhaler turbulence chamber.

Spray-dried amikacin sulphate powder for inhalation in cystic fibrosis patients: The role of ethanol in particle formation.

A Central Composite Design (CCD) was applied in order to identify positive combinations of the production parameters of amikacin sulphate spray-dried powders for inhalation, with the intent to expand the experimental space defined in a previous half-fractional factorial design. Three factors, namely drying temperature, feed rate and ethanol proportion, have been selected out of the initial five. In addition, the levels of these factors were increased from two to three and their effect on amikacin respirability was evaluated. In particular, focus was given on the role of ethanol presence on the formation of the microparticles for inhalation. The overall outcome of the CCD was that amikacin respirability was not substantially improved, as the optimum region coincided with areas already explored with the fractional factorial design. However, expanding the design space towards smaller ethanol levels, including its complete absence, revealed the crucial role of this solvent on the morphology of the produced particles. Peclet number and drug solubility in the spraying solution helped to understand the formation mechanism of these amikacin sulphate spray-dried particles.

Spray dried amikacin powder for inhalation in cystic fibrosis patients: a quality by design approach for product construction.

An amikacin product for convenient and compliant inhalation in cystic fibrosis patients was constructed by spray-drying in order to produce powders of pure drug having high respirability and flowability. An experimental design was applied as a statistical tool for the characterization of amikacin spray drying process, through the establishment of mathematical relationships between six Critical Quality Attributes (CQAs) of the finished product and five Critical Process Parameters (CPPs). The surface-active excipient, PEG-32 stearate, studied for particle engineering, in general did not benefit the CQAs of the spray dried powders for inhalation. The spray drying feed solution required the inclusion of 10% (v/v) ethanol in order to reach the desired aerodynamic performance of powders. All desirable function solutions indicated that the favourable concentration of amikacin in the feed solution had to be kept at 1% w/v level. It was found that when the feed rate of the sprayed solution was raised, an increase in the drying temperature to the maximum value (160 °C) was required to maintain good powder respirability. Finally, the increase in drying temperature always led to an evident increase in emitted dose (ED) without affecting the desirable fine particle dose (FPD) values. The application of the experimental design enabled us to obtain amikacin powders with both ED and FPD, well above the regulatory and scientific references. The finished product contained only the active ingredient, which keeps low the mass to inhale for dose requirement.

Polymeric films loaded with vitamin E and aloe vera for topical application in the treatment of burn wounds.

Burns are serious traumas related to skin damage, causing extreme pain and possibly death. Natural drugs such as Aloe vera and vitamin E have been demonstrated to be beneficial in formulations for wound healing. The aim of this work is to develop and evaluate polymeric films containing Aloe vera and vitamin E to treat wounds caused by burns. Polymeric films containing different quantities of sodium alginate and polyvinyl alcohol (PVA) were characterized for their mechanical properties and drug release. The polymeric films, which were produced, were thin, flexible, resistant, and suitable for application on damaged skin, such as in burn wounds. Around 30% of vitamin E acetate was released from the polymeric films within 12 hours. The in vivo experiments with tape stripping indicated an effective accumulation in the stratum corneum when compared to a commercial cream containing the same quantity of vitamin E acetate. Vitamin E acetate was found in higher quantities in the deep layers of the stratum corneum when the film formulation was applied. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of burns.

Differences in physical chemistry and dissolution rate of solid particle aerosols from solution pressurised inhalers.

Solution composition alters the dynamics of beclomethasone diproprionate (BDP) particle formation from droplets emitted by pressurised metered dose inhalers (pMDIs). The hypothesis that differences in inhaler solutions result in different solid particle physical chemistry was tested using a suite of complementary calorimetric techniques. The atomisation of BDP-ethanol solutions from commercial HFA-pMDI produced aerodynamically-equivalent solid particle aerosols. However, differences in particle physico-chemistry (morphology and solvate/clathrate formation) were detected by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and supported by hot stage microscopy (HSM). Increasing the ethanol content of the formulation from 8 to 12% (w/w), which retards the evaporation of propellant and slows the increase in droplet surface viscosity, enhanced the likelihood of particles drying with a smooth surface. The dissolution rate of BDP from the 12% (w/w) ethanol formulation-derived particles (63% dissolved over 120 min) was reduced compared to the 8% (w/w) ethanol formulation-derived particles (86% dissolved over 120 min). The addition of 0.01% (w/w) formoterol fumarate or 1.3% (w/w) glycerol to the inhaler solution modified the particles and reduced the BDP dissolution rate further to 34% and 16% dissolved in 120 min, respectively. These data provide evidence that therapeutic aerosols from apparently similar inhaler products, including those with similar aerodynamic performance, may behave non-equivalently after deposition in the lungs.

Pure insulin highly respirable powders for inhalation.

The aim of the present research was to investigate the possibility to obtain by spray drying an insulin pulmonary powder respirable and stable at room temperature without the use of excipients. Several insulin spray-dried powders were prepared with or without the addition of excipients (mannitol, bovine serum albumin, aspartic acid) from water dispersions or from acidic aqueous solutions. Each formulation was characterized using laser diffraction, scanning electron microscopy and in vitro aerosol performance with a Turbospin DPI device. Stability was assessed by the quantification of impurities with a molecular mass greater than that of insulin (HMWP) and related proteins (A21+ORP). Insulin powders prepared without excipients from an acid solution showed a shrivelled, raisin-like shape of non-aggregated microparticles and a high respirability (FPF>65%). The optimal result with respect to respirability and stability was reached when the pH of the insulin acetic acid solution to spray dry was adjusted at pH 3.6 with ammonium hydroxide. The median volume diameter of the obtained powder was 4.04 µm, insulin content 95%, emitted dose of 89.5%, MMAD 1.79 µm and fine particle fraction of 83.6%. This powder was stable at room temperature over a period of eighteen months with respect to the content of A21+ORP. As far as the HMWP content was concerned, the powder complied with the specification limits for a period of five months. The insulin acetic powder opens up the possibility of a more effective pulmonary therapy less dependent on refrigerated storage.

Agglomerated oral dosage forms of artemisinin/ß-cyclodextrin spray-dried primary microparticles showing increased dissolution rate and bioavailability.

Artemisinin, a poorly water-soluble antimalarial drug, presents a low and erratic bioavailability upon oral administration. The aim of this work was to study an agglomerated powder dosage form for oral administration of artemisinin based on the artemisinin/ß-cyclodextrin primary microparticles. These primary microparticles were prepared by spray-drying a water-methanol solution of artemisinin/ß-cyclodextrin. ß-Cyclodextrin in spray-dried microparticles increased artemisinin water apparent solubility approximately sixfold. The thermal analysis evidenced a reduction in the enthalpy value associated with drug melting, due to the decrease in drug crystallinity. The latter was also evidenced by powder X-ray diffraction analysis, while (13)C-NMR analysis indicated the partial complexation with ß-cyclodextrin. Agglomerates obtained by sieve vibration of spray-dried artemisinin/ß-cyclodextrin primary microparticles exhibited free flowing and close packing properties compared with the non-flowing microparticulate powder. The in vitro dissolution rate determination of artemisinin from the agglomerates showed that in 10 min about 70% of drug was released from the agglomerates, whereas less than 10% of artemisinin was dissolved from raw material powder. Oral administration of agglomerates in rats yielded higher artemisinin plasma levels compared to those of pure drug. In the case of the agglomerated powder, a 3.2-fold increase in drug fraction absorbed was obtained.

Liposome sensing and monitoring by organic electrochemical transistors integrated in microfluidics.

BACKGROUND: Organic electrochemical transistors (OECTs), which are becoming more and more promising devices for applications in bioelectronics and nanomedicine, are proposed here as ideally suitable for sensing and real time monitoring of liposome-based structures. This is quite relevant since, currently, the techniques used to investigate liposomal structures, their stability in different environments as well as drug loading and delivery mechanisms, operate basically off-line and/or with pre-prepared sampling. METHODS: OECTs, based on the PEDOT:PSS conductive polymer, have been employed as sensors of liposome-based nanoparticles in electrolyte solutions to assess sensitivity and monitoring capabilities based on ion-to-electron amplified transduction. RESULTS: We demonstrate that OECTs are very efficient, reliable and sensitive devices for detecting liposome-based nanoparticles on a wide dynamic range down to 10(-5)mg/ml (with a lowest detection limit, assessed in real-time monitoring, of 10(-7)mg/ml), thus matching the needs of typical drug loading/drug delivery conditions. They are hence particularly well suited for real-time monitoring of liposomes in solution. Furthermore, OECTs are shown to sense and discriminate successive injection of different liposomes, so that they could be good candidates in quality-control assays or in the pharmaceutical industry. GENERAL SIGNIFICANCE: Drug loading and delivery by liposome-based structures is a fast growing and very promising field that will strongly benefit from real-time, highly sensitive and low cost monitoring of their dynamics in different pharma and biomedical environments, with a particular reference to the pharmaceutical and production processes, where a major issue is monitoring and measuring the formation and concentration of liposomes and the relative drug load. The demonstrated ability to sense and monitor complex bio-structures, such as liposomes, paves the way for very promising developments in biosensing and nanomedicine. This article is part of a Special Issue entitled Organic Bioelectronics-Novel Applications in Biomedicine.

Antidiuretic effect of desmopressin chimera agglomerates by nasal administration in rats.

In the present study, a nasal powder of the antidiuretic peptide desmopressin (DDAVP) formulated as chimera agglomerates was studied to improve drug bioavailability and provide a flexible drug product. Firstly, DDAVP was spray-dried along with mannitol and lecithin to produce primary microparticles capable of instantaneous dissolution in water. The chimera agglomerates were spontaneously formed by mechanically vibrating the microparticles on two stacked sieves. Agglomerate formation and strength were favored by the presence of lecithin. Drug content and dissolution rate remained unmodified after agglomeration. However, owing to the agglomerate larger size, powder flowability was greatly improved in comparison with the original microparticles, allowing accurate powder dosing into the nasal delivery device. DDAVP in vitro permeation across excised rabbit nasal mucosa from the agglomerates was significantly higher than that obtained from a commercial liquid nasal spray. In rats, intranasal DDAVP agglomerates allowed for efficient administration with almost 80% of the loaded powder emitted from the device into the animal nose. The administration of DDAVP agglomerates induced a significant reduction in urine production. Moreover, the antidiuretic effect of agglomerates did not significantly differ from the one induced by an intravenous injection of DDAVP at a ten-fold lower dose.