Formulation and in vivo evaluation of sodium alendronate spray-dried microparticles intended for lung delivery

Cruz, Letícia; Fattal, Elias; Tasso, Leandro; Freitas, Gabrielle Coelho; Carregaro, Adriano Bonfim; Guterres, Sílvia Stanisçuaski; Pohlmann, Adriana Raffin

doi:10.1016/j.jconrel.2011.02.030

Cited by 47 publications

(30 citation statements)

References 35 publications

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“…aerosol performance parameters are often reported, FPF% values for porous poly(lactic-co-glycolic acid) particles were reported to be in the range of 10.7%-33.8% 5 and sodium alendronate from 34.4% to 62.0%. 38 The novel findings reported here indicate the significant potential of these lipopolymeric lung surfactant-mimic particles to be utilized to effectively deliver many different types of therapeutics to the lung as inhaled dry powder nanomedicine aerosols.…”

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confidence: 83%

“…2,8,14,36 Spray-drying has been used in the microencapsulation of bioactive molecules, as well as in the preparation of drug-delivery systems composed of a large variety of biodegradable polymers and excipients. [37][38][39] It has also been used as a scalable method in the bulk preparation of drug-lipid mixtures. 37,40,41 The unique features and tunable parameters of spray-drying allow for the precise tuning of the particle properties as a result of rational design and engineering.…”

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confidence: 99%

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Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols

Meenach¹,

Vogt²,

Anderson³

et al. 2013

IJN

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Novel advanced spray-dried and co-spray-dried inhalable lung surfactant-mimic phospholipid and poly(ethylene glycol) (PEG)ylated lipopolymers as microparticulate/ nanoparticulate dry powders of biodegradable biocompatible lipopolymers were rationally formulated via an organic solution advanced spray-drying process in closed mode using various phospholipid formulations and rationally chosen spray-drying pump rates. Ratios of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine PEG (DPPE-PEG) with varying PEG lengths were mixed in a dilute methanol solution. Scanning electron microscopy images showed the smooth, spherical particle morphology of the inhalable particles. The size of the particles was statistically analyzed using the scanning electron micrographs and SigmaScan ® software and were determined to be 600 nm to 1.2 µm in diameter, which is optimal for deep-lung alveolar penetration. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) were performed to analyze solid-state transitions and long-range molecular order, respectively, and allowed for the confirmation of the presence of phospholipid bilayers in the solid state of the particles. The residual water content of the particles was very low, as quantified analytically via Karl Fischer titration. The composition of the particles was confirmed using attenuated total-reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy and confocal Raman microscopy (CRM), and chemical imaging confirmed the chemical homogeneity of the particles. The dry powder aerosol dispersion properties were evaluated using the Next Generation Impactor™ (NGI™) coupled with the HandiHaler ® dry powder inhaler device, where the mass median aerodynamic diameter from 2.6 to 4.3 µm with excellent aerosol dispersion performance, as exemplified by high values of emitted dose, fine particle fraction, and respirable fraction. Overall, it was determined that the pump rates defined in the spray-drying process had a significant effect on the solid-state particle properties and that a higher pump rate produced the most optimal system. Advanced dry powder inhalers of inhalable lipopolymers for targeted dry powder inhalation delivery were successfully achieved. Dovepresssubmit your manuscript | www.dovepress.com

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confidence: 83%

mentioning

confidence: 99%

Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols

Meenach¹,

Vogt²,

Anderson³

et al. 2013

IJN

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“…This decrease in aggregation can be explained by the surface roughness, which decreases the forces existing between the particles. 16,45 Earlier studies of dexamethasone encapsulation showed that changes in particle size distribution can be due to particle aggregation, such that both the mean and median sizes increased steeply as more dexamethasone was incorporated into the formulation, with the size increase being greater at higher dexamethasone concentrations. 29 The zeta potential for all formulations was found to be negative, from -48 to -35 mV, with the zeta potential becoming less negative as the concentration of methylprednisolone increased, possibly because of the contribution to neutrality provided by the active principle.…”

Section: Encapsulation Efficiency For Methylprednisolonementioning

confidence: 99%

“…14 One of the most original techniques used in the preparation of microparticles is spray-drying, 15 which has the advantages of being able to be adapted for production on an industrial scale as well as an ability to encapsulate a range of hydrosoluble 16 and liposoluble (either sensitive or thermoresistant) substances. 17 The features of the final product, including moisture, particle size, and production yield, are determined by the physicochemical characteristics of the microparticles, as well as by factors such as feed rate, temperature, air flow, and aspirator.…”

Section: Introductionmentioning

confidence: 99%

Development of biodegradable methylprednisolone microparticles for treatment of articular pathology using a spray-drying technique

Tobar-Grande¹,

Godoy²,

Bustos³

et al. 2013

IJN

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Abstract:In this work, microparticles were prepared by spray-drying using albumin, chondroitin sulfate, and hyaluronic acid as excipients to create a controlled-release methylprednisolone system for use in inflammatory disorders such as arthritis. Scanning electron microscopy demonstrated that these microparticles were almost spherical, with development of surface wrinkling as the methylprednisolone load in the formulation was increased. The methylprednisolone load also had a direct influence on the mean diameter and zeta potential of the microparticles. Interactions between formulation excipients and the active drug were evaluated by x-ray diffraction, differential scanning calorimetry, and thermal gravimetric analysis, showing limited amounts of methylprednisolone in a crystalline state in the loaded microparticles. The encapsulation efficiency of methylprednisolone was approximately 89% in all formulations. The rate of methylprednisolone release from the microparticles depended on the initial drug load in the formulation. In vitro cytotoxic evaluation using THP-1 cells showed that none of the formulations prepared triggered an inflammatory response on release of interleukin-1β, nor did they affect cellular viability, except for the 9.1% methylprednisolone formulation, which was the maximum test concentration used. The microparticles developed in this study have characteristics amenable to a therapeutic role in inflammatory pathology, such as arthritis.

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“…Drug administration by the pulmonary route, intended for local or systemic treatment, has been the focus of many studies over the past two decades (15)(16)(17). The lungs have a high-alveolar surface area for drug absorption without hepatic first-pass metabolism, also increasing the high amount of drug in the lungs and lowering the metabolism (15,(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Development of Novel Chitosan Microcapsules for Pulmonary Delivery of Dapsone: Characterization, Aerosol Performance, and In Vivo Toxicity Evaluation

et al. 2015

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ABSTRACT. Pneumocystis carinii pneumonia (PCP) is a major opportunistic infection that affects patients with human immunodeficiency virus. Although orally administered dapsone leads to high hepatic metabolism, decreasing the therapeutic index and causing severe side effects, this drug is an effective alternative for the treatment of PCP. In this context, microencapsulation for pulmonary administration can offer an alternative to increase the bioavailability of dapsone, reducing its adverse effects. The aim of this work was to develop novel dapsone-loaded chitosan microcapsules intended for deep-lung aerosolized drug delivery. The geometric particle size (D 4,3 ) was approximately 7 μm, the calculated aerodynamic diameter (d aero ) was approximately 4.5 μm, and the mass median aerodynamic diameter from an Andersen cascade impactor was 4.7 μm. The in vitro dissolution profile showed an efficient dapsone encapsulation, demonstrating the sustained release of the drug. The in vitro deposition (measured by the Andersen cascade impactor) showed an adequate distribution and a high fine particles fraction (FPF= 50%). Scanning electron microscopy of the pulmonary tissues demonstrated an adequate deposition of these particles in the deepest part of the lung. An in vivo toxicity experiment showed the low toxicity of the drug-loaded microcapsules, indicating a protective effect of the microencapsulation process when the particles are microencapsulated. In conclusion, the pulmonary administration of the novel dapsone-loaded microcapsules could be a promising alternative for PCP treatment.

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Formulation and in vivo evaluation of sodium alendronate spray-dried microparticles intended for lung delivery

Cited by 47 publications

References 35 publications

Development of biodegradable methylprednisolone microparticles for treatment of articular pathology using a spray-drying technique

Development of Novel Chitosan Microcapsules for Pulmonary Delivery of Dapsone: Characterization, Aerosol Performance, and In Vivo Toxicity Evaluation

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