152 research outputs found

    Quantifying the loading capacity of a carrier-based DPI formulation and its dependence on the blending process

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    Abstract Non-segregating ordered powder mixtures constituted by a coarse carrier fraction and finer components are at the basis of dry powders for inhalation pharmaceuticas. The estimation of the loading capacity, i.e. how many fines can be hosted on each carrier particle, is crucial to grant the product quality through a reproducible and affordable manufacturing process. We propose an approach based on the combination of sieve analysis, optical microscopy and powder bed permeability to quantify the loading capacity and understand the fines behavior, the impact of the mixing process was also investigated. We tested the method on model binary mixtures composed only of a coarse lactose carrier and micronized lactose fines as a surrogate of a real active pharmaceutical ingredient. The results provided by the different methods are consistent, the approach proved to be accurate and reproducible. The effect of different mixing parameters and equipment on the loading capacity is also discussed

    3D-printed scaffold composites for the stimuli-induced local delivery of bioactive adjuncts

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    Polysaccharide scaffolds have been successfully employed to reconstruct environments that sustain skin tissue regeneration after injuries. Three-dimensional (3D) advanced additive manufacturing technologies allow creating scaffolds with controlled and reproducible macro- and micro-structure that improve the quality of the restored tissue to favor spontaneous repair. However, when persistent inflammation occurs, the physiological tissue healing capacity is reduced, like in the presence of pathologies like diabetes, vascular diseases, chronic infection, and others. In these circumstances, the bioavailability of therapeutic adjuncts like the growth factors in addition to the standard treatments represents undoubtedly a promising strategy to accelerate the healing of skin lesions. Precisely designed polysaccharide scaffolds obtained by 3D printing represent a robust platform that can be further implemented with the controlled delivery of bioactive adjuncts. Human elastin-like polypeptides (HELPs) are stimuli-responsive biopolymers. Their structure allows the integration of domains endowed with biological functionality, making them attractive compounds to prepare composites with smart properties. In the present study, 3D-printed alginate and chitosan scaffolds were combined with the HELP components. The HELP biopolymer was fused to the epidermal growth factor (EGF) as the bioactive domain. Different constructs were prepared and the stimuli-responsive behavior as well as the biological activity were evaluated, suggesting that these smart bioactive composites are suitable to realize multifunctional dressings that sustain the local release of therapeutic adjuncts

    Dexamethasone nano-embedded sodium hyaluronate microparticles for treatment of COVID-19 acute respiratory distress syndrome

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    Dexamethasone (DX) is a synthetic glucocorticoid employed in a wide range of diseases asimmunosuppressant. Recent studies reported that DX could be administered orally or intravenouslyfor the treatment of acute respiratory distress syndrome in patients with COVID-19 phase-3infection caused by an overreaction of their immune system, reducing 28-day mortality in patientsmechanically ventilated or receiving oxygen [1]. Nevertheless, the long-term systemicadministration of dexamethasone led to severe side effects, highlighting the urgent need of newstrategies for its delivery [2][3]. The aim of this work was to develop a new formulation for inhalationbased on DX-nanoparticles. High molecular weight sodium hyaluronate (HA, 750 kDa) was employedto coat DX nanoparticles to exploit HA targeting to CD44 receptors on pulmonary macrophages andits anti-inflammatory effects[4]. DX-nanoparticles were obtained by anti-solvent precipitation usingwater as anti-solvent dripped into an alcoholic solution of drug. The suspension was spray-dried toobtain a dry powder. Size distribution and morphology of microparticles were investigated by laserdiffraction and scanning electron microscopy. Nanoparticle characteristics and composition wereassessed after powder redispersion in physiological medium by dynamic light scattering and X-rayscattering techniques. Results revealed the release of quite polydisperse nanoparticles (PdI = 0.3-0.4) with size around 290 nm in water and 180 nm in phosphate buffer. SAXS results showednanoparticles with a DX-rich crystalline core stabilized in solution by the presence of a shell of HAchains partially embedded in the core. After particle redispersion in water the aerodynamicbehavior of the obtained suspension was assessed in vitro using a device for aerosol therapyobtaining a Fine Particle Fraction of 87.5 +- 0.7% while the Emitted Fraction was 26.4 +-2.9%. Thelatter figure represents a limit that may be overcome by nebulizing directly the nanosuspension inthe pipe of a ventilator.Fil: Laura Bertocchi. Università di Parma; Italia. Departamento de Alimentos y Drogas ; Universita Degli Studi Di Parma;Fil: Cámara, Candelaria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Laura F. Cantú. Universita Degli Studi Di Milano. Dipartimento Di Beitecnologe Mediche E Medicina Traslazionale.; ItaliaFil: Elena Del Favero. Universita Degli Studi Di Milano. Dipartimento Di Beitecnologe Mediche E Medicina Traslazionale.; ItaliaFil: Ruggero Bettini. Departamento de Alimentos y Drogas ; Universita Degli Studi Di Parma;20th Advanced Course in Pharmaceutical TechnologyItaliaAssociazione Docenti e Ricercatori Italiani di Tecnologie e Legislazione Farmaceutich

    From the printer to the lungs: Inkjet-printed aerogel particles for pulmonary delivery

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    Inkjet printing is as an emerging technique in the biomedical field offering cost-effective solutions for flexible production and the engineering of personalized medicine solutions. Thermal inkjet printing technology in the “drop-on-demand” mode allows the design of fully automated deposition patterns with high spatial resolution for applications ranging from microparticles in drug formulations to cell deposition in regenerative medicine. In particular, novel formulations in the form of porous particles are sought for the treatment of respiratory disorders and the systemic administration of bioactive compounds using the pulmonary route. Aerogel particles, i.e. highly porous and light-weight nanoporous powders, are particularly promising as carriers for the pulmonary route. In this work, the preparation of aerogel microspheres by thermal inkjet printing followed by supercritical drying is presented for the first time to overcome the current processing limitations. Alginate aerogel particles were loaded with salbutamol sulphate, a bronchodilator used for the treatment of asthma attacks and chronic obstructive pulmonary disease, as a model drug for sustained pulmonary delivery. The optimized processing method allowed the preparation of reproducible nanostructured microparticles with modified salbutamol sulphate release profile and aerodynamic performance of relevance for oral inhalation purposesThis work was supported by Xunta de Galicia [grant numbers ED431F 2016/010, ED431C 2016/008] ; C.A. García-González acknowledges to MINECO for a Ramón y Cajal Fellowship [RYC2014-15239]. The authors would like to thank O’Toner Consumibles S.A. and the Technical Services Department of the USC for their valuable technical support with the selection and modifications of the inkjet cartridges and printer, respectively. Authors are also grateful to Dr. E. Solla (CACTI, Universidade de Vigo) for the technical support with the FIBSEM images.S

    Drug Release Kinetics and Front Movement in Matrix Tablets Containing Diltiazem or Metoprolol/ λ

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    In this work we investigated the moving boundaries and the associated drug release kinetics in matrix tablets prepared with two complexes between λ-carrageenan and two soluble model drugs, namely, diltiazem HCl and metoprolol tartrate aiming at clarifying the role played by drug/polymer interaction on the water uptake, swelling, drug dissolution, and drug release performance of the matrix. The two studied complexes released the drug with different mechanism indicating two different drug/polymer interaction strengths. The comparison between the drug release behaviour of the complexes and the relevant physical mixtures indicates that diltiazem gave rise to a less soluble and more stable complex with carrageenan than metoprolol. The less stable metoprolol complex afforded an erodible matrix, whereas the stronger interaction between diltiazem and carrageenan resulted in a poorly soluble, slowly dissolving matrix. It was concluded that the different stability of the studied complexes affords two distinct drug delivery systems: in the case of MTP, the dissociation of the complex, as a consequence of the interaction with water, affords a classical soluble matrix type delivery system; in the case of DTZ, the dissolving/diffusing species is the complex itself because of the very strong interaction between the drug and the polymer

    dose administration maneuvers and patient care in tobramycin dry powder inhalation therapy

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    Abstract 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

    Hyaluronic acid—dexamethasone nanoparticles for local adjunct therapy of lung inflammation

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    The delivery of a dexamethasone formulation directly into the lung appears as an appro-priate strategy to strengthen the systemic administration, reducing the dosage in the treatment of lung severe inflammations. For this purpose, a hyaluronic acid-dexamethasone formulation was developed, affording an inhalable reconstituted nanosuspension suitable to be aerosolized. The physico-chemical and biopharmaceutical properties of the formulation were tested: size, stability, loading of the spray-dried dry powder, reconstitution capability upon redispersion in aqueous me-dia. Detailed structural insights on nanoparticles after reconstitution were obtained by light and X-ray scattering techniques. (1) The size of the nanoparticles, around 200 nm, is in the proper range for a possible engulfment by macrophages. (2) Their structure is of the core-shell type, hosting dex-amethasone nanocrystals inside and carrying hyaluronic acid chains on the surface. This specific structure allows for nanosuspension stability and provides nanoparticles with muco-inert proper-ties. (3) The nanosuspension can be efficiently aerosolized, allowing for a high drug fraction poten-tially reaching the deep lung. Thus, this formulation represents a promising tool for the lung administration via nebulization directly in the pipe of ventilators, to be used as such or as adjunct therapy for severe lung inflammation.Fil: Cámara, Candelaria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Bertocchi, Laura. Departamento de Alimentos y Drogas ; Universita Degli Studi Di Parma;Fil: Ricci, Caterina. Universita Degli Studi Di Milano. Dipartimento Di Beitecnologe Mediche E Medicina Traslazionale.; ItaliaFil: Bassi, Rosaria. Universita Degli Studi Di Milano. Dipartimento Di Beitecnologe Mediche E Medicina Traslazionale.; ItaliaFil: Bianchera, Annalisa. Departamento de Alimentos y Drogas ; Universita Degli Studi Di Parma;Fil: Cantú, Laura F.. Universita Degli Studi Di Milano. Dipartimento Di Beitecnologe Mediche E Medicina Traslazionale.; ItaliaFil: Ruggero, Bettini. Departamento de Alimentos y Drogas ; Universita Degli Studi Di Parma;Fil: Del Favero, Elena. Universita Degli Studi Di Milano. Dipartimento Di Beitecnologe Mediche E Medicina Traslazionale.; Itali
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