The Penn State Research Foundation

Other

Massachusetts Institute of Technology

Zambon S.p.a.

Civitas Therapeutics, Inc.

Chiesi Farmaceutici S.p.a.

Alkermes, Inc.

Advanced Inhalation Research, Inc.

Eratech S.r.l.

Zambon Group

Giovanni Caponetti

Jeffrey S Hrkach

Robert Samuel Langer

David A Edwards

Justin Scot Hanes

Noah Lotan

Abdellaziz Ben-Jebria

Richard P Batycky

Loretta Maggi

Michael M Lipp

Paolo Ventura

Elliot Ehrich

Wen-I Li

Mei-Ling Pan

Karen Fu

Jason Summa

Cristina Veneziani

Laura Zanellotti

Mariko Childs

Paolo Colombo

Ruggero Bettini

Abdell Aziz Ben-Jebria

Pier Luigi Catellani

Marco Sardina

Franco Castegini

Michael W Lipp

Robert William Clarke

Paolo Corvi Mora

Sujit K Basu

Katharina J Elbert

Heike Butti

Gianluigi Faiella

Daniela Rebolini

Mariella Artusi

Robert Clarke

Eliot Ehrich

Wen-I Ki

Robert Clark

The present invention relates to inhalation formulations of drugs in the form of dry powder for inhalation administration deliverable as such with an inhaler and provided with high deliverability, respirability and stability. In particular, the invention relates to a pharmaceutical composition for inhalation in the form of powder comprising at least a first and a second powder, in which at least said first powder contains an active agent in an amount greater than 1% by weight with respect to the weight of said first powder. Both the powders comprise leucine in an amount ranging from 5 to 70% by weight with respect to the weight of each powder and a sugar in an amount ranging from 20 to 90% by weight with respect to the weight of each powder. The composition has a fine particle fraction (FPF) greater than 60% and a delivered fraction (DF) greater than 80.

Composition comprising at least two dry powders obtained by spray drying to increase the stability of the formulation

The present invention relates to inhalation formulations of drugs in the form of dry powder for inhalation administration deliverable as such with an inhaler and provided with high deliverability, respirability and stability. In particular, the invention relates to a pharmaceutical composition for inhalation use in powder form comprising a first powder comprising at least a powder (a1) comprising an active agent or a pharmaceutically acceptable salt thereof, in an amount greater than 1% by weight of the powder, leucine in an amount from 5 to 70% by weight of said powder, a sugar in an amount from 20 to 90% by weight of the powder; and a second powder comprising a mixture of a first lactose which has an X50 from 35 to 75 &#x3bc;m, with a second lactose which has an X50 from 1.5 to 10 &#x3bc;m, the content of the first and second lactose in the mixture are respectively from 85% to 96% and from 4% to 15%. The ratio by weight between the first powder and the second powder is from 1/5 to 1/100, and the composition has a fine particle fraction (FPF) greater than 60% and a delivered fraction (DF) greater than 85%.

Composition comprising at least one dry powder obtained by spray drying to increase the stability of the formulation

The present invention relates to inhalation formulations of drugs in the form of dry powder for inhalation administration, suitable for the treatment of obstructive diseases of the airways, such as asthma and chronic obstructive pulmonary disease (COPD). In particular, the invention relates to a pharmaceutical composition for inhalation comprising a first powder comprising budesonide or a pharmaceutically acceptable salt thereof, in an amount greater than 5% by weight of said first powder, leucine in an amount from 5 to 70% by weight of said first powder, lactose in an amount from 20 to 90% by weight of said first powder; a second powder comprising formoterol or a pharmaceutically acceptable salt thereof, in an amount greater than 1% by weight of said second powder, leucine in an amount from 5 to 70% by weight of said second powder, lactose in an amount from 20 to 90% by weight of said second powder and a third powder comprising a mixture of a first lactose which has an X50 from 35 to 75 &#x3bc;m, with a second lactose which has an X50 from 1.5 to 10 &#x3bc;m, the content of said first and second lactose in said mixture being respectively from 85% to 96% and from 4% to 15%. Said composition has a fine particle fraction (FPF) greater than 60% and a delivered fraction (DF) greater than 80%.

Pharmaceutical composition containing budesonide and formoterol

The present invention relates to drug formulations in dry powder form for administration by inhalation and indicated for the treatment of obstructive airway syndromes such as asthma and chronic obstructive pulmonary disease (COPD). In particular, the invention relates to an inhalable pharmaceutical composition comprising a first powder consisting of budesonide, or one of its pharmaceutically allowable salts, in a quantity greater than 5% w/w of said first powder, leucine in a quantity in the range of 5 to 70% w/w of said first powder, and lactose in a quantity in the range of 20 to 90% w/w of said first powder; a second powder consisting of formoterol, or one of its pharmaceutically allowable salts, in a quantity greater than 1% w/w of said second powder, leucine in a quantity in the range of 5 to 70% w/w of said second powder, and lactose in a quantity in the range of 20 to 90% w/w of said second powder; and a third powder consisting of leucine in a quantity in the range of 5 to 70% w/w of said third powder, and lactose in a quantity in the range of 20 to 90% w/w of said third powder. Said composition has a fine particle fraction (FPF) greater than 60% and a delivered fraction (DF) greater than 90%.

Provided is an inhalatory pharmaceutical composition that comprises a drug, a soluble excipient and a surfactant, wherein the soluble excipient is present in an amount between 10% and less than 100% by weight; and the solid excipient forms a solid matrix in which the drug is dispersed; the weight ratio between the surfactant and drug is between 0.01 and 10; the particle size of at least 50% of the particles of the powder is below 5 &#x3bc;m; the bulk density dof the powder is between 0.1 and 0.3 g/cc; the tapped density dof the powder is between 0.15 and 0.7 g/cc and the ratio d/dis between 0.2 and 0.65. Also provided is the method for fabricating the composition.

Inhalatory pharmaceutical compositions in form of dry powders, solutions or suspensions obtained from the same and process for their preparation

The present invention is directed toward particles for delivery of epinephrine to the respiratory system and methods for treating a patient in need of epinephrine. The particles and respirable compositions comprising the particles of the present invention described herein comprise the bioactive agent epinephrine, or a salt thereof, as a therapeutic agent. The particles are preferably formed by spray drying. Preferably, the particles and the respirable compositions are substantially dry and are substantially free of propellents. In a preferred embodiment, the particles have aerodynamic characteristics that permit targeted delivery of epinephrine to the site(s) of action.

Inhalable epinephrine

Pharmaceutical composition in a dry powder form comprising at least one hydrophobic active principle, at least one water-soluble excipient and at least one surfactant, wherein the particles in said dry powder state have a Volume Mean Diameter VMDgreater than the Volume Mean Diameter VMDof particles in a suspension obtained from said pharmaceutical composition at standard conditions of dispersion in a water-medium. It is also disclosed a process to prepare such dry composition and an extemporaneous suspension for inhalation therapy obtainable from said dry composition.

Dry powder pharmaceutical compositions comprising surfactants, hydrophobic active principles, and water-soluble excipients, process of preparing, and stable aqueous suspensions thereof

Particles having a tap density less than about 0.4 g/cm3 are formed by spray drying from a colloidal solution including a carboxylic acid or salt thereof, a phospholipid, a divalent salt and a solvent such as an aqueous-organic solvent. The colloidal solution can also include a therapeutic, prophylactic or diagnostic agent. Preferred carboxylic acids include at least two carboxyl groups. Preferred phospholipids include phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols, phophstidylserines, phosphatidylinositols and combinations thereof. The particles are suitable for pulmonary delivery.

Formulations for spray-drying large porous particles

The present invention is based, in part, on the unexpected discovery that particles for pulmonary delivery of a therapeutic, prophylactic or diagnostic agent that comprise a phospholipid and a sufficient amount of leucine can produce sustained effect of the agent. Specifically, particles for pulmonary delivery of a therapeutic, prophylactic or diagnostic agent that contain a phospholipid or combination of phospholipids, wherein the phospholipid or combination of phospholipids is present in the particles in an amount of about 1 to 46 weight percent; and leucine, wherein leucine is present in the particles in an amount of at least 46 weight percent, can contribute to sustained effect of the agent. Particles that comprise at least 46 weight percent leucine but that do not contain phospholipids do not exhibit these same sustained effect properties.

Inhalable sustained therapeutic formulations

Improved porous particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the porous particles are made of a biodegradable material and have a mass density less than 0.4 g/cm/. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear a-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, porous particles having a relatively large mean diameter, for example greater than 5 &#x3bc;m, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung. The porous particles incorporating a therapeutic agent may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of therapeutic agents.

Porous particles comprising excipients for deep lung delivery

Carrier particles, for use in the preparation of powdery mixtures for administration by inhalation, and having a median diameter of greater than 90 microns and a surface rugosity expressed as the fractal dimension of less than or equal to 1.1, may be prepared by subjecting particles having a median diameter of greater than 90 microns to repeated stages of wetting with a solvent and drying.

Powder particles with smooth surface for use in inhalation therapy

Formulation for spray-drying large porous particles

Improved aerodynamically light particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of biodegradable material and have a tap density of less than 0.4 g/cmand a mass mean diameter between 5 &#x3bc;m and 30 &#x3bc;m. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear &#x3b1;-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 &#x3bc;m, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung. The aerodynamically light particles incorporating a therapeutic agent may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of therapeutic agents.

Aerodynamically light particles for pulmonary drug delivery

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Piacenza, Italy

Giovanni Caponetti