68 Comparison of pharmacy prescription refill frequency in CF adults before and after switching from tobramycin inhalation solution (TIS) to TOBI Podhaler – ‘Real world’ evidence of improved adherence

Nash, Emma; Ahitan, B.; Brown, Colin J.; Thakrar, Kashyap; Carrolan, V.; Rashid, R.; Whitehouse, J.L.

doi:10.1016/s1569-1993(13)60210-6

Cited by 6 publications

(3 citation statements)

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“…Collectively, these benefits markedly relieve a patient’s burden of treatment. Given that preservation of lung function in persons with CF relies upon adherence to therapy, improvements in existing therapies that increase patient adherence improve therapeutic outcomes. − TOBI Podhaler is approved in nearly 70 countries worldwide.…”

Section: Introductionmentioning

confidence: 99%

Physical Characterization of Tobramycin Inhalation Powder: I. Rational Design of a Stable Engineered-Particle Formulation for Delivery to the Lungs

et al. 2015

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A spray-dried engineered particle formulation, Tobramycin Inhalation Powder (TIP), was designed through rational selection of formulation composition and process parameters. This PulmoSphere powder comprises small, porous particles with a high drug load. As a drug/device combination, TOBI Podhaler enables delivery of high doses of drug per inhalation, a feature critical for dry powder delivery of anti-infectives for treatment of cystic fibrosis. The objective of this work was to characterize TIP on both the particle and molecular levels using multiple orthogonal physical characterization techniques. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), electron spectroscopy for chemical analysis (ESCA), and Raman measurements show that a TIP particle consists of two phases: amorphous, glassy tobramycin sulfate with a glass transition temperature of about 100 °C and a gel-phase phospholipid (DSPC) with a gel-to-liquid-crystal transition temperature of about 80 °C. This was by design and constituted a rational formulation approach to provide Tg and Tm values that are well above the temperatures used for long-term storage of TIP. Raman and ESCA data provide support for a core/shell particle architecture of TIP. Particle surfaces are enriched with a porous, hydrophobic coating that reduces cohesive forces, improving powder fluidization and dispersibility. The excellent aerosol dispersibility of TIP enables highly efficient delivery of fine particles to the respiratory tract. Collectively, particle engineering has enabled development of TOBI Podhaler, an approved inhaled drug product that meaningfully reduces the treatment burden to cystic fibrosis patients worldwide.

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Section: Introductionmentioning

confidence: 99%

Physical Characterization of Tobramycin Inhalation Powder: I. Rational Design of a Stable Engineered-Particle Formulation for Delivery to the Lungs

et al. 2015

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“…Nash et al sought to determine if the ease and convenience of TIP was associated with an increased rate of prescription fill, as a surrogate measure for compliance. 112 …”

Section: Introductionmentioning

confidence: 99%

Tobramycin Inhalation Powder (TIP): An Efficient Treatment Strategy for the Management of Chronic Pseudomonas Aeruginosa Infection in Cystic Fibrosis

Lam

Vaughan

Parkins

2013

Clin Med Insights Circ Respir Pulm Med

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Repeated bouts of acute and chronic lung infections are responsible for progressive pulmonary function decline in individuals with cystic fibrosis (CF), ultimately leading to respiratory failure and death. Pseudomonas aeruginosa is the archetypical CF pathogen, causes chronic infection in 70% of individuals, and is associated with an accelerated clinical decline. The management of P. aeruginosa in CF has been revolutionized with the development and widespread use of inhaled antibiotics. Aerosol delivery of antimicrobial compounds in CF enables extremely high concentrations of antibiotics to be reached directly at the site of infection potentially overcoming adaptive resistance and avoiding the potential for cumulative systemic toxicities. Tobramycin inhalation powder (TIP) represents the first dry powder inhaled (DPI) antibiotic available for use in CF. DPIs are notable for a markedly reduced time for administration, ease of portability, and increased compliance. TIP has been developed as a therapeutic alternative to tobramycin inhalation solution (TIS), the standard of care for the past 20 years within CF. Relative to TIS 300 mg nebulized twice daily in on-and-off cycles of 28 days duration, TIP 112 mg twice daily via the T-326 inhaler administered on the same schedule is associated with marked time savings, increased patient satisfaction, and comparable clinical end points. TIP represents an innovative treatment strategy for those individuals with CF and holds the promise of increased patient compliance and thus the potential for improved clinical outcomes.

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“…Collectively, these benefits markedly reduce a patient’s burden of treatment. Given that preservation of lung function in persons with CF relies upon adherence to therapy, advances in existing therapies that increase patient adherence improve therapeutic outcomes. − TOBI Podhaler is approved in more than 70 countries worldwide.…”

Section: Introductionmentioning

confidence: 99%

Physical Characterization of Tobramycin Inhalation Powder: II. State Diagram of an Amorphous Engineered Particle Formulation

et al. 2017

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Tobramycin Inhalation Powder (TIP) is a spray-dried engineered particle formulation used in TOBI Podhaler, a drug-device combination for treatment of cystic fibrosis (CF). A TIP particle consists of two phases: amorphous, glassy tobramycin sulfate and a gel-phase phospholipid (DSPC). The objective of this work was to characterize both the amorphous and gel phases following exposure of TIP to a broad range of RH and temperature. Because, in principle, changes in either particle morphology or the solid-state form of the drug could affect drug delivery or biopharmaceutical properties, understanding physical stability was critical to development and registration of this product. Studies included morphological assessments of particles, thermal analysis to measure the gel-to-liquid crystalline phase transition (T) of the phospholipid and the glass transition temperature (T) of tobramycin sulfate, enthalpy relaxation measurements to estimate structural relaxation times, and gravimetric vapor sorption to measure moisture sorption isotherms of TIP and its components. Collectively, these data enabled development of a state diagram for TIP-a map of the environmental conditions under which physical stability can be expected. This diagram shows that, at long-term storage conditions, TIP is at least 50 °C below the T of the amorphous phase and at least 40 °C below the T of the gel phase. Enthalpy relaxation measurements demonstrate that the characteristic structural relaxation times under these storage conditions are many orders of magnitude greater than that at T. These data, along with long-term physicochemical stability studies conducted during product development, demonstrate that TIP is physically stable, remaining as a mechanical solid over time scales and conditions relevant to a pharmaceutical product. This met a key design goal in the development of TIP: a room-temperature-stable formulation (3-year shelf life) that obviates the need for refrigeration for long-term storage. This has enabled development of TOBI Podhaler-an approved inhaled drug product that meaningfully reduces the treatment burden of CF patients worldwide.

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68 Comparison of pharmacy prescription refill frequency in CF adults before and after switching from tobramycin inhalation solution (TIS) to TOBI Podhaler – ‘Real world’ evidence of improved adherence

Cited by 6 publications

References 0 publications

Physical Characterization of Tobramycin Inhalation Powder: I. Rational Design of a Stable Engineered-Particle Formulation for Delivery to the Lungs

Physical Characterization of Tobramycin Inhalation Powder: I. Rational Design of a Stable Engineered-Particle Formulation for Delivery to the Lungs

Tobramycin Inhalation Powder (TIP): An Efficient Treatment Strategy for the Management of Chronic Pseudomonas Aeruginosa Infection in Cystic Fibrosis

Physical Characterization of Tobramycin Inhalation Powder: II. State Diagram of an Amorphous Engineered Particle Formulation

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