Dataset Information

Development and Characterization of a Dry Powder Formulation for Anti-Tuberculosis Drug Spectinamide 1599.

ABSTRACT:

Purpose

Human tuberculosis (TB) is a global health problem that causes nearly 2 million deaths per year. Anti-TB therapy exists, but it needs to be administered as a cocktail of antibiotics for six months. This lengthy therapy results in low patient compliance and is the main reason attributable to the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis.

Methods

One alternative approach is to combine anti-TB multidrug therapy with inhalational TB therapy. The aim of this work was to develop and characterize dry powder formulations of spectinamide 1599 and ensure in vitro and in vivo delivered dose reproducibility using custom dosators.

Results

Amorphous dry powders of spectinamide 1599 were successfully spray dried with mass median aerodynamic diameter (MMAD)?=?2.32?±?0.05 ?m. The addition of L-leucine resulted in minor changes to the MMAD (1.69?±?0.35 ?m) but significantly improved the inhalable portion of spectinamide 1599 while maintaining amorphous qualities. Additionally, we were able to demonstrate reproducibility of dry powder administration in vitro and in vivo in mice.

Conclusions

The corresponding systemic drug exposure data indicates dose-dependent exposure in vivo in mice after dry powder intrapulmonary aerosol delivery in the dose range 15.4 - 32.8 mg/kg.

SUBMITTER: Stewart IE

PROVIDER: S-EPMC7851762 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Development and Characterization of a Dry Powder Formulation for Anti-Tuberculosis Drug Spectinamide 1599.

Stewart Ian E IE Lukka Pradeep B PB Liu Jiuyu J Meibohm Bernd B Gonzalez-Juarrero Mercedes M Braunstein Miriam S MS Lee Richard E RE Hickey Anthony J AJ

Pharmaceutical research 20190718 9

<h4>Purpose</h4>Human tuberculosis (TB) is a global health problem that causes nearly 2 million deaths per year. Anti-TB therapy exists, but it needs to be administered as a cocktail of antibiotics for six months. This lengthy therapy results in low patient compliance and is the main reason attributable to the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis.<h4>Methods</h4>One alternative approach is to combine anti-TB multidrug t ...[more]

PMID: 31321552

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Project description:A dry-powder inhaled formulation of treprostinil (LIQ861) produced using PRINT® technology offers a substantial advantage over current nebulized therapy. Treprostinil is a synthetic prostacyclin analogue that is currently approved for inhalation administration to patients with pulmonary arterial hypertension via nebulized Tyvaso® inhalation solution. LTI-101 was a phase 1, placebo-controlled, double-blind, randomized, single-center study that evaluated the ascending single-dose pharmacokinetics of LIQ861 in healthy subjects. Six sequential, escalating doses (25, 50, 75, 100, 125, and 150?mcg) were studied to investigate treprostinil exposure from LIQ861 inhalation. Subjects (n?=?57) were randomly assigned in a 3:1 ratio to receive a single dose of either LIQ861 (n?=?43) or placebo (n?=?14); 56 subjects completed all protocol-defined assessments. Following single-dose administration, treprostinil exposure from LIQ861 increased proportionally across the dose range studied, and the pharmacokinetics profile of treprostinil administered as LIQ861 was similar to prior reports of inhaled treprostinil. All doses of LIQ861 were generally well-tolerated with no deaths, serious adverse events, or dose-limiting toxicities. The most frequently reported treatment-emergent adverse events related to study drug administration were coughing and throat irritation, which are common to dry-powder formulations. Treatment-related treatment-emergent adverse events were reported more frequently at higher dose levels; however, all were assessed as mild in severity. We conclude that the pharmacokinetics profile of treprostinil using a dry-powder inhaled formulation increased in proportion to dose as anticipated and was similar to earlier reports of inhaled, nebulized treprostinil (Tyvaso®). Based on these results, a phase 3 study (INSPIRE; Clinicaltrials.gov Identifier NCT03399604) evaluating the long-term safety and tolerability of LIQ861 in patients with pulmonary arterial hypertension was initiated.

Dataset Information

Development and Characterization of a Dry Powder Formulation for Anti-Tuberculosis Drug Spectinamide 1599.

Purpose

Methods

Results

Conclusions

Publications

Development and Characterization of a Dry Powder Formulation for Anti-Tuberculosis Drug Spectinamide 1599.

Similar Datasets

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