Nano‐in‐Micro Sildenafil Dry Powder Formulations for the Treatment of Pulmonary Arterial Hypertension Disorders: The Synergic Effect of POxylated Polyurea Dendrimers, PLGA, and Cholesterol

2020 ◽  
Vol 37 (6) ◽  
pp. 1900447 ◽  
Author(s):  
Rita B. Restani ◽  
Rita F. Pires ◽  
Pedro V. Baptista ◽  
Alexandra R. Fernandes ◽  
Teresa Casimiro ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Synergic Effect ◽  
Dry Powder ◽  
Pulmonary Arterial ◽  
Dry Powder Formulations

scholarly journals Pharmacokinetics and tolerability of LIQ861, a novel dry-powder formulation of treprostinil

2020 ◽  
Vol 10 (4) ◽  
pp. 204589402097150
Author(s):  
Robert Roscigno ◽  
Toby Vaughn ◽  
Stephanie Anderson ◽  
William Wargin ◽  
Thomas Hunt ◽  
...  
Keyword(s):  
Single Dose ◽  
Pulmonary Arterial Hypertension ◽  
Adverse Events ◽  
Arterial Hypertension ◽  
Phase 1 ◽  
Dose Range ◽  
Dry Powder ◽  
Serious Adverse Events ◽  
Study Drug Administration ◽  
Pulmonary Arterial

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.

scholarly journals Impact of human behavior on inspiratory flow profiles in patients with pulmonary arterial hypertension using AOS™ dry powder inhaler device

2021 ◽  
Vol 11 (1) ◽  
pp. 204589402098534
Author(s):  
Sandeep Sahay ◽  
Royanne Holy ◽  
Shirley Lyons ◽  
Edwin Parsley ◽  
Mari Maurer ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Respiratory Muscle ◽  
Dry Powder Inhaler ◽  
Inspiratory Flow ◽  
Dry Powder Inhalers ◽  
Respiratory Muscle Strength ◽  
Dry Powder ◽  
Flow Profiles ◽  
Pulmonary Arterial

Relative to healthy subjects, patients with pulmonary arterial hypertension often present with decreased respiratory muscle strength, resulting in decreased maximum inspiratory pressure. Little is known about the impact of reduced respiratory muscle strength on the ability to achieve the peak inspiratory pressures needed for effective drug delivery when using portable dry powder inhalers (≥1.0 kPa). The objective of this study was to assess the impact of inhaler resistance and patient instruction on the inspiratory flow profiles of pulmonary arterial hypertension patients when using breath-actuated dry powder inhalers. The inspiratory flow profiles of 35 patients with pulmonary arterial hypertension were measured with variants of the RS01 dry powder inhaler. Profiles were determined with a custom inspiratory flow profile recorder. Results showed that going from the low resistance RS01 dry powder inhaler to the high resistance AOS® dry powder inhaler led to increases in mean peak inspiratory pressures for pulmonary arterial hypertension subjects from 3.7 kPa to 6.5 kPa. Instructions that ask pulmonary arterial hypertension subjects to inhale with maximal effort until their lungs are full led to a mean peak inspiratory pressures of 6.0 kPa versus 2.1 kPa when the same subjects are asked to inhale comfortably. Significant decreases in mean peak inspiratory pressures are also observed with decreases in lung function, with a mean peak inspiratory pressures of 7.2 kPa for subjects with FEV1 > 60% predicted, versus 3.3 kPa for those subjects with FEV1 < 50% predicted. In conclusion, despite having reduced respiratory muscle strength, subjects with pulmonary arterial hypertension can effectively use a breath-actuated dry powder inhaler. The probability of achieving effective dose delivery may be increased by using dry powder inhalers with increased device resistance, particularly when subjects do not follow the prescribed instructions and inhale comfortably.

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