title: Formulation, preclinical and clinical evaluation of a new submicronic arginine respiratory fluid for treatment of chronic obstructive pulmonary disorder.
abstract: Inhalational drugs often suffer from low pulmonary deposition due to their micronized size. Aim of present study was development and evaluation of a novel submicronic L-arginine respiratory fluid formulation for treatment of cardiopulmonary complications associated with chronic obstructive pulmonary disorder (COPD). Objectives were (a) to develop and characterize submicronic L-arginine respiratory fluid formulation, (b) pre-clinical safety/toxicity study in 2-animal species, (c) in vitro and in vivo evaluation in terms of respiratory fraction, and (d) clinical study to assess safety/efficacy in healthy volunteers/COPD patients. Formulation was optimized on the basis of particle size of aerosolized medication with particle size in the range of 400-500 nm. Anderson cascade impaction (ACI) studies were performed to validate the advantage in terms of respirable fraction, which indicated a high respirable fraction (51.61 ± 3.28) for the developed formulation. In vivo pulmonary deposition pattern of optimized formulation was studied using gamma scintigraphy in human volunteers using (99m)Tc-arginine as radiotracer. It clearly demonstrated a significant pulmonary deposition of the submicronic formulation in various lung compartments. Efficacy of the developed formulation was further assessed in COPD patients (n = 15) by evaluating its effect on various cardiopulmonary parameters (spirometry, pulse-oxymetry, echocardiography and 6-min walk test). A marked improvement was seen in patients after inhalation of submicronic arginine in terms of their cardiopulmonary status. Results suggest that submicronic arginine respiratory fluid has the potential to be developed into an attractive therapeutic option for treating COPD associated cardiopulmonary complications.
authors.affiliation: Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi 110054, India.
authors.forename: Virendra Pratap Singh
authors.initials: VP
authors.lastname: Rathor
authors.affiliation: Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi 110054, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Chugh
authors.affiliation: Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi 110054, India.
authors.forename: Rashid
authors.initials: R
authors.lastname: Ali
authors.affiliation: Rajanbabu Institute of Pulmonary Medicine and Tuberculosis, Kingsway Camp, Delhi 110009, India.
authors.forename: Anuj
authors.initials: A
authors.lastname: Bhatnagar
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Syed Ehtaishamul
authors.initials: SE
authors.lastname: Haque
authors.affiliation: Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi 110054, India.
authors.forename: Aseem
authors.initials: A
authors.lastname: Bhatnagar
authors.affiliation: Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi 110054, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Mittal
keywords: Chronic obstructive pulmonary disease; Gamma scintigraphy; Nebulization; Submicronic L-arginine