title: Development and clinical trial of nano-atropine sulfate dry powder inhaler as a novel organophosphorous poisoning antidote.
abstract: The aim of the work was to develop, characterize, and carry out a clinical trial with nano-atropine sulfate (nano-AS) dry powder inhaler (DPI), because this route may offer several advantages over the conventional intramuscular route as an emergency treatment, including ease of administration and more rapid bioavailability. Different batches of nanoparticles of AS were produced using variants of nanoprecipitation method. The influence of the process parameters, such as the types and quantity of solvent and nonsolvent, the stirring speed, the solvent-to-nonsolvent volume ratio, and the drug concentration, was investigated. The methodology resulted in optimally sized particles. Bulk properties of the particles made by the chosen methodology were evaluated. A clinical trial was conducted in six healthy individuals using a single DPI capsule containing 6 mg nano-AS DPI in lactose. Early blood bioavailability and atropinization pattern confirmed its value as a potential replacement to parenteral atropine in field conditions. The formulation seems to have the advantage of early therapeutic drug concentration in blood due to absorption through the lungs as well as sustained action due to absorption from the gut of the remaining portion of the drug.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutics, Hamdard University, New Delhi, India.
authors.forename: Raisuddin
authors.initials: R
authors.lastname: Ali
authors.forename: Gaurav K
authors.initials: GK
authors.lastname: Jain
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Iqbal
authors.forename: Sushma
authors.initials: S
authors.lastname: Talegaonkar
authors.forename: Pragati
authors.initials: P
authors.lastname: Pandit
authors.forename: Sunita
authors.initials: S
authors.lastname: Sule
authors.forename: Geena
authors.initials: G
authors.lastname: Malhotra
authors.forename: Roop K
authors.initials: RK
authors.lastname: Khar
authors.forename: Aseem
authors.initials: A
authors.lastname: Bhatnagar
authors.forename: Farhan J
authors.initials: FJ
authors.lastname: Ahmad
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D001285:Atropine / Q000008:administration & dosage* / Q000627:therapeutic use*; D002152:Calorimetry, Differential Scanning; D006801:Humans; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use; D062025:Organophosphate Poisoning; D010316:Particle Size; D011041:Poisoning / Q000188:drug therapy*; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D055815:Young Adult
chemical_list: D001285:Atropine