title: Nano-salbutamol dry powder inhalation: a new approach for treating broncho-constrictive conditions.
abstract: Nanoparticle DPI is known to have deeper lung penetration but its clinical utility as a potentially better treatment option needs to be evaluated in the light of higher expected mucociliary movement of the nanoparticles compared to micronized DPI. The objective of this study was to make nano-salbutamol sulphate (SBS) DPI, radiolabel it with Tc-99m using a novel surface labeling methodology, characterize the formulation and assess its in vitro and in vivo deposition in healthy human volunteers to estimate its bioavailability in the target area. Nano-SBS with a mean particle of 60.71+/-35.99 nm was produced using liquid anti-solvent precipitation method. The drug particles were spherical, pure and crystalline. Anderson cascade impaction showed that blend formulations of Nano-SBS exhibited significantly higher respirable fraction of 45.2% compared to the known behavior of micronized salbutamol sulphate blends. Though the particle size tended to increase due to solid phase interaction after blending with lactose, there was definitive correlation between the radiolabeled and non-radiolabeled forms. In 10 healthy volunteers, lower oropharyngeal depositions (25.3+/-4.5%) were observed with nano-SBS formulation compared to micronized SBS formulation (58.4+/-6.1%). Furthermore, Nano-SBS formulations showed nearly 2.3-fold increase in total lung deposition compared to micronized SBS. The in vivo deposition data and the ratio of peripheral to central lung deposition (P/C) of 1.12+/-0.4 indicate that Nano-SBS is evenly distributed within different lung regions. As demonstrated for SBS, nano-sizing may enhance regional deposition and thus provide an attractive particle engineering option for the development of blend formulations for inhalation delivery.
authors.affiliation: Department of Pharmaceutics, Hamdard University, New Delhi, India.
authors.lastname: Bhavna
authors.forename: Farhan Jalees
authors.initials: FJ
authors.lastname: Ahmad
authors.forename: Gaurav
authors.initials: G
authors.lastname: Mittal
authors.forename: Gaurav K
authors.initials: GK
authors.lastname: Jain
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
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D005260:Female; D006801:Humans; D007785:Lactose / Q000737:chemistry; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders; D019275:Radiopharmaceuticals / Q000737:chemistry; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; D005079:Excipients; D011208:Powders; D019275:Radiopharmaceuticals; D013667:Technetium; D007785:Lactose; D000420:Albuterol