Engineering of layered, lipid-encapsulated drug nanoparticles through spray-drying.
Drug-containing nanoparticles have been synthesized through the spray-drying of submicron droplet aerosols by using matrix materials such as lipids and biopolymers. Understanding layer formation in composite nanoparticles is essential for the appropriate engineering of particle substructures. The present study developed a droplet-shrinkage model for predicting the solid-phase formation of two non-volatile solutes-stearic acid lipid and a set of drugs, by considering molecular volume and solubility. Nanoparticle formation was simulated to define the parameter space of material properties and process conditions for the formation of a layered structure with the preferential accumulation of the lipid in the outer layer. Moreover, lipid-drug demarcation diagrams representing a set of critical values of ratios of solute properties at which the two solutes precipitate simultaneously were developed. The model was validated through the preparation of stearic acid-isoniazid nanoparticles under controlled processing conditions. The developed model can guide the selection of solvents, lipids, and processing conditions such that drug loading and lipid encapsulation in composite nanoparticles are optimized.
Centre for Research in Nanotechnology and Science, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India.
Mahak
M
Sapra
Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai Mumbai, Maharashtra 400076, India.
Y S
YS
Mayya
Centre for Research in Nanotechnology and Science, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India; Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai Mumbai, Maharashtra 400076, India. Electronic address: chandra@iitb.ac.in.
Chandra
C
Venkataraman
D000096:Acetone / Q000737:chemistry; D000336:Aerosols / Q000737:chemistry; D000995:Antitubercular Agents / Q000737:chemistry*; D002616:Chemical Engineering / Q000379:methods; D002725:Chloroform / Q000737:chemistry; D003890:Desiccation; D004337:Drug Carriers; D004339:Drug Compounding / Q000379:methods*; D000431:Ethanol / Q000737:chemistry; D007538:Isoniazid / Q000737:chemistry*; D000432:Methanol / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D044367:Phase Transition; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013229:Stearic Acids / Q000737:chemistry*
D000336:Aerosols; D000995:Antitubercular Agents; D004337:Drug Carriers; D012997:Solvents; D013229:Stearic Acids; D000096:Acetone; D000431:Ethanol; C031183:stearic acid; D002725:Chloroform; D007538:Isoniazid; D000432:Methanol
Droplet-shrinkage model; Lipid-drug demarcation diagram; Nanoparticle sub-structure; Submicron droplet aerosol; Two-solute droplets