Evaporation assisted solvent-antisolvent interaction method for
preparing ultrafine nanoparticles of poorly water soluble drugs
Raj Kumar, Prem Felix Siril*
School of Basic Sciences and Advance Material Research Centre
Indian Institute of Technology Mandi, Mandi-175005 (H.P) India.
Corresponding Author- Email: prem@iitmandi.ac.in
ABSTRACT
Poor water solubility of active pharmaceutical ingredients (APIs) in general is a
serious challenge in drug development. Drug molecules having high permeability
and low solubility are classified as class II APIs in biopharmaceutical classification
system (BCS) 1. A large number of drugs that are identified through molecular
screening programs fall under BCS class-II 2. Poor water solubility also often results
in poor bioavailability and fed-fasted variations. The problem of poor solubility can be
solved by reducing the particle size of drugs 3,4. Decreasing the particles size
increase the solubility and dissolution rate and hence the bioavailability of BCS
class-II APIs 5. Spherical nanoparticles of poor water soluble drugs (PWSD) with
particle size well below 50 nm were successfully prepared by evaporation assistaned
solvent-antisolvent interaction (EASAI) method. Pure drug nanoparticles and drug
nanoparticles that are stabilized by polymers such as polyvinyl alcohol (PVA),
polyvinyl pyrrolidone (PVP) and hydroxypropyl methyl cellulose (HPMC) were also
prepared. Effect of different experimental parameters such as concentration of drug,
concentration of different stabilizers on particle size, morphology, solubility and in
vitro drug release rate of nano-PWSDs were thoroughly investigated. Spherical
morphology of the nanoparticles was confirmed by field emission scanning electron
microscopy (FESEM) and transmission electron microcopy (TEM). The drugstabilizer interaction was probed using FTIR spectroscopy. Crystal structure and
crystallinity of the nanoparticles were studied using X-ray diffraction (XRD). Thermal
response of the drug nanoparticles was studied using differential scanning
calorimetry (DSC). Solubility of prepared drug nanoparticles and drug-stabilizer
nanoparticles was higher than the raw-drugs. In vitro dissolution studies showed that
nearly 100 % of the drug was released from drug nanoparticles and drug-stabilizes
nanoparticles in very short time when compared to the raw-drugs.
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