Conjugation of Hot-Melt Extrusion with High-Pressure Homogenization: a Novel Method of Continuously Preparing Nanocrystal Solid Dispersions.
Over the past few decades, nanocrystal formulations have evolved as promising drug delivery systems owing to their ability to enhance the bioavailability and maintain the stability of poorly water-soluble drugs. However, conventional methods of preparing nanocrystal formulations, such as spray drying and freeze drying, have some drawbacks including high cost, time and energy inefficiency, traces of residual solvent, and difficulties in continuous operation. Therefore, new techniques for the production of nanocrystal formulations are necessary. The main objective of this study was to introduce a new technique for the production of nanocrystal solid dispersions (NCSDs) by combining high-pressure homogenization (HPH) and hot-melt extrusion (HME). Efavirenz (EFZ), a Biopharmaceutics Classification System class II drug, which is used for the treatment of human immunodeficiency virus (HIV) type I, was selected as the model drug for this study. A nanosuspension (NS) was first prepared by HPH using sodium lauryl sulfate (SLS) and Kollidon® 30 as a stabilizer system. The NS was then mixed with Soluplus® in the extruder barrel, and the water was removed by evaporation. The decreased particle size and crystalline state of EFZ were confirmed by scanning electron microscopy, zeta particle size analysis, and differential scanning calorimetry. The increased dissolution rate was also determined. EFZ NCSD was found to be highly stable after storage for 6 months. In summary, the conjugation of HPH with HME technology was demonstrated to be a promising novel method for the production of NCSDs.
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.
Xingyou
X
Ye
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.
Hemlata
H
Patil
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.
Xin
X
Feng
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.
Roshan V
RV
Tiwari
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.|Pharmaceutical Application Laboratory, Shin-Etsu Chemical, Co, Ltd., Totowa, New Jersey, 07512, USA.
Jiannan
J
Lu
BASF SE, Global Development and Technical Marketing, Ludwigshafen, 67056, Germany.
Andreas
A
Gryczke
BASF SE, R&D Product Management Excipients, Ludwigshafen, 67056, Germany.
Karl
K
Kolter
BASF Corporation, 500 White Plains Road, Tarrytown, New York, 10591, USA.
Nigel
N
Langley
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.|Pii Center for Pharmaceutical Technology, The University of Mississippi, University, Mississippi, 38677, USA.
Soumyajit
S
Majumdar
Department of Physics, University of Memphis, Memphis, Tennessee, 38152, USA.
Dipesh
D
Neupane
Department of Physics, University of Memphis, Memphis, Tennessee, 38152, USA.
Sanjay R
SR
Mishra
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA. marepka@olemiss.edu.|Pii Center for Pharmaceutical Technology, The University of Mississippi, University, Mississippi, 38677, USA. marepka@olemiss.edu.
Michael A
MA
Repka
D000480:Alkynes; D048588:Benzoxazines / Q000737:chemistry; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003521:Cyclopropanes; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D005612:Freeze Drying / Q000379:methods; D006358:Hot Temperature; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D013535:Suspensions / Q000737:chemistry; D014867:Water / Q000737:chemistry
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D004337:Drug Carriers; D011145:Polyvinyls; D013535:Suspensions; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D014867:Water; D011092:Polyethylene Glycols; D011205:Povidone; C098320:efavirenz
efavirenz; high-pressure homogenization; hot-melt extrusion; nanocrystal solid dispersion; nanosuspension