Hot melt extrusion as an approach to improve solubility, permeability and oral absorption of a psychoactive natural product, piperine.
OBJECTIVE
The aims of the current research project were to investigate the efficiency of various polymers to enhance the solubility and increase the systemic absorption of piperine using hot melt extrusion technology.


METHODS
Piperine 10-40% w/w and Eudragit(®) EPO/Kollidon(®) VA 64 or Soluplus(®) were mixed, and the resulting blends were extruded using a twin-screw extruder (Process 11, Thermo Fisher Scientific). Drug release profiles and piperine solubility studies of the extrudates were evaluated. A non-everted intestinal sac was employed for the most promising formulation, 10% w/w piperine/Soluplus(®) , and pure piperine to study the permeability characteristics.


RESULTS
Dissolution studies demonstrated enhancement in piperine per cent release of 10% and 20% w/w piperine/Soluplus(®) extrudates up to 95% and 74%, respectively. The solubility of 10% and 20% piperine/Soluplus(®) increased more than 160- and 45-fold in water, respectively. Furthermore, permeability studies demonstrated the enhancement in piperine absorption of 10% w/w piperine/Soluplus(®) extrudates up to 158.9 μg/5 ml compared with pure piperine at 1.3 μg/5 ml within 20 min.


CONCLUSIONS
These results demonstrated that increasing the bioavailability of piperine may be achieved as demonstrated by findings in this study.
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, 38677, USA.
Eman A
EA
Ashour
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, 38677, USA.|Pii Center for Pharmaceutical Technology, The University of Mississippi, University, MS, 38677, USA.
Soumyajit
S
Majumdar
Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, AlKharj, Saudi Arabia.
Abdulla
A
Alsheteli
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Sultan
S
Alshehri
Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, AlKharj, Saudi Arabia.
Bader
B
Alsulays
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, 38677, USA.
Xin
X
Feng
Global Development and Technical Marketing, BASF SE, Ludwigshafen, 67056, Germany.
Andreas
A
Gryczke
R&D Product Management Excipients, BASF SE, Ludwigshafen, 67056, Germany.
Karl
K
Kolter
BASF Corporation, 500 White Plains Road, Tarrytown, NY, USA.
Nigel
N
Langley
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, 38677, USA.|Pii Center for Pharmaceutical Technology, The University of Mississippi, University, MS, 38677, USA.
Michael A
MA
Repka
D000470:Alkaloids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D052117:Benzodioxoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D006358:Hot Temperature; D008297:Male; D010539:Permeability; D010880:Piperidines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols; D011109:Polymethacrylic Acids; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011145:Polyvinyls; D011205:Povidone; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014867:Water
D000470:Alkaloids; D052117:Benzodioxoles; D010880:Piperidines; D010936:Plant Extracts; D011109:Polymethacrylic Acids; D053284:Polyunsaturated Alkamides; D011145:Polyvinyls; D011619:Psychotropic Drugs; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D014867:Water; C038300:methylmethacrylate-methacrylic acid copolymer; D011092:Polyethylene Glycols; D011205:Povidone; C008922:piperine
hot melt extrusion; permeability; piperine; solubility