Duodenum-triggered delivery of pravastatin sodium: II. Design, appraisal and pharmacokinetic assessments of enteric surface-decorated nanocubosomal dispersions.
BACKGROUND
Pravastatin sodium (PVS) is a freely water-soluble HMG-CoA inhibitor that suffers from instability at gastric pH, extensive first pass metabolism, short elimination half-life (1-3 h) and low oral bioavailability (18%).


OBJECTIVE
To overpower these drawbacks and to maximize drug absorption at its main site of absorption at the duodenum, enteric surface-coated PVS-loaded nanocubosomal dispersions were presented.


METHODS
Glyceryl monooleate (GMO)-based dispersions were developed by the fragmentation or the liquid precursor methods using Pluronic® F127 or Cremophor® EL as surfactants. As a challenging enteric-coating approach, the promising dispersions were surface-coated via lyophilization with Eudragit® L100-55; a duodenum-targeting polymer. The drug content, particle size, zeta potential, morphology and release studies of PVS-loaded dispersions were evaluated before and after surface-coating. Compared to an aqueous PVS solution, the pharmacokinetics of the best achieved system (E-F8) was evaluated (UPLC-MS/MS) in rats.


RESULTS
The enteric surface-coated nanocubosomal dispersions were more or less spherical in shape and showed high drug-loading, negative zeta potential values and fine-tuned biphasic drug-release patterns characterized by retarded (2 h) and sustained (10 h) phases in pH 1.2 and pH 6.8, respectively. E-F8 system showed significantly (p< 0.05) higher oral bioavailability, delayed Tmaxand prolonged MRT0-∞following oral administration in rats.


CONCLUSIONS
The duodenum-triggering potential and the controlled-release characteristics of the best achieved system for smart PVS delivery were revealed.
a Department of Pharmaceutics and Industrial Pharmacy , Faculty of Pharmacy, Cairo University , Cairo , Egypt.
Saadia Ahmed
SA
Tayel
a Department of Pharmaceutics and Industrial Pharmacy , Faculty of Pharmacy, Cairo University , Cairo , Egypt.
Mohamed Ahmed
MA
El-Nabarawi
a Department of Pharmaceutics and Industrial Pharmacy , Faculty of Pharmacy, Cairo University , Cairo , Egypt.
Mina Ibrahim
MI
Tadros
a Department of Pharmaceutics and Industrial Pharmacy , Faculty of Pharmacy, Cairo University , Cairo , Egypt.
Wessam Hamdy
WH
Abd-Elsalam
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D004386:Duodenum / Q000187:drug effects*; D007408:Intestinal Absorption / Q000502:physiology; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D017035:Pravastatin / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties
D003692:Delayed-Action Preparations; D011108:Polymers; D020442:Poloxamer; D017035:Pravastatin
Enteric surface-coating; fragmentation method; liquid precursor method; nanocubosomes; pravastatin sodium