首页|Duodenum-triggered delivery of pravastatin sodium: II. Design, appraisal and pharmacokinetic assessments of enteric surface-decorated nanocubosomal dispersions
Duodenum-triggered delivery of pravastatin sodium: II. Design, appraisal and pharmacokinetic assessments of enteric surface-decorated nanocubosomal dispersions
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NSTL
Taylor & Francis
Context: 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 (1-3h) 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. Materials and methods: Glyceryl monooleate (GMO)-based dispersions were developed by the fragmentation or the liquid precursor methods using Pluronic (R) F127 or Cremophor (R) EL as surfactants. As a challenging enteric-coating approach, the promising dispersions were surface-coated via lyophilization with Eudragit (R) 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 (2h) and sustained (10h) phases in pH 1.2 and pH 6.8, respectively. E-F8 system showed significantly (p<0.05) higher oral bioavailability, delayed T-max and 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.
NSTL
Taylor & Francis
