Poly (ε-caprolactone) nanocapsules for oral delivery of raloxifene: process optimization by hybrid design approach, in vitro and in vivo evaluation.
Raloxifene HCl (RLX), a selective oestrogen receptor modulator, has low oral bioavailability (<2%) in humans due to its poor aqueous solubility and extensive first-pass metabolism in gut. In this study, we optimised the method of preparation for poly (ε-caprolactone) (PCL) based nanocapsules of RLX by double emulsion method (w/o/w). A hybrid design approach, Plackett-Burman design followed by rotatable central composite design, was used to arrive at the optimised formulation. The optimised formulation was subjected to in vitro and in vivo evaluation. RLX loaded nanocapsules were spherical in shape with particle size less than 200 nm and high encapsulation efficiency (>80%). RLX-loaded nanocapsules showed 2.1-fold increase in oral bioavailability compared to free RLX. IV pharmacokinetic studies indicated that RLX loaded into nanocapsule had significantly low clearance in comparison with free RLX. Designed nanocapsules showed promise as delivery systems to enhance oral bioavailability and in reducing clearance of raloxifene.
Department of Pharmacy, BITS-Pilani Hyderabad Campus , Hyderabad, Andhra Pradesh , India.
N
N
Aditya
Punna Rao
PR
Ravi
Uday Sai Ranjan
US
Avula
Rahul
R
Vats
D000284:Administration, Oral; D000818:Animals; D005260:Female; D053769:Nanocapsules / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000493:pharmacokinetics
D053769:Nanocapsules; D011091:Polyesters; D020845:Selective Estrogen Receptor Modulators; C016240:polycaprolactone; D020849:Raloxifene Hydrochloride
Design of experiments; Plackett–Burman design; Raloxifene HCl; nanocapsules; oral bio-availability; poly (ε-caprolactone); rotatable central composite design