Proliposome powders for enhanced intestinal absorption and bioavailability of raloxifene hydrochloride: effect of surface charge

Abstract

The primary goal of the present study was to investigate the combined prospective of proliposomes and surface charge for the improved oral delivery of raloxifene hydrochloride (RXH). Keeping this objective, the present systematic study was focused to formulate proliposomes by varying the ratio of hydrogenated soyphosphatidylcholine and cholesterol. Furthermore, to assess the role of surface charge on improved absorption of RXH, anionic and cationic vesicles were prepared using dicetyl phosphate and stearylamine, respectively. The formulations were characterized for size, zeta potential and entrapment efficiency. The improved dissolution characteristics assessed from dissolution efficiency, mean dissolution rate were higher for proliposome formulations. The solid state characterization studies indicate the transformation of native crystalline form of the drug to amorphous and/or molecular state. The higher effective permeability coefficient and fraction absorbed in humans extrapolated from in situ single-pass intestinal absorption study data in rats provide an insight on the potential of proliposomes and cationic surface charge for augment in absorption across gastro intestinal barrier. To draw the conclusions, in vivo pharmacokinetic study carried out in rats indicate a threefold enhancement in the rate and extent of absorption of RXH from cationic proliposome formulation which unfurl the potential of proliposomes and role of cationic charge for improved oral delivery of RXH.

Keywords::

• Proliposomes
• raloxifene hydrochloride
• surface charge
• in situ absorption
• bioavailability

Acknowledgements

The authors are grateful to Lipoid, Germany for the generous gift of Phospholipon 90H. The financial assistance to Ashok Velpula and Karthik Yadav Janga by All India Council of Technical Education (New Delhi, India) in the form of Junior Research Fellowship is duly acknowledged. The authors also thank Mr. T. Jayapal Reddy, Director, St. Peter’s Institute of Pharmaceutical Sciences for providing the necessary facilities.

Declaration of interest

The authors report no conflicts of interest.