title: Bioadhesive microspheres for bioavailability enhancement of raloxifene hydrochloride: formulation and pharmacokinetic evaluation.
abstract: Raloxifene hydrochloride (R-HCl), a BCS class II drug, remains a mainstay in the prevention and pharmacologic therapy of osteoporosis. Its absolute bioavailability, however, is 2% due to poor solubility and extensive first pass metabolism. The present study describes two simultaneous approaches to improve its bioavailability, complexation of R-HCl with cyclodextrin(s), and formulation of mucoadhesive microspheres of the complex using different proportions of carbopol and HPMC. Microspheres were pale yellow in color, free-flowing, spherical, and porous in outline. The particle size ranged between 3 and 15 μm, and entrapment efficiency was found to be within 81.63% to 87.73%. A significant improvement in the solubility of R-HCl was observed, and it differed with the combination of excipients used. X-ray diffraction and differential scanning calorimetry studies revealed that enhancement in drug solubility was resulted due to a change in its crystallinity within the formulation. Microspheres possessed remarkable mucoadhesion and offered controlled drug release, lasting up to 24 h. They produced a sharp plasma concentration-time profile of R-HCl within 30 min post-administration to Wistar rats. [AUC](0-24 h) was found to be 1,722.34 ng h/ml, and it differed significantly to that of pure drug powder (318.28 ng h/ml). More than fivefold increase in AUC and more than twofold increase in MRT were observed. FT-IR studies evidenced no interaction among drug and excipients. The results of this study showed that mucoadhesive microspheres could be a viable approach to improve the pharmacokinetic profile of R-HCl.
authors.affiliation: Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
authors.forename: Ram K
authors.initials: RK
authors.lastname: Jha
authors.forename: Sanjay
authors.initials: S
authors.lastname: Tiwari
authors.forename: Brahmeshwar
authors.initials: B
authors.lastname: Mishra
mesh_terms: D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000592:standards; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008863:Microspheres; D020849:Raloxifene Hydrochloride / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000592:standards; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014014:Tissue Adhesives / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000592:standards; D014961:X-Ray Diffraction / Q000379:methods / Q000592:standards
chemical_list: D014014:Tissue Adhesives; D020849:Raloxifene Hydrochloride