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.
Subject(s)
Chemistry, Pharmaceutical/methods , Microspheres , Raloxifene Hydrochloride/chemistry , Raloxifene Hydrochloride/pharmacokinetics , Tissue Adhesives/chemistry , Tissue Adhesives/pharmacokinetics , Animals , Biological Availability , Chemistry, Pharmaceutical/standards , Drug Evaluation, Preclinical/methods , Drug Evaluation, Preclinical/standards , Female , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Male , Raloxifene Hydrochloride/standards , Rats , Rats, Wistar , Solubility , Tissue Adhesives/standards , X-Ray Diffraction/methods , X-Ray Diffraction/standardsABSTRACT
Traumatic posterior dislocation of hip associated with ipsilateral displaced femoral neck fracture is a rare injury. Moreover, the management of such patients evokes strong views regarding primary replacement or preserving the femoral head. We presented a case of young adult with such an injury. He was operated upon with reduction of the dislocation and fixation of femoral neck fracture with the help of cancellous screws. Two years later, the fracture had united and the patient was asymptomatic. We further proposed the mechanism of injury for such a fracture and discussed the management in the changing trauma scenario of the developing world.
