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Bioadhesive Microspheres for Bioavailability Enhancement of Raloxifene Hydrochloride: Formulation and Pharmacokinetic Evaluation

  • Research Article Theme: Advanced Technologies for Oral Controlled Release Guest Editors: Michael Repka, Joseph Reo, Linda Felton, and Stephen Howard
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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.

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Acknowledgments

The first author acknowledges the financial assistance of the University Grants Commission, New Delhi, in carrying out this research work. The support of Prof. O.N. Srivastava, Department of Physics, Banaras Hindu University, is thankfully acknowledged for providing the facility of SEM.

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Authors and Affiliations

  1. Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India

    Ram K. Jha, Sanjay Tiwari & Brahmeshwar Mishra

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  1. Ram K. Jha
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  2. Sanjay Tiwari
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  3. Brahmeshwar Mishra
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Correspondence to Brahmeshwar Mishra.

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Jha, R.K., Tiwari, S. & Mishra, B. Bioadhesive Microspheres for Bioavailability Enhancement of Raloxifene Hydrochloride: Formulation and Pharmacokinetic Evaluation. AAPS PharmSciTech 12, 650–657 (2011). https://doi.org/10.1208/s12249-011-9619-9

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  • DOI: https://doi.org/10.1208/s12249-011-9619-9

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