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http://dx.doi.org/10.4333/KPS.2002.32.2.073

Preparation and Evaluation of Non-Crystalline Cefuroxime Axetil Solid Dispersion  

Woo, Jong-Soo (Department of Pharmceutical R&D, Hanmi Pharm. Co., Ltd.)
Chang, Hee-Chul (Department of Pharmceutical R&D, Hanmi Pharm. Co., Ltd.)
Lee, Chang-Hyun (Department of Pharmceutical R&D, Hanmi Pharm. Co., Ltd.)
Publication Information
Journal of Pharmaceutical Investigation / v.32, no.2, 2002 , pp. 73-80 More about this Journal
Abstract
Cefuroxime axetil is a cephalosporin antibiotic having a high activity against a wide spectrum of Grampositive and Gram-negative microorganisms. It is a cephalosporin antibiotic which exist as 2 diastereoisomers: diastereoisomer A and B. It shows polymorphism of three forms: a crystalline form having a melting point of about $180^{\circ}C$, a substantially amorphous form having a high melting point of about $135^{\circ}C$ and a substantially amorphous form having a low melting point of about 70^{\circ}C$. The crystalline form of cefuroxime axetil is slightly soluble in water because diastereoisomer A has lower solubility than B in water. Substantially amorphous form of which there are no difference in solubility between diastereoisomer A and B has better solubility than crystalline form, but it forms a thicker gel than crystalline form upon contact with an aqueous medium. Based on this reason, cefuroxime axetil is not readily absorbable in the gastrointestinal tract, rendering its bioavailability on oral administration very low. The object of this study was to develop an improved non-crystalline cefuroxime axetil composition having a high physicochemical stability and bioavailability. A non-crystalline cefuroxime axetil solid dispersant showing no peak on a Differential Scanning Calorimetry (DSC) scan is prepared by dissolving cefuroxime axetil and a surfactant in an organic solvent; suspending a water-insoluble inorganic carrier in the resulting solution; and spray drying the resulting suspension to remove the organic solvent, said solid dispersant having an enhanced dissolution and stability of cefuroxime axetil and being useful for the preparation of a pharmaceutical composition for oral administration. Tablet was formulated with this cefuroxime axetil solid dispersant, disintegrants and other ingredients. It disintegrated and dissolved easily and dynamically in dissolution medium, so showed a good dissolution profile.
Keywords
cefuroxime axetil; crystalline form; amorphous form; diastereoisomer; bioavailability;
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