Spray drying as an approach for enhancement of dissolution and bioavailability of Raloxifene hydrochloride.
Keywords:
Dissolution enhancement, Bioavailability, Spray drying, roloxifene, poorly soluble drugAbstract
The present study investigated the effect of spray drying raloxifene HCl (RHCL) with different classes of hydrophilic carriers (different grades of polyvinyl pyrrolidones) and cellulosic polymers) in order to determine the potential effect on dissolution rate and bioavailability of RHCL. Preformulation studies were conducted to select the appropriate carriers and drug:carrier ratio for preparing the spray dried compositions.The solid state interactions of the spray dried mixtures were evaluated by DSC & XRD. Preformulation studies revealed that amorphous compositions of RHCL could be obtained only with Plasdones (K12, K29/32 and S630). DSC studies showed that the crystalline nature of RHCL was significantly reduced on spray drying. Significant enhancement in dissolution rate was observed with the prepared spray dried compositions and out of the three grades of Plasdone, Plasdone K12 demonstrated the maximum enhancement in rate of release of RHCL. The pharmacokinetics of spray dried composition (1:1 RHCL: K12) and pure RHCL was evaluated following oral administration (25 mg/kg) in healthy female Sprague Dawley rats. The extent of the mean plasma exposures of RHCL was 7-fold higher in animals treated with spray dried mixture of RHCL, K12 (1:1) compared to animals treated with RHCL. Spray drying of RHCL with Plasdones, especially Plasdone K12, reduced drug crystallinity, increased the rate and extent of dissolution, and improved bioavailability..
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