Enhancement of solubility and dissolution rate of poorly water soluble raloxifene using microwave induced fusion method

Payal Hasmukhlal Patil,Pratibha Ramratan Patil,Veena Sailendra Belgamwar,Sanjay Javerilal Surana

doi:10.1590/s1984-82502013000300019

Payal Hasmukhlal Patil, Pratibha Ramratan Patil + Show 2 more

Open Access

https://doi.org/10.1590/s1984-82502013000300019

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Abstract

The objective of the present work was to enhance the solubility and dissolution rate of the drug raloxifene HCl (RLX), which is poorly soluble in water. The solubility of RLX was observed to increase with increasing concentration of hydroxypropyl methylcellulose (HPMC E5 LV). The optimized ratio for preparing a solid dispersion (SD) of RLX with HPMC E5 LV using the microwave-induced fusion method was 1:5 w/w. Microwave energy was used to prepare SDs. HPMC E5 LV was used as a hydrophilic carrier to enhance the solubility and dissolution rate of RLX. After microwave treatment, the drug and hydrophilic polymer are fused together, and the drug is converted from the crystalline form into an amorphous form. This was confirmed through scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies. These results suggested that the microwave method is a simple and efficient method of preparing SDs. The solubility and dissolution rate of the SDs were increased significantly compared with pure RLX due to the surfactant and wetting properties of HPMC E5 LV and the formation of molecular dispersions of the drug in HPMC E5 LV. It was concluded that the solubility and dissolution rate of RLX are increased significantly when an SD of the drug is prepared using the microwave-induced fusion method.

Highlights

Most newly formulated chemical entities have the disadvantage of low bioavailability because their aqueous solubility and dissolution rate are low (Belgamwar et al, 2011)
Physical mixture Physical mixtures of raloxifene HCl (RLX) and HPMC E5 LV were prepared by mixing them in different ratios, from 1:1 to 1:6 w/w, using a mortar and pestle
These data suggest that the solubility is significantly enhanced in the case of the solid dispersion (SD) with an RLX:HPMC E5 LV ratio of 1:5

Summary

Introduction

Most newly formulated chemical entities have the disadvantage of low bioavailability because their aqueous solubility and dissolution rate are low (Belgamwar et al, 2011). The drug release profile must be improved as this property is crucial in oral drug bioavailability, for drugs with low gastrointestinal solubility and high permeability (Murali Mohan Babu et al, 2002; Karanth et al, 2006; Tekade et al, 2010). Many approaches have been used, such as micronization, solubilization, complexation with polymers, salt formation, using prodrugs and adding surfactants. All these methods suffer from certain limitations (Feeley et al, 1998). Amorphous systems exhibit significant solubility because of their extreme thermodynamic properties and lower energetic barriers compared with the crystalline forms (Pudipeddi et al, 2005; Belgamwar et al, 2011). A novel approach based on the use of microwave irradiation has become a recognized method (Moneghini et al, 2008; Tekade et al, 2010; Shinde et al, 2010)

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