Abstract
Raloxifene hydrochloride (RLH) was formulated into a pH-modified supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) to increase drug solubility and dissolution rate. Optimal formulations of pH-modified S-SMEDDSs were developed by incorporating hydroxypropyl-cellulose-L as a precipitation inhibitor and phosphoric acid as a pH modifier (an acidifier). RLH was dissolved to greater extents by all pH-modified S-SMEDDSs compared with non-pH-modified S-SMEDDSs. In particular, phosphoric acid afforded greater drug dissolution than did the other acidifiers tested, perhaps because phosphoric acid better controlled the pH. More than 50% of the RLH was released from the pH-modified S-SMEDDS at pH 2.5 compared with only ~5% of the drug into aqueous buffer (pH 1.2 or 6.8) after dissolution of a conventional tablet. pH-modified S-SMEDDSs with a hydrophilic polymer and phosphoric acid improved the dissolution behavior of a drug exhibiting poor aqueous solubility.
Highlights
Raloxifene hydrochloride (RLH, [6-hydroxy-2-(4-hydroxyphenyl)benzo-[b]thien-3-yl][4-[2-(1piperidiny-ethoxy)-phenyl]ethanone hydrochloride]) is a second-generation selective estrogen receptor modulator [1]
Drugs released from microemulsions often precipitate because of decreased solubilities, reducing drug availability and absorption in vivo
RLH was purchased from Sampoong (Seoul, Korea), and Evista® tablets (Eli Lilly and Company, lot A574405) were purchased from a local pharmacy
Summary
Raloxifene hydrochloride (RLH, [6-hydroxy-2-(4-hydroxyphenyl)benzo-[b]thien-3-yl][4-[2-(1piperidiny-ethoxy)-phenyl]ethanone hydrochloride]) is a second-generation selective estrogen receptor modulator [1]. It acts as an estrogen agonist in bone and liver, increasing bone mineral density and reducing the levels of low-density lipoprotein-cholesterol [2,3]. A supersaturation process can maintain drug solubilization above equilibrium solubility without precipitation [9,10,11,12]. Hydrophilic polymers such as hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) can be used in SMEDDS formulations as precipitation inhibitors, forming a supersaturatable self-microemulsifying drug delivery system (S-SMEDDS)
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