Design and Development of Solid SMEDDS and Liquisolid Formulations of Lovastatin, for Improved Drug Dissolution and In vivo Effects – a Pharmacokinetic and Pharmacodynamic Assessment

Lovastatin (Lov) is a lipid-lowering agent, with 5% bioavailability (BA) due to extensive first pass metabolism and poor solubility. To enhance dissolution and in vivo effects, Lov solid self microemulsifying drug delivery system (SMEDDS) and liquisolid systems were developed and evaluated to select superior one. Solubilities were determined in oils, surfactants, and cosurfactants. Ternary phase diagrams were constructed and selected the one which showed maximum emulsion zone. In vitro dissolution, DSC, SEM and PXRD studies were used to characterize the developed formulations.

In vivo studies were conducted on optimal formulations in wistar rats. Based on solubilities, Capmul PG8 and Capmul MCM were preferred as oils, Labrasol and Transcutol P as surfactant and cosurfactant. Here, Syloid XDP carrier showed better adsorption capacity among others, hence was used in optimal solid SMEDDS (SX) and liquisolid (LS) formulations. Dissolution study results showed significant improvement in release when compared to pure drug. DSC, SEM, and PXRD results indicated the loss of drug crystallinity in optimal formulations. In pharmacokinetic (PK) study, SX and LS showed 2.57 and 1.43 fold improvements in AUC, when compared to that of coarse suspension (CS). In pharmacodynamic (PD) study, hyperlipidemia was induced by Triton X-100. CS and LS treatments showed a decline in hyperlipidemic levels at 4 h. But, SX-treated group showed early onset of decline at 2 h. Further, the duration of anti-hyperlipidemia was at least 12 h extra when compared to CS and LS. This study confirmed the superiority of SX over LS in PK and PD effects.

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Suram, D., Veerabrahma, K. Design and Development of Solid SMEDDS and Liquisolid Formulations of Lovastatin, for Improved Drug Dissolution and In vivo Effects—a Pharmacokinetic and Pharmacodynamic Assessment. AAPS PharmSciTech 23, 123 (2022). https://doi.org/10.1208/s12249-022-02272-2