Oral bioavailability enhancement of raloxifene by developing microemulsion using D-optimal mixture design: optimization and in-vivo pharmacokinetic study

Abstract

The objective of this work was to utilize a potential of microemulsion for the improvement in oral bioavailability of raloxifene hydrochloride, a BCS class-II drug with 2% bioavailability. Drug-loaded microemulsion was prepared by water titration method using Capmul MCM C8, Tween 20, and Polyethylene glycol 400 as oil, surfactant, and co-surfactant respectively. The pseudo-ternary phase diagram was constructed between oil and surfactants mixture to obtain appropriate components and their concentration ranges that result in large existence area of microemulsion. D-optimal mixture design was utilized as a statistical tool for optimization of microemulsion considering oil, S, and water as independent variables with percentage transmittance and globule size as dependent variables. The optimized formulation showed 100 ± 0.1% transmittance and 17.85 ± 2.78 nm globule size which was identically equal with the predicted values of dependent variables given by the design expert software. The optimized microemulsion showed pronounced enhancement in release rate compared to plain drug suspension following diffusion controlled release mechanism by the Higuchi model. The formulation showed zeta potential of value -5.88 ± 1.14 mV that imparts good stability to drug loaded microemulsion dispersion. Surface morphology study with transmission electron microscope showed discrete spherical nano sized globules with smooth surface. In-vivo pharmacokinetic study of optimized microemulsion formulation in Wistar rats showed 4.29-fold enhancements in bioavailability. Stability study showed adequate results for various parameters checked up to six months. These results reveal the potential of microemulsion for significant improvement in oral bioavailability of poorly soluble raloxifene hydrochloride.

Formulation, Optimization and Characterization of Ibuprofen Loaded Microemulsion System Using D-Optimal Mixture Design

“…The transmittance value (96.95%) is close to predicted values (97.57%). This result confirms the validation of the model and the efficient emulsification of the different components [24,46].…”

“…A D-optimal mixture design [24] with 3 independent variables (percent content of oil, surfactant/co-surfactant mixture, and water) was used for carrying out the optimization study.…”

A Cosmeceutical Topical Water-in-Oil Nanoemulsion of Natural Bioactives: Design of Experiment, in vitro Characterization, and in vivo Skin Performance Against UVB Irradiation-Induced Skin Damages

“… 49 As per the results of the stability study, the high stability observed with the formulated NEs is attributed to the plasticity of the interfacial film, which was maintained throughout the shelf life of NE and hindered phase separation. 50 The measured pH values of the formulated NEs were found to be appropriate for skin topical application. 24 In addition, the slightly acidic pH value observed with Vit C-loaded NE is preferable to enhance the stability of Vit C. 11 …”

Recent Applications of Mixture Designs in Beverages, Foods, and Pharmaceutical Health: A Systematic Review and Meta-Analysis

“…Used to improve solubility of poorly soluble drugs [142]; medicated chewing gums [120]; bioactive dressings [128]; or tablets [121,139], oleogels [144,145], organogels for cardiovascular diseases [118], nanoparticles with amoxicillin trihydrate and thymol [131,134], novel excipients [129,136,146] and oils mixture with salicylic acid for ointment [143] formulation; itraconazole for oral [27,127], gel with loratadine [148], tablets of metformin [130], controlled release of ketoprofen [23] and excipients with finasteride [126] formulation; emulsion formulation of vitamins [119], of aceclofenac [122], of raloxifen [135], of aprepitant [123], of catechin [28], of darunavir [117], of lopinavir [116], of butenafine hydrochloride [132], of cathepsin K inhibitor [140], of telmisartan [138], of olmesartan medoxomil [137], of bovine serum albumin [141], of nelfinavir mesylate [124], of docetaxel [125], of nutraceutical products [147] and oxidative stability avocado oil [133].…”