Formulation and Evaluation of a Self-Microemulsifying Drug Delivery System of Raloxifene with Improved Solubility and Oral Bioavailability

Poor aqueous solubility and dissolution limit the oral bioavailability of Biopharmaceutics Classification System (BCS) class II drugs. In this study, we aimed to improve the aqueous solubility and oral bioavailability of raloxifene hydrochloride (RLX), a BCS class II drug, using a self-microemulsify...

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Published in:Pharmaceutics 2023-08, Vol.15 (8), p.2073
Main Authors: Ansari, Muhammad Mohsin, Vo, Dang-Khoa, Choi, Ho-Ik, Ryu, Jeong-Su, Bae, Yumi, Bukhari, Nadeem Irfan, Zeb, Alam, Kim, Jin-Ki, Maeng, Han-Joo
Format: Article
Language:English
Subjects:
Analysis
Antagonists
BCS class II
Bioavailability
Breast cancer
Calibration
dissolution
Drug delivery systems
Drugs
Estrogen
Estrogens
Football (College)
Hormone replacement therapy
Microemulsions
Nanoparticles
Oral administration
oral bioavailability
Osteoporosis
Particle size
Polyethylene glycol
Polyols
Raloxifene
raloxifene hydrochloride
SMEDDS
solubility
Surface active agents
Surfactants
Vehicles
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Summary:Poor aqueous solubility and dissolution limit the oral bioavailability of Biopharmaceutics Classification System (BCS) class II drugs. In this study, we aimed to improve the aqueous solubility and oral bioavailability of raloxifene hydrochloride (RLX), a BCS class II drug, using a self-microemulsifying drug delivery system (SMEDDS). Based on the solubilities of RLX, Capryol 90, Tween 80/Labrasol ALF, and polyethylene glycol 400 (PEG-400) were selected as the oil, surfactant mixture, and cosurfactant, respectively. Pseudo-ternary phase diagrams were constructed to determine the optimal composition (Capryol 90/Tween 80/Labrasol ALF/PEG-400 in 150/478.1/159.4/212.5 volume ratio) for RLX-SMEDDS with a small droplet size (147.1 nm) and stable microemulsification (PDI: 0.227). Differential scanning calorimetry and powder X-ray diffraction of lyophilized RLX-SMEDDS revealed the loss of crystallinity, suggesting a molecularly dissolved or amorphous state of RLX in the SMEDDS formulation. Moreover, RLX-SMEDDS exhibited significantly higher saturation solubility and dissolution rate in water, simulated gastric fluid (pH 1.2), and simulated intestinal fluid (pH 6.8) than RLX powder. Additionally, oral administration of RLX-SMEDDS to female rats resulted in 1.94- and 1.80-fold higher area under the curve and maximum plasma concentration, respectively, than the RLX dispersion. Collectively, our findings suggest SMEDDS is a promising oral formulation to enhance the therapeutic efficacy of RLX.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics15082073