DEVELOPMENT AND OPTIMIZATION OF ORAL LACIDIPINE PROBILOSOMES: A BOX–BEHNKEN DESIGN-BASED STUDY
DOI:
https://doi.org/10.22159/ijap.2025v17i5.54567Keywords:
Bilosome, Probilosome, Ethanol-injection, Solubility, Lacidipine, Box-behnken designAbstract
Objective: This study aimed to enhance the oral bioavailability of lacidipine (LCDP), a drug with poor aqueous solubility, by formulating it as bilosomes and subsequently converting the optimized formulation (Bopt) into a stable probilosomal powder (PBopt) using freeze-drying.
Methods: Bilosomes of LCDP were produced using ethanol-injection method and optimized utilizing Box-Behnken design (BBD) (a quality by design approach QBD). The optimized bilosome formulation was subsequently transformed to a free-flowing probilosome powder after using the freeze-drying method. Cholesterol (CHO), the surfactant Span®60, and the bile salt sodium deoxycholate (SDC) served as independent formulation factors, while particle size (PS, nm), entrapment efficiency (EE%), and polydispersity index (PDI) were selected as dependent responses.
Results: The optimized probilosome formulation (PBopt), with the highest desirability (0.904), indicating near-optimal performance in achieving the desired formulation characteristics as suggested by BBD, demonstrated a PS of 198.3 nm, a PDI of 0.21, a zeta potential (ZP) of −25 mV, an EE% of 93.7%, and an in vitro drug release of 90.7% within 45 min, corresponding to the Bopt formula. The BBD model showed statistically significant effects (p<0.05) on EE% and PS, indicating robust optimization, while the effect on PDI was non-significant (p>0.05). Stability studies showed that the LCDP PBopt formulation maintained its relative PS and EE% for at least three months, indicating good stability attributes.
Conclusion: Bilosomes are effective nanovesicular carriers that can enhance LCDP oral bioavailability, thus overcoming the inherent drug solubility limitations. Also, the probilosome’s free-flowing powder can be easily converted into oral solid dosage forms, overcoming the drawbacks of liquid formulations. This makes LCDP’s probilosomes as a promising approach in pharmaceutical applications.
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