ABIRATERONE ACETATE LOADED SOLID LIPID NANOPARTICLES FOR IMPROVED ORAL BIOAVAILABILITY: DESIGN OF EXPERIMENTS BASED FORMULATION OPTIMIZATION, IN-VITRO, EX-VIVO AND IN-VIVO CHARACTERIZATION

SURESH KONATHAM; SHASHIKALA PATANGAY

doi:10.22159/ijap.2023v15i2.46710

Authors

SURESH KONATHAM Osmania University Main Rd, Amberpet, Hyderabad, Telangana 500007 https://orcid.org/0000-0002-8806-3043
SHASHIKALA PATANGAY Osmania University Main Rd, Amberpet, Hyderabad, Telangana 500007

DOI:

https://doi.org/10.22159/ijap.2023v15i2.46710

Keywords:

Abiraterone acetate, Solid Lipid Nanoparticles, Sustained Release, BCS Class IV drugs, Design of Experiments

Abstract

Objective: Abiraterone acetate (AA), a BCS Class IV drug, demonstrates biopharmaceutical challenges like polymorphism, poor solubility (<0.5 μg/ml), inconsistent permeability, and low oral bioavailability (<10%) (Hence requires high dose of 1000mg/day). The current research’s main objective is to improve oral bioavailability by manufacturing AA-loaded solid lipid nanoparticles (AA-SLNs).

Methods: SLNs were manufactured using hot homogenization followed by ultra-sonication method. Initial screening of lipids (Glyceryl monostearate (GMS), Glyceryl Monooleate (GMO)), and surfactants (Tween 80 and Span 20) was done by mixture design. Based on statistical analysis, GMO and Tween 80 were selected for further optimization, and Central composite design (CCD) of experiments were done to optimize the composition using particle size, polydispersity index (PDI), encapsulation efficiency (EE), zeta potential, and cumulative % drug release as responses. Comparative ex-vivo and in-vivo evaluations of optimized formulation were done with pure drug and marketed formulation.

Results: Based on statistical evaluation, GMO - 4.4% and Tween 80 - 3.6% were optimized. Optimized AA-SLNs were found in spherical shape with size of 286.7±12.6 nm, PDI of 0.138±0.015, EE of 94.0±1.0 %, and zeta potential of -25.0±1.0 mV. Drug release from optimized formulation was extended for 24 hours, and ex-vivo permeability was increased by 2.5 and 1.42 times, whereas Relative Oral bioavailability was improved by 6.36 and 1.99 times compared to pure drug and marketed tablets, respectively.

Conclusion: The results concluded that AA-SLNs showed increased oral bioavailability compared to the pure drug and marketed formulation. Hence the dose of the formulation can be reduced to achieve desired therapeutic effect.

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