Oral Bioavailability Enhancement and Anti-Fatigue Assessment of the Andrographolide Loaded Solid Dispersion
School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Department of Sports Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
Substance and Behavior Addiction Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(7), 2506; https://doi.org/10.3390/ijms21072506
Received: 3 March 2020 / Revised: 26 March 2020 / Accepted: 2 April 2020 / Published: 4 April 2020
(This article belongs to the Section Molecular Pharmacology)
Andrographolide (AG), a major diterpene lactone isolated from Andrographis paniculata (Burm. f.) Nees (Acanthaceae), possesses a wide spectrum of biological activities. However, its poor water solubility and low bioavailability limit its clinical application. Therefore, this study aimed to develop a solid dispersion (SD) formulation to increase the aqueous solubility and dissolution rate of AG. Different drug-polymer ratios were used to prepare various SDs. The optimized formulation was characterized for differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffraction. The analysis indicated that the optimized SD enhanced AG solubility and dissolution rates by changing AG crystallinity to an amorphous state. The dissolution behaviors of the optimum SD composed of an AG-polyvinylpyrrolidone K30-Kolliphor EL ratio of 1:7:1 (w/w/w) resulted in the highest accumulated dissolution (approximately 80%). Pharmacokinetic studies revealed that Cmax/dose and the AUC/dose increased by 3.7-fold and 3.0-fold, respectively, compared with AG suspension. Furthermore, pretreatment using the optimized AG-SD significantly increased the swimming time to exhaustion by 1.7-fold and decreased the plasma ammonia level by 71.5%, compared with the vehicle group. In conclusion, the optimized AG-SD formulation appeared to effectively improve its dissolution rate and oral bioavailability. Moreover, the optimized AG-SD provides a promising treatment against physical fatigue.