Enhanced Oral Bioavailability of MT-102, a New Anti-inflammatory Agent, via a Ternary Solid Dispersion Formulation
This study aimed to develop a solid dispersion (SD) of MT-102, a new anti-inflammatory agent, to improve its oral bioavailability. The ternary SD formulations of MT-102 (a poorly soluble extract of Isatis indigotica and Juglans mandshurica) were prepared using a solvent evaporation method with various drug/excipient ratios. Following that, the effectiveness of various SDs as an oral formulation of MT-102 was investigated using indirubin as a marker component. By forming SDs with hydrophilic polymers, the aqueous solubility of indirubin was significantly increased. SD-F4, containing drug, poloxamer 407 (P407), and povidone K30 (PVP K30) at a 1:2:2 weight ratio, exhibited the optimal dissolution profiles in the acidic to neutral pH range. Compared to pure MT-102 and a physical mixture, SD-F4 increased indirubin’s dissolution from MT-102 by approximately 9.86-fold and 2.21-fold, respectively. Additionally, SD-F4 caused the sticky extract to solidify, resulting in improved flowability and handling. As a result, compared to pure MT-102, the oral administration of SD-F4 significantly improved the systemic exposure of MT-102 in rats. Overall, the ternary SD formulation of MT-102 with a blended mixture of P407 and PVP K30 appeared to be effective at improving the dissolution and oral absorption of MT-102.
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MT-102 was provided by MTHERA PHARMA (Seoul, Korea). Indirubin, 6-methoxy flavone, and (2-hydroxypropyl)-β-cyclodextrin were obtained from Sigma Aldrich (St. Louis, MO, USA). Poloxamer 188 (Kolliphor®, P188), poloxamer 407 (Kolliphor®, P407), povidone K30 (Kollidon®30, PVP K30), and copovidone K28 (Kollidon® VA 64, Co-PVP) were provided by BASF-Korea (Seoul, Korea). Hydroxypropyl methyl cellulose E5 (Methocel®, HPMC E5) was obtained from Colorcon Asia Pacific PTE LTD. (Korea Branch, Suwon, Korea). Polyethylene glycol 6000 (PEG 6000) was obtained from the Daejung Chemical & Metal Co., Ltd. (Shiheung, Korea). Low-substituted hydroxypropyl cellulose (L-HPC) was purchased from Shin-Etsu (Tokyo, Japan). All the other chemicals were of analytical grade, and all the solvents were of high-performance liquid chromatography (HPLC) grade.
Bajracharya, R.; Song, J.G.; Lee, S.H.; Jeong, S.H.; Han, H.-K. Enhanced Oral Bioavailability of MT-102, a New Anti-inflammatory Agent, via a Ternary Solid Dispersion Formulation. Pharmaceutics 2022, 14, 1510. https://doi.org/10.3390/pharmaceutics14071510