Enhanced Oral Bioavailability of MT-102, a New Anti-inflammatory Agent, via a Ternary Solid Dispersion Formulation

Abstract

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.

Safety Evaluation of Curcumol by a Repeated Dose 28-Day Oral Exposure Toxicity Study in Rats

“…Curcumol, a natural product isolated from the traditional Chinese medicine Rhizoma curcumae , possesses various therapeutic values for many diseases [ 19 ]. However, the low aqueous solubility of curcumol may affect drug absorption in the gastrointestinal tract of animals and further limit the translation of this drug into clinical practice [ 1 , 20 ]. In this case, we explored the dose formulation of curcumol and set up four different formulas for oral administration in rats and followed the pharmacokinetic experiments.…”

“…In recent years, extracts and active components of traditional medicine have become the focus of the pharmaceutical and food industry due to their extensive pharmacological activities and application value. Rhizoma curcumae , a traditional Chinese medicine, has been well-known for its use in alleviating pain, removing blood stasis, and anticoagulation over thousands of years [ 1 ]. The essential oil extract of Rhizoma curcumae has shown good bioactivities in anti-bacterial and anti-inflammatory properties, and has already been approved as a therapeutic remedy for disorders by the National Medical Products Administration (NMPA) of China [ 2 ].…”

“…Curcumol, a type of sesquiterpenoid isolated from Rhizoma curcumae , was a major active ingredient in its essential oil extracts and included in the quality control standards of essential oil extracts stipulated in the Chinese Pharmacopoeia. It is reported that curcumol shows great potential in anti-tumor, anti-liver fibrosis, anti-inflammatory, and anti-viral activities [ 1 , 5 , 6 , 7 , 8 , 9 , 10 ], attracting much attention on its pharmacological properties. Moreover, compared to the essential oil of Rhizoma curcumae , the quality of curcumol can be better controlled, indicating that curcumol is a promising drug candidate for clinical use.…”

Improved Therapeutic Efficacy of MT102, a New Anti-Inflammatory Agent, via a Self-Microemulsifying Drug Delivery System, in Ulcerative Colitis Mice

“…Pharmaceutics 2023, 15, x FOR PEER REVIEW 2 of 15 MT-102 is a natural extract derived from Isatis indigotica and Juglans mandshurica, exhibiting a good anti-inflammatory effect [6]. Given its poor aqueous solubility, MT-102 exhibits low oral bioavailability [6].…”

“…Pharmaceutics 2023, 15, x FOR PEER REVIEW 2 of 15 MT-102 is a natural extract derived from Isatis indigotica and Juglans mandshurica, exhibiting a good anti-inflammatory effect [6]. Given its poor aqueous solubility, MT-102 exhibits low oral bioavailability [6]. Thus, effective solubilization of MT-102 is essential for enhancing its oral efficacy.…”