Improving Dissolution and Cytotoxicity by Forming Multidrug Crystals

Bian, Xufei; Jiang, Lan; Zhou, Jing; Guan, Xiaoshu; Wang, Jingyu; Xiang, Peng; Pan, Junyi; Hu, Xiangnan

doi:10.3390/molecules25061343

Cited by 7 publications

(3 citation statements)

References 42 publications

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“…It can be seen that CEP was a bisbenzylisoquinoline alkaloid with weak base, so that it had high solubility under acidic condition (45). Additionally, several studies have shown that the absorption of weak base in the gastrointestinal tract occurs predominantly in the intestine (pH=5~7) (46,47). Whence, it is necessary to enhance the poor dissolution of CEP in the weak base medium to improve oral bioavailability.…”

Section: In Vitro Release Experimentsmentioning

confidence: 99%

Preparation and Evaluation of Self-emulsifying Drug Delivery System (SEDDS) of Cepharanthine

et al. 2021

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The aim of this article was to design a self-emulsifying drug delivery system (SEDDS) of loaded cepharanthine (CEP) to improve the oral bioavailability in rats. Based on the solubility determination and pseudo-ternary phase diagram, isopropyl palmitate (IPP) was chosen as the oil phase. Meanwhile, Cremophor RH40 and Macrogol 200 (PEG 200) were chosen as the emulsifier and co-emulsifier, respectively. This prescription was further optimized by using central composite design of response surface methodology. The optimized condition was CEP:IPP:Cremophor RH40:PEG 200=3.6:30.0:55.3:11.1 in mass ratio with maximum drug loading (36.21 mg/mL) and the minimum particle size (36.70 nm). The constructed CEP-SEDDS was characterized by dynamic light scattering, transmission electron microscopy, in vitro release and stability studies. The dissolution level of CEP-SEDDS was nearly 100% after 30 min in phosphate-buffered saline (PBS, pH 6.8) which was higher than that of the pure CEP (approximately 20%). In addition, in vivo pharmacokinetic study in rats showed that CEP-SEDDS dramatically improved bioavailability compared with active pharmaceutical ingredient (API) (the relative bioavailability was 203.46%). In this study, CEP-SEDDS was successfully prepared to enhance the oral bioavailability which might facilitate to increase its better clinical application. Graphical abstract

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Section: In Vitro Release Experimentsmentioning

confidence: 99%

Preparation and Evaluation of Self-emulsifying Drug Delivery System (SEDDS) of Cepharanthine

et al. 2021

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“…After excluding entries corresponding to the MTF base molecule and its inorganic salts (4) as well as MTF metal complexes (29), the remaining dataset contained 26 molecular salts (44%). From the remaining molecular salts, 13 entries corresponded to MTF–drug salts, mainly antidiabetic drugs [ 34 , 35 , 36 , 37 , 38 ]. Only three salt structures containing MTF and an NSAID as counterion have been reported: MTF–diclofenac [ 39 ], MTF–salicylate [ 40 ], and MTF–aspirin [ 41 ] salts.…”

Section: Resultsmentioning

confidence: 99%

Metformin-NSAIDs Molecular Salts: A Path towards Enhanced Oral Bioavailability and Stability

et al. 2023

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According to the World Health Organization, more than 422 million people worldwide have diabetes. The most common oral treatment for type 2 diabetes is the drug metformin (MTF), which is usually formulated as a hydrochloride to achieve higher water solubility. However, this drug is also highly hygroscopic, thus showing stability problems. Another kind of worldwide prescribed drug is the non-steroidal anti-inflammatory drug (NSAID). These latter, on the contrary, show a low solubility profile; therefore, they must be administered at high doses, which increases the probability of secondary effects. In this work, novel drug-drug pharmaceutical solids combining MTF-NSAIDs have been synthesized in solution or by mechanochemical methods. The aim of this concomitant treatment is to improve the physicochemical properties of the parent active pharmaceutical ingredients. After a careful solid-state characterization along with solubility and stability studies, it can be concluded that the new molecular salt formulations enhance not only the stability of MTF but also the solubility of NSAIDs, thus giving promising results regarding the development of these novel pharmaceutical multicomponent solids.

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“…Based on clinical studies, nausea, vomiting, diarrhea, and other gastrointestinal side effects occur in 20-30% of patients taking metformin hydrochloride [30]. Considering the above problems, researchers have carried out multicomponent co-crystallization studies on MET via salification strategy [6,11,[31][32][33][34][35][36][37][38][39][40][41][42]. However, these literature reports mainly focused on the optimization of MET physicochemical properties, and no pharmacological evaluation has been conducted on the hypoglycemic effect of multicomponent salts in vivo.…”

Section: Introductionmentioning

confidence: 99%

Versatile Solid Modifications of Multicomponent Pharmaceutical Salts: Novel Metformin–Rhein Salts Based on Advantage Complementary Strategy Design

Liang

et al. 2023

Pharmaceutics

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This study aimed to develop an effective treatment for diabetes and diabetic complications, based on the advantage complementary strategy of drug–drug salt, by designing and synthesizing the multicomponent molecular salts containing metformin (MET) and rhein (RHE). Finally, the salts of MET–RHE (1:1), MET–RHE–H2O (1:1:1), MET–RHE–ethanol–H2O (1:1:1:1), and MET–RHE–acetonitrile (2:2:1) were obtained, indicating the polymorphism of salts formed by MET and RHE. The structures were analyzed by the combination of characterization experiments and theoretical calculation, and the formation mechanism of polymorphism was discussed. The obtained results of in vitro evaluation showed that MET–RHE had a similar hygroscopicity with metformin hydrochloride (MET·HCl), and the solubility of the component of RHE increased by approximately 93 times, which laid a foundation for improving the bioavailability of MET and RHE in vivo. The evaluation of hypoglycemic activity in mice (C57BL/6N) indicated that MET–RHE exhibited better hypoglycemic activity than the parent drugs and the physical mixtures of MET and RHE. The above findings demonstrate that this study achieved the complementary advantages of MET and RHE through the multicomponent pharmaceutical salification technique, and provides new possibilities for the treatment of diabetic complications.

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Improving Dissolution and Cytotoxicity by Forming Multidrug Crystals

Cited by 7 publications

References 42 publications

Preparation and Evaluation of Self-emulsifying Drug Delivery System (SEDDS) of Cepharanthine

Preparation and Evaluation of Self-emulsifying Drug Delivery System (SEDDS) of Cepharanthine

Metformin-NSAIDs Molecular Salts: A Path towards Enhanced Oral Bioavailability and Stability

Versatile Solid Modifications of Multicomponent Pharmaceutical Salts: Novel Metformin–Rhein Salts Based on Advantage Complementary Strategy Design

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