A novel salt of antidiabetic drug metformin resulting from a proton transfer reaction: Synthesis, characterization, crystal structure and solution studies

Ghasemi, Fatemeh; Ghasemi, Khaled; Rezvani, Ali Reza; Shokrollahi, Ardeshir; Refahi, Masoud; García-Granda, Santiago; Mendoza, Rafael

doi:10.1016/j.molstruc.2016.11.011

Cited by 18 publications

(6 citation statements)

References 42 publications

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“…Metformin hydrochloride is hydrophilic and highly soluble in water [30]. This drug readily forms hydrogen bonds with molecules such as acids and phenol [31]. The same applies to benzalkonium chloride, which is a polar compound (soluble in water).…”

Section: Resultsmentioning

confidence: 99%

Modification of Clinoptilolite with Benzalkonium Chloride as a Carrier of Metformin Hydrochloride

Putra

Kusumawati

Permadi³

2019

Asian J. Chem.

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Clinoptilolites have a limitation in the adsorption of drug molecules due to their fixed pore structure. In this study, we modified the clinoptilolite with benzalkonium chloride. The modification was carried out by stirring 1 g of NaCl activated clinoptilolite with 100 mL of benzalkonium chloride solution with a concentration of 0.5, 1, 5, 10 and 15 % at room temperature for 24 h. After filtration and drying process, benzalkonium chloride modified clinoptilolite was stirred with 100 mL of 300 mg/L metformin hydrochloride solution at room temperature for 24 h. The result of sample characterization using FTIR spectrometer, X-ray diffractometer and N2 Sorption analyzer showed that clinoptilolite modification with benzalkonium chloride and the impregnation of metformin hydrochloride proceeded well. The optimal amount of metformin hydrochloride occurred in benzalkonium chloride 1 % modified clinoptilolite.

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Section: Resultsmentioning

confidence: 99%

Modification of Clinoptilolite with Benzalkonium Chloride as a Carrier of Metformin Hydrochloride

Putra

Kusumawati

Permadi³

2019

Asian J. Chem.

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“…Metformin HCl is a hydrophilic and highly soluble drug in water [33]. This drug was found forming hydrogen bonds with hydrophilic molecules such as acids and phenols [34]. Thus, possible interactions between drug molecules and clinoptilolites are hydrophilic interactions (hydrogen bond, dipole-dipole, or dipole ion).…”

Section: Effect Of Phmentioning

confidence: 99%

The Use of Clinoptilolites as Carrier of Metformin Hydrochloride in Drug Delivery System: In Vitro Drug Release Study

Putra

Kusumawati

2018

Asian J Pharm Clin Res

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Objective: As an antidiabetic drug, metformin hydrochloride (HCl) has been well known to possess low oral bioavailability and short half-life. In this study, we prepared the drug delivery system (DDS) of metformin HCl and clinoptilolite as its carrier. The in vitro drug release profile was further investigated.Methods: DDS was made by encapsulating metformin HCl on clinoptilolite using the wet impregnation method at various pH and initial concentration of metformin HCl. Fourier transform infrared spectrometer (FTIR), X-ray diffractometer (XRD), and N2 Sorption Analyzer were used to characterize the as-synthesized DDS. Drug release study was conducted by stirring the DDS in simulated gastric fluid and simulated intestinal fluid over 12 h.Results: The encapsulation process was achieved optimally at pH 7.0 and initial concentration of metformin HCl of 300 mg/l (CLI2-300 denoted DDS). The results of FTIR and N2 sorption analyzer confirmed the existence of metformin HCl on clinoptilolites. Meanwhile, the XRD result showed that the crystallinity of clinoptilolites remained unchanged after the encapsulation process. The cumulative drug release in the simulated gastric fluid was found to be higher than that in the simulated intestinal fluid, which indicated the potent influence of pH on the release properties of the drugs. The drug release kinetics of metformin HCl from clinoptilolite was best fitted into the Korsmeyer-Peppas model with non-Fickian transport mechanism.Conclusion: We found that clinoptilolite was suitable for DDS application, particularly as a carrier of metformin HCl.

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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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A novel salt of antidiabetic drug metformin resulting from a proton transfer reaction: Synthesis, characterization, crystal structure and solution studies

Cited by 18 publications

References 42 publications

Modification of Clinoptilolite with Benzalkonium Chloride as a Carrier of Metformin Hydrochloride

Modification of Clinoptilolite with Benzalkonium Chloride as a Carrier of Metformin Hydrochloride

The Use of Clinoptilolites as Carrier of Metformin Hydrochloride in Drug Delivery System: In Vitro Drug Release Study

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

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