Development of USP Apparatus 3 Dissolution Method with IVIVC for Extended Release Tablets of Metformin Hydrochloride and Development of a Generic Formulation

Mendes, Thamara de Carvalho; Simon, Alice; Menezes, Jaqueline Correia Villaça; Pinto, Enrico; Cabral, Lúcio Mendes; Sousa, Valéria Pereira de

doi:10.1248/cpb.c18-00579

Cited by 10 publications

(2 citation statements)

References 29 publications

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“…According to the Biopharmaceutical Classification System (BCS), metformin is a highly hydrophilic drug and is classified as class 3, with high solubility and low permeability. It has a pKa value of 11.5, log P is -1.43, and it ionizes at physiological pH (9).…”

Section: Introductionmentioning

confidence: 99%

Dissolution Test of Patent and Generic Drugs of Metformin Hydrochloride

Torres-Moreno,

Luque-Ortega,

Torres-Moreno

et al. 2024

Dissolut. Technol.

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Type 2 diabetes is a chronic, multifactorial disease with a genetic predisposition caused by a deficit in the action or secretion of insulin, resulting in hyperglycemia, which is characterized by increased blood glucose levels. Metformin hydrochloride is the most frequently used medication. There is a wide variety of generic metformin products in the Mexican market, and these products can vary in quality depending on the manufacturing process and formulation. The purpose of this study was to assess the dissolution properties of 850-mg immediaterelease metformin hydrochloride tablets from two batches of three different brands available in the Mexican market (in Mexico City): patent Dabex, interchangeable/generic Dinorax, and similar Setebaid. In vitro dissolution studies were performed in accordance with the Pharmacopoeia of the United Mexican States (FEUM). For the titration test, Dinorax exceeded the specifications (95-105%) as well as batch 2 of the Setebaid brand. For the dissolution tests, Dinorax and Setebaid passed but not Dabex. For weight variation, all brands were within the limits of acceptance criteria. The Dabex brand, which is considered a reference by FEUM, did not pass the dissolution test.

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Section: Introductionmentioning

confidence: 99%

Dissolution Test of Patent and Generic Drugs of Metformin Hydrochloride

Torres-Moreno,

Luque-Ortega,

Torres-Moreno

et al. 2024

Dissolut. Technol.

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“…In the biopharmaceutical classification system (BCS), MET is categorized as a class III drug with high water solubility and low permeability to the cell membrane. Its log P is −1.43 and pKa value is 11.5 [ 9 , 10 ]. The utilization of this drug through epithelial cells is limited due to its high solubility in water.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic Acid‐Coated Chitosan/Gelatin Nanoparticles as a New Strategy for Topical Delivery of Metformin in Melanoma

Ebrahimnejad,

Rezaeiroshan,

Babaei

et al. 2023

BioMed Research International

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Metformin is a multipotential compound for treating diabetes II and controlling hormonal acne and skin cancer. This study was designed to enhance metformin skin penetration in melanoma using nanoparticles containing biocompatible polymers. Formulations with various concentrations of chitosan, hyaluronic acid, and sodium tripolyphosphate were fabricated using an ionic gelation technique tailored by the Box-Behnken design. The optimal formulation was selected based on the smallest particle size and the highest entrapment efficiency (EE%) and used in ex vivo skin penetration study. In vitro antiproliferation activity and apoptotic effects of formulations were evaluated using MTT and flow cytometric assays, respectively. The optimized formulation had an average size, zeta potential, EE%, and polydispersity index of 329 ± 6.30 nm, 21.94 ± 0.05 mV, 64.71 ± 6.12 % , and 0.272 ± 0.010 , respectively. The release profile of the optimized formulation displayed a biphasic trend, characterized by an early burst release, continued by a slow and sustained release compared to free metformin. The ex vivo skin absorption exhibited 1142.5 ± 156.3 μg/cm2 of metformin deposited in the skin layers for the optimized formulation compared to 603.2 ± 93.1 μg/cm2 for the free metformin. Differential scanning calorimetry confirmed the deformation of the drug from the crystal structure to an amorphous state. The attenuated total reflection Fourier transform infrared results approved no chemical interaction between the drug and other ingredients of the formulations. According to the MTT assay, metformin in nanoformulation exhibited a higher cytotoxic effect against melanoma cancer cells than free metformin (IC50: 3.94 ± 0.57 mM vs. 7.63 ± 0.26 mM, respectively, P < 0.001 ). The results proved that the optimized formulation of metformin could efficiently decrease cell proliferation by promoting apoptosis, thus providing a promising strategy for melanoma therapy.

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