Investigation of Metformin HCl Lot-to-Lot Variation on Flowability Differences Exhibited during Drug Product Processing

Vippagunta, Radha; LoBrutto, Rosario; Pan, Changkang; Lakshman, Jay P.

doi:10.1002/jps.22207

Cited by 10 publications

(4 citation statements)

References 24 publications

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“…Metformin HCl seems to be present at its thermodynamically stable form A (CSD JAMRYI01), showing predominant peaks at 12.2, 17.7, 24.42 and 37.11 (Vippagunta et al, 2010). Some of these peaks are present in HME filament and 3D printed Eudragit® RL layers, with significantly decreased intensity.…”

Section: Resultsmentioning

confidence: 99%

A 3D printed bilayer oral solid dosage form combining metformin for prolonged and glimepiride for immediate drug delivery

Gioumouxouzis

Baklavaridis

Katsamenis

et al. 2018

European Journal of Pharmaceutical Sciences

170

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Section: Resultsmentioning

confidence: 99%

A 3D printed bilayer oral solid dosage form combining metformin for prolonged and glimepiride for immediate drug delivery

Gioumouxouzis

Baklavaridis

Katsamenis

et al. 2018

European Journal of Pharmaceutical Sciences

170

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“…Metformin hydrochloride by itself has a low moisture sorption capability 20 and is a free flowing powder. However, due to its high water solubility, it is prone to make solid bridges between particles even in the presence of small amount of moisture, resulting in powder lumps or solid blocks over time.…”

Section: Powder Blendingmentioning

confidence: 99%

Investigating the Use of Polymeric Binders in Twin Screw Melt Granulation Process for Improving Compactibility of Drugs

Batra

Desai

Serajuddin

2017

Journal of Pharmaceutical Sciences

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Traditionally, the melt granulation for pharmaceutical products was performed at low temperature (<90°C) with high-shear granulators using low-melting waxy binders, and tablets produced using such granules were not amenable to large-scale manufacturing. The situation has changed in recent years by the use of twin screw extruder where the processing temperature could be increased to as high as 180°C and polymers with high T could be used as binders. In this study, different polymeric binders were screened for their suitability in improving compactibility of 2 drugs, metformin hydrochloride and acetaminophen, by twin screw melt granulation. Processing temperatures for the 2 drugs were set at 180°C and 130°C, respectively. Screw configuration, screw speed, and feed rate were optimized such that all polymeric binders used produced granules. Several hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, and methacrylate-based polymers, including Klucel EXF, Eudragit EPO, and Soluplus, demonstrated good tablet tensile strength (>2 MPa) when granules were produced using only 10% wt/wt polymer concentration. Certain polymers provided acceptable compactibility even at 5% wt/wt. Thus, twin screw melt granulation process may be used with different polymers at a wide range of temperature. Due to low excipient concentration, this granulation method is especially suitable for high-dose tablets.

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“…In our studies, we noticed some lot variation for metformin with regard to the effects on MECP2E1 transcripts. Indeed, lot variation has been noted for metformin HCl [58]. Therefore, we completed a new side-by-side experiment to study the effect of Daoy cells with metformin from the same company and catalogue number, but two different lot numbers, the new lot being referred to as Lot B, at concentrations of 1000 µM and 2000 µM for 6 and 48 h (Figure 3B).…”

Section: Metformin Regulates Mecp2 and Bdnf Transcripts In A Time-and Dose-dependent Mannermentioning

confidence: 99%

Transcriptional Regulation of MECP2E1-E2 Isoforms and BDNF by Metformin and Simvastatin through Analyzing Nascent RNA Synthesis in a Human Brain Cell Line

2021

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Methyl CpG binding protein 2 (MeCP2) is the main DNA methyl-binding protein in the brain that binds to 5-methylcytosine and 5-hydroxymethyl cytosine. MECP2 gene mutations are the main origin of Rett Syndrome (RTT), a neurodevelopmental disorder in young females. The disease has no existing cure, however, metabolic drugs such as metformin and statins have recently emerged as potential therapeutic candidates. In addition, induced MECP2-BDNF homeostasis regulation has been suggested as a therapy avenue. Here, we analyzed nascent RNA synthesis versus steady state total cellular RNA to study the transcriptional effects of metformin (an anti-diabetic drug) on MECP2 isoforms (E1 and E2) and BNDF in a human brain cell line. Additionally, we investigated the impact of simvastatin (a cholesterol lowering drug) on transcriptional regulation of MECP2E1/E2-BDNF. Metformin was capable of post-transcriptionally inducing BDNF and/or MECP2E1, while transcriptionally inhibiting MECP2E2. In contrast simvastatin significantly inhibited BDNF transcription without significantly impacting MECP2E2 transcripts. Further analysis of ribosomal RNA transcripts confirmed that the drug neither individually nor in combination affected these fundamentally important transcripts. Experimental analysis was completed in conditions of the presence or absence of serum starvation that showed minimal impact for serum deprival, although significant inhibition of steady state MECP2E1 by simvastatin was only detected in non-serum starved cells. Taken together, our results suggest that metformin controls MECP2E1/E2-BDNF transcriptionally and/or post-transcriptionally, and that simvastatin is a potent transcriptional inhibitor of BDNF. The transcriptional effect of these drugs on MECP2E1/E2-BDNF were not additive under these tested conditions, however, either drug may have potential application for related disorders.

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Investigation of Metformin HCl Lot-to-Lot Variation on Flowability Differences Exhibited during Drug Product Processing

Cited by 10 publications

References 24 publications

A 3D printed bilayer oral solid dosage form combining metformin for prolonged and glimepiride for immediate drug delivery

A 3D printed bilayer oral solid dosage form combining metformin for prolonged and glimepiride for immediate drug delivery

Investigating the Use of Polymeric Binders in Twin Screw Melt Granulation Process for Improving Compactibility of Drugs

Transcriptional Regulation of MECP2E1-E2 Isoforms and BDNF by Metformin and Simvastatin through Analyzing Nascent RNA Synthesis in a Human Brain Cell Line

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