Solid state compatibility study and characterization of a novel degradation product of tacrolimus in formulation

Peterka, Tanja Rozman; Grahek, Rok; Hren, Jure; Bastarda, Andrej; Bergles, Jure; Urleb, U.

doi:10.1016/j.jpba.2015.02.047

Cited by 12 publications

(11 citation statements)

References 26 publications

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“…Figure 6 depicts the 1 H NMR spectra for TAC-NMF in CDCL 3, TAC-NMF and blank-NMF in D 2 O and TAC in CDCL 3 . The spectra for TAC in CDCL 3 are in accordance with previously published results [45]. A sharp peak for oxyethylene group -CH 2 -CH 2 -O (δ = 3.8 ppm), hydroxyl protons (PEG) (δ = 4.5 ppm), and moderate signals for methylene =CH 2 (δ = 1.3 ppm) and methyl -CH 3 (δ = 0.7 ppm) groups of HCO-40 amphiphilic surfactant polymer were recorded.…”

Section: Nanomicellar Dilution Studysupporting

confidence: 91%

Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery

et al. 2020

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Neovascular age-related macular degeneration (AMD) is characterized by an increase in reactive oxygen species (ROS) and pro-inflammatory cytokines in the retinal pigment epithelium cells. The primary purpose of this study was the development of a clear, tacrolimus nanomicellar formulation (TAC-NMF) for AMD. The optimized formulation had a mean diameter of 15.41 nm, a zeta potential of 0.5 mV, and an entrapment efficiency of 97.13%. In-vitro cytotoxicity studies revealed the dose-dependent cytotoxicity of TAC-NMF on various ocular cell lines, such as human retinal pigment epithelium (D407), monkey retinal choroidal endothelial (RF/6A) cells, and human corneal epithelium (CCL 20.2) cells. Cellular uptake and in-vitro distribution studies using flow cytometry and confocal microscopy, respectively, indicated an elevated uptake of TAC-NMF in a time-dependent manner. Biocompatibility assay using macrophage RAW 264.7 cell line resulted in low production of inflammatory cytokines such as IL-6, IL-1β and TNF-α after treatment with TAC-NMF. There was a decrease in ROS in D407 cells pre-treated with sodium iodate (ROS inducing agent) after treating with TAC-NMF and tacrolimus drug. Similarly, there was a reduction in the pro-inflammatory cytokines and VEGF-A in D407 cells pretreated with sodium iodate. This indicates that TAC-NMF could lower pro-inflammatory cytokines and ROS commonly seen in AMD.

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Section: Nanomicellar Dilution Studysupporting

confidence: 91%

Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery

et al. 2020

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“…Sometimes chemical moieties of the drug can transform into degradants in presence of Magnesium stearate. There were several literature exists for the degradants formed in presence of magnesium stearate [41]- [45].…”

Section: Magnesium Stearatementioning

confidence: 99%

“…Tacrolimus is macrolide drug that is widely used as a potent immune suppressant. Tenja Rozman Peterka et al [41] reported the formation of alpha-hydroxy acid from the parent tacrolimus through Benzilic acid type rearrangement reaction in the presence of magnesium stearate (Figure 27). This reaction occurred in the presence of divalent metallic cations at higher pH values.…”

Section: Benzilic Acid Rearrangement Of Tacrolimus Due To Magnesium Smentioning

confidence: 99%

Drug-Excipient Interactions: Case Studies and Overview of Drug Degradation Pathways

Hotha¹,

Roychowdhury²,

Subramanian³

2016

AJAC

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The objective of the current research article is to provide a comprehensive review of excipients impact on the stability of the drug product and their implications during the product development. Recent developments in the understanding of the degradation pathways further impact methodologies used in the pharmaceutical industry for potential stability assessment. The formation of drug excipient adducts was very common based on the sensitive chemical moieties in the drugs and the excipients. The formation of the impurities was not limited to drug related impurities but there were several possibilities of the drug-excipient adduct formations as well as excipient impurities reaction with Active Pharmaceutical Ingredients. Identification of drug degradation in presence of excipients/excipient impurities requires extensive knowledge and adequate analytical characterization data. Systematic literature review and understanding about the drug formulation process, give you a smooth platform in establishing the finished product in the drug market. This paper discusses mechanistic basis of known drug-excipient interactions with case studies and provides an overview of common underlying themes in solid, semisolid and parenteral dosage forms.

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“…Therefore, different degradation pathways such as dehydration, isomerization of double bonds, hydrolysis, rearrangement, and epimerization can be done on it. 17 Rotation of amide bond consequences an equilibrium between trans and cis rotamers of tacrolimus in the pipecolic acid moiety. 18 Pipecolic acid moiety is often considered a vital factor for the biological activities of some natural pharmaceutical products from microbial sources.…”

Section: Introductionmentioning

confidence: 99%

Stability Tests and Analytical Methods of Tacrolimus: A Review

Sajjadi,

Siahi-Shadbad,

Afshar Mogaddam

2022

ImmunoAnalysis

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Tacrolimus is an immunosuppressive drug widely used in organ or tissue transplantation. Furthermore, its anti-inflammatory effects are employed in treatments for psoriasis, uveitis, and vernal keratoconjunctivitis. According to the structural characteristics of tacrolimus, different transformations can be occurred on the drug and produces degradation products. Thus, stability and stress tests have a key role in the quality of tacrolimus with a narrow therapeutic index. Up to now, different studies have been developed for the study of tacrolimus stability under different conditions, and the degradation products were detected by different analytical instruments. Therefore, in the current study, available studies about tacrolimus degradation were collected and categorized into five main parts including acidic hydrolysis, alkaline hydrolysis, thermal, oxidative, and photolytic for better survey. The known degradation products with their chemical structures were also discussed in this study. Moreover, the analytical methods that are applied for drug characterization during stability tests were explained.

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Solid state compatibility study and characterization of a novel degradation product of tacrolimus in formulation

Cited by 12 publications

References 26 publications

Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery

Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery

Drug-Excipient Interactions: Case Studies and Overview of Drug Degradation Pathways

Stability Tests and Analytical Methods of Tacrolimus: A Review

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