- Novel spectral manipulations for determinations of Tolnaftate along with related toxic compounds: Drug profiling and a comparative study. [Journal Article]
- SASpectrochim Acta A Mol Biomol Spectrosc 2019 Jun 19; 223:117290
- A comparative study using novel quadruple divisor and mean centering of ratio spectra spectrophotometric methods was developed for resolution of five- component mixture of Tolnaftate, β-naphthol (Tol…
A comparative study using novel quadruple divisor and mean centering of ratio spectra spectrophotometric methods was developed for resolution of five- component mixture of Tolnaftate, β-naphthol (Tolnaftate alkaline degradation product and its toxic impurity), methyl(m-tolyl)carbamic acid (Tolnaftate alkaline degradation product), N-methyl-m-toluidine (Tolnaftate toxic impurity) and methyl paraben (as a preservative). For the novel quadruple divisor method, each component in the quinary mixture was determined by dividing the quinary mixture spectrum by a sum of standard spectrum of equal concentration of the other four components as a quadruple divisor. First derivative of each ratio spectra was then obtained which allowed selective determination of each component without interference from other components in the mixture. The second method was mean centering of ratio spectra that depended on utilizing the mean centered ratio spectra in four successive steps leading to enhancement of the signal to noise ratio. The absorption spectra of the five studied components were recorded in the wavelength range of 210-350 nm. The mean centered fourth ratio spectra amplitudes for each component were used for its determination. The developed methods were successfully applied for determination of laboratory prepared quinary mixtures to ensure method's specificity, then, were further applied on Tinea Cure® cream where no interference from excipients. For the first time, Tolnaftate was determined along with its toxic impurity; β-naphthol, that could be absorbed by the skin, causing systemic toxic effects, unlike Tolnaftate that poorly absorbed, indicating the significance of this work. The proposed methods were statistically compared with each other and with the reference method. Furthermore, ICH guidelines were followed for their validation.
- Two validated chromatographic determinations of an antifungal drug, its toxic impurities and degradation product: A comparative study. [Journal Article]
- BCBiomed Chromatogr 2019; 33(8):e4547
- Tolnaftate, a thionoester anti-fungal drug, was subjected to alkaline hydrolysis to produce methyl(m-tolyl)carbamic acid and β-naphthol (tolnaftate impurity A). N-Methyl-m-toluidine, tolnaftate impur…
Tolnaftate, a thionoester anti-fungal drug, was subjected to alkaline hydrolysis to produce methyl(m-tolyl)carbamic acid and β-naphthol (tolnaftate impurity A). N-Methyl-m-toluidine, tolnaftate impurity D, was synthesized and structurally elucidated along with tolnaftate alkaline degradation products using IR, H1 NMR and MS. Two stability-indicating HPTLC and RP-HPLC methods were developed and validated, for the first time, for determination of tolnaftate, its alkaline degradation products and toxic impurities in the presence of methyl paraben, as a preservative in Tinea Cure® cream. The proposed HPTLC method depended on separation of the studied components on TLC silica gel F254 plates using hexane-glacial acetic acid (8:2, v/v) as a developing system and scanning wavelength of 230 nm. The proposed RP-HPLC method was based on separation of the five components on an Eclipse plus C18 column. The mobile phase used was acetonitrile-water containing 1% ammonium formate (40:60, v/v), with a flow rate of 1 mL/min and detection wavelength of 230 nm. The proposed methods allowed the assay of tolnaftate toxic impurities, β-naphthol and N-methyl-m-toluidine, down to 2%, allowing tracing of β-naphthol that could be absorbed by the skin causing systemic toxic effects, unlike tolnaftate, indicating the high significance of such determination. International Conference on Harmonization guidelines were followed for validation.
- Efficacy of topical clotrimazole vs. topical tolnaftate in the treatment of otomycosis. A randomized controlled clinical trial. [Journal Article]
- BJBraz J Otorhinolaryngol 2019 Feb 18
- CONCLUSIONS: Clotrimazole cream treatment is more effective than Tolnaftate for uncomplicated otomycosis. More studies are needed to corroborate our results.
- The solid-state conformation of the topical antifungal agent O-naphthalen-2-yl N-methyl-N-(3-methylphenyl)carbamothioate. [Journal Article]
- ACActa Crystallogr C Struct Chem 2018 11 01; 74(Pt 11):1495-1501
- Tolnaftate, a classic antifungal compound, has been found to crystallize from 1:1 (v/v) acetone-water as large flat colorless needles in the centrosymmetric monoclinic space group P21/c. These crysta…
Tolnaftate, a classic antifungal compound, has been found to crystallize from 1:1 (v/v) acetone-water as large flat colorless needles in the centrosymmetric monoclinic space group P21/c. These crystals contain a 50:50 mixture of the (+ap,-sp,+ac,-ac) and (-ap,+sp,-ac,+ac) conformers. The bond lengths in the central CNOS unit are 1.3444 (19), 1.3556 (18) and 1.6567 (15) Å for C-N, C-O and C-S, respectively, and the CNOS and C3N moieties are flat and nearly coplanar with each other, consistent with the C-N bond possessing partial double-bond character. Tolnaftate and the four most closely related N,N-disubstituted thiocarbamates in the Cambridge Structural Database (CSD) all exist as E-conformational isomers in the solid state. Among these five compounds, tolnaftate is the only one in which the N-tolyl moiety is positioned trans to the S atom, i.e. the N-aryl substituent in each of the other compounds is positioned cis to their respective S atom. Notably, and more importantly, our experimental X-ray structure is unlike all prior theoretical models available for tolnaftate. The implication, either directly or indirectly, is that some of those theoretical models used in earlier studies to explain the spectroscopic properties of tolnaftate and to suggest which protein-ligand interactions are responsible for the binding of tolnaftate to squalene epoxidase are either inappropriate or structurally unreasonable, i.e. the results and conclusions from those prior studies are in need of critical reassessment.
- Naphthalene, a versatile platform in medicinal chemistry: Sky-high perspective. [Review]
- EJEur J Med Chem 2019 Jan 01; 161:252-276
- Naphthalene, a cytotoxic moiety, is an extensively explored aromatic conjugated system with applications in various pathophysiological conditions viz. anticancer, antimicrobial, anti-inflammatory, an…
Naphthalene, a cytotoxic moiety, is an extensively explored aromatic conjugated system with applications in various pathophysiological conditions viz. anticancer, antimicrobial, anti-inflammatory, antiviral, antitubercular, antihypertensive, antidiabetic, anti-neurodegenerative, antipsychotic, anticonvulsant, antidepressant. Naphthalene epoxides and naphthoquinones are most reactive metabolites of naphthalene and are responsible for the covalent interaction with cysteine amino acid of cellular proteins for cytotoxic nature. Many naphthalene derived bioactive phytoconstituents are present in nature including podophyllotoxins (Etoposide, teniposide), bis-ANS 82, Rifampicin, Justiprocumin A, B, Patentiflorin A. The naphthalene-based molecules, viz. Naphyrone, tolnaftate, naftifine, nafcillin, terbinafine, propranolol, nabumetone, nafimidone, naproxen, duloxetine, lasofoxifene, bedaquiline etc. have also been approved by FDA and are being marketed as therapeutics. Thus, the naphthalene scaffold emerges as an important building block in drug discovery owing to its broad spectrum of biological activities through varying structural modifications. This review incorporates the pharmacological aspects of different types of chemically modified naphthalene-based molecules along with their activity profile. This compiled information may serve as a benchmark for the alteration of existing ligands to design novel potent molecules with lesser side effects.
- Healthcare Priority-Setting: Chat-Ting Is Not Enough Comment on "Swiss-CHAT: Citizens Discuss Priorities for Swiss Health Insurance Coverage". [Comment]
- IJInt J Health Policy Manag 2018 07 28; 7(10):961-963
- CHAT has its limits. It is a three-hour exercise. However, the real world problems of healthcare rationing and priority-setting are too complex for a three-hour exercise. What is needed, as a supplem…
CHAT has its limits. It is a three-hour exercise. However, the real world problems of healthcare rationing and priority-setting are too complex for a three-hour exercise. What is needed, as a supplement, are sustained processes of rational democratic deliberation that can address the challenges to healthcare justice posed by costly emerging medical technologies, such as these targeted cancer therapies.
- Drugs and Lactation Database (LactMed): Tolnaftate [BOOK]
- BOOKNational Library of Medicine (US): Bethesda (MD)
- Topical tolnaftate has not been studied during breastfeeding and no data are available on the extent of its absorption after topical application. Because it is probably poorly absorbed after topical …
Topical tolnaftate has not been studied during breastfeeding and no data are available on the extent of its absorption after topical application. Because it is probably poorly absorbed after topical application, it is considered a low risk to the nursing infant. Avoid application to the nipple area and ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. Only water-miscible cream, gel or liquid products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking.
- We're Stressed Out: BET-Ting on Oxidative Stress? [Comment]
- BBioessays 2018; 40(5):e1800049
- FRET-ting about RhoA signalling in heart and vasculature: a new tool in our cardiovascular toolbox. [Comment]
- CRCardiovasc Res 2018 04 01; 114(5):e25-e27
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- Enhancement of the topical tolnaftate delivery for the treatment of tinea pedis via provesicular gel systems. [Journal Article]
- JLJ Liposome Res 2017; 27(4):324-334
- Tolnaftate is a thiocarbamate antifungal drug which is therapeutically active against dermatophytes that cause various forms of tinea. Due to the small amount of tolnaftate released from ordinary oin…
Tolnaftate is a thiocarbamate antifungal drug which is therapeutically active against dermatophytes that cause various forms of tinea. Due to the small amount of tolnaftate released from ordinary ointment bases and insufficient penetration through the infected skin layers the need to incorporate the drug in a more suitable pharmaceutical form has evolved. A provesicular system is one such form that can solve these problems. Once in contact with the skin, dilution with moisture occurs and the provesicular system rapidly transforms into a vesicular one. Provesicular systems were prepared according to full-factorial experimental design. Plain provesicular systems were compared with systems containing Phospholipon 80 H and Lipoid S45 as penetration enhancers. Design expert software was used to analyze the effect of formulation variables (type of Span used as well as the presence or the absence of the penetration enhancer and its type) on the dependent variables: percent encapsulation efficiency (EE%), vesicle size and percent in vitro drug released). Three formulations were chosen; a plain provesicular system (PV-2), one containing Phospholipon 80H (PV-6) and another containing Lipoid S45 (PV-10) with the goal to reveal the effect of penetration enhancer on morphology, rheological properties and ex vivo permeation using confocal laser scanning microscopy (CLSM). Analysis of CLSM results showed that the penetration enhancing effect for the tested formulations followed the order PV-10 > PV-6 > PV-2. Promising clinically active treatment for tinea patients could be expected as shown by the in vivo permeation results for the provesicular systems as suggested by the CLSM results.