Analysis and stability study of myristyl nicotinate in dermatological preparations by high-performance liquid chromatography
Department of Pharmacology and Toxicology, The University of Arizona, Tucson, Arizona, United StatesJournal of Pharmaceutical and Biomedical Analysis (Impact Factor: 2.98). 03/2007; 43(3):893-9. DOI: 10.1016/j.jpba.2006.09.007
Myristyl nicotinate is an ester prodrug under development for delivery of nicotinic acid to skin for treatment and prevention of conditions that involve skin barrier impairment such as chronic photodamage and atopic dermatitis or for mitigating skin barrier impairment that results from therapy such as retinoids or steroids. The formulation stability of myristyl nicotinate is crucial because even small amounts of free nicotinic acid cause skin flushing, an effect that is not harmful but would severely limit tolerability. We report here reversed-phase HPLC methods for the rapid analysis of myristyl nicotinate and nicotinic acid in dermatological preparations. Because of the large differences in polarity, myristyl nicotinate and nicotinic acid were analyzed by different chromatographic conditions, but they can be rapidly extracted from cream formulations using HPLC mobile phase as a solvent followed by HPLC analysis in less than 10 min. The methods were validated in terms of linearity, precision and accuracy and mean recovery of myristyl nicotinate from topical creams ranged from 97.0-101.2%. Nicotinic acid at levels of 0.01% in the formulations could be quantified. Stability studies show that myristyl nicotinate formulations are stable at room temperature for 3 years with less than 0.05% conversion to nicotinic acid. These methods will be effective for routine analysis of myristyl nicotinate stability in dermatological formulations.
[Show abstract] [Hide abstract]
- "In compatibility studies, temperature variation is one of the most important parameter to induce rapid chemical and physical alterations in formulations, which is determined by quantification of the active constituents over the time. Unlike a single chemical entity that forms the basis of conventional medicine, traditional Ayurvedic medicine views the polyherbal preparations as they induce combined therapeutic activity.[3–6] This creates a challenge in the development of a stable polyherbal formulation. "
ABSTRACT: Ayurvedic and herbal medicinal products contain a combination of botanicals; each of these contains a number of chemical compounds that may give the anticipated activity in combination. Therefore, it is very important to analyze and evaluate the compatibility of various active constituents and markers from different medicinal plants for their possible chemical interactions with various excipients at different storage conditions during the development of a stable polyherbal formulation. To study chemical stability of kalmegh (Andrographis paniculata) and kutki (Picrorhiza kurroa) extract for their active markers andrographolide, kutkoside and picroside-I and to develop stable polyherbal formulation based on the incompatibility studies. The compatibility study was carried out on individual ethanolic extracts of these two plants along with the commonly used excipients in the ratio of 1:1 at 40 ± 2°C and 75 ± 5% relative humidity and at a refrigeration temperature of 5 ± 1°C for initial, 7-, 15- and 30-day intervals. The analysis was carried out using the validated reverse phase-high-performance liquid chromatography methods. A stable tablet dosage form was developed based on the results of these studies. The study suggested that the active markers of kutki (kutkoside and picroside-I) were found to be degraded in the presence of the kalmegh extract. However, the active marker of the kalmegh extract (andrographolide) was found to be stable. Both the extracts showed excellent compatibility with all the excipients used in making this formulation. No significant decrease in the kutkoside and picroside-I content from the formulation was observed. By separate granulation process the exposure of both the extracts can be minimized thus avoiding the degradation of active markers.
Article: PolyADP-ribosylation and cancer[Show abstract] [Hide abstract]
ABSTRACT: The polyADP-ribosylation reaction results in a unique post-translational modification involved in various cellular processes and conditions, including DNA repair, transcriptional control, genomic stability, cell death and transformation. The existence of 17 members of the poly(ADP-ribose) polymerase (PARP) family has so far been documented, with overlapping functional consequences. PARP-1 is known to be involved in DNA base excision repair and this explains the susceptibility spectrum of PARP-1 knockout animals to genotoxic carcinogens. The fact that centrosome amplification is induced by a non-genotoxic inhibitor of PARP and in PARP-1 knockout mouse cells, is in line with aneuploidy, which is frequent in cancers. Genetically engineered animal models have revealed that PARP-1 and VPARP impact carcinogenesis. Furthermore, accumulating experimental evidence supports the utility of PARP and PARG inhibitors in cancer therapy and several clinical trials are now ongoing. Increasing NAD(+) levels by pharmacological supplementation with niacin has also been found to exert preventive effects against cancer. In the present review, recent research progress on polyADP-ribosylation related to neoplasia is summarized and discussed.
- [Show abstract] [Hide abstract]
ABSTRACT: Octyl nicotinate is an ester prodrug which is under development for delivery of nicotinic acid to skin for treatment and prevention of dermatological conditions that involve skin barrier impairment such as chronic photodamage and atopic dermatitis or for mitigating skin barrier impairment that results from therapy such as retinoids or steroids. We report here an isocratic RF-LC method with water/acetonitrile (10:90, v/v) as a mobile phase, for the rapid analysis of octyl nicotinate in aqueous solutions. The method was validated in terms of linearity, precision, accuracy and mean recovery of octyl nicotinate from skin homogenate ranging from 98.8 to 102.6%. Separation and quantification of amounts as low as 0.25 μg mL−1 octyl nicotinate was accomplished. The kinetic of degradation of octyl nicotinate in aqueous solution at 310, 333, 343, and 353 K was studied. The hydrolysis rate constants for degradation of octyl nicotinate in phosphate buffer and skin homogenate were reported. This method will be effective for routine analysis of octyl nicotinate stability in different formulations in future studies.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.