A Review on Various Analytical Methodologies of Naproxen

Nisha Sahu, Sukrita Shriwas, Yeendeswari Gendre, Aakanksha Sinha, S.J. Daharwal

University institute of pharmacy, Pt. Ravishanker Shukla University, Great Eastern Road, Amanaka, Raipur, Chhattisgarh, India.

ABSTRACT:

Naproxen is a Nonsteroidal Anti-Inflammatory Drug (NSAID). It is mostly used to treat pain or inflammation caused by conditions such as arthritis, gout, tendinitis or menstrual cramps. Naproxen is available in isolated dose with various similar anti-inflammatory drugs, i.e.; esomeprazole, pantoprazole, paracetamol, ranitidine, sumatriptan and ibuprofen. This survey evaluates various methods for the analysis of Naproxen in bulk drugs and formulated products. Analytical procedures are critical for determining compositions, they allow as to obtain both qualitative and quantitative results utilizing by the advanced analytical tools. This include HPLC, HPTLC, UV- spectrophotometry, capillary electrophoresis, and electrochemical methods. The UV-spectrophotometry method is applied for the investigation of Naproxen in biological media, bulk samples and in various dosage formulations. The HPLC technique of Naproxen alone and the combination, including parameters such as matrix, stationary phase, mobile phase, wavelength detection, etc. HPTLC method parameters such as stationary phase, mobile combination phase, RF value, etc. To maintain high commercial product quality standards and to adhere to regulatory requirements, analytical technique development is necessary. Drug concentrations are measured using bioanalytical techniques. Development and validation of bioanalytical method is important to understand the pharmacokinetics of any drug and/or its metabolites.

KEYWORD:  Naproxen, Analytical methods.

1. Introduction

Naproxen was first introduced to the prescription drug market in 1976 under the name Naprosyn. In 1976, its salt counterpart, naproxen sodium, was released for prescription use only under the name Anaprox in June 1980 (Chander et al., 2011). Naproxen is a structurally (2S)-2-(6-methoxynaphthalen-2-yl) propanoic acid nonsteroidal anti-inflammatory drug that exhibits both antipyretic and analgesic behavior  (Elsinghorst et al., 2011). Naproxen is derived from propionic acid. The mechanism of action of naproxen, as with other NSAIDs, is believed to be associated with inhibition of cyclooxygenase activity. Two main unique cyclooxygenases are described in mammals. A constitutive cyclooxygenase, COX-1, synthesizes a prostaglandin essential for normal gastrointestinal and renal function. Inducible cyclooxygenase, COX-2, produces a prostaglandin involved in inflammation. COX-1 inhibition is thought to be associated with gastrointestinal and renal toxicity, while COX-2 inhibition provides anti-inflammatory activity.

1.1   Physiochemical Properties

A colorless, odorless, tasteless, crystalline solid with the chemical formula C₁₄H₁₄O₃. Naproxen is insoluble in cold water and their melting point 152⁰C. Molecular weight of Naproxen 230.26 g/mol (Wongrakpanich et al., 2018).

                                                                                          Fig 1:
 Structure of Naproxen

1.2   Pharmacokinetic properties

Naproxen achieves optimal plasma concentration within 2-4 hours as a standard when applying a technologically optimal approach for naproxen in the form of a sodium salt. Naproxen sodium salt achieves maximal plasma levels within 1-2 hours that combined with the quick action onset up to 15 min for quick and effective analgesic effect. Naproxen has a volume of distribution of 0.16 L/kg. Naproxen is heavily metabolized in the liver and undergoes both phase I and phase II metabolism. After oral administration, about 95% of naproxen and its metabolites can be recovered in the urine with 66-92%. and less than 5% of naproxen is excreted in the feces. The elimination half-life of naproxen is reported to be 12-17 hours. Naproxen is highly protein bound with >99% of the drug bound to albumin at therapeutic levels  (Elsinghorst et al., 2011 , Davies et  al., 1997).

1.3   Pharmacodynamic properties

Naproxen is an established non-selective NSAID and useful as an analgesic, anti-inflammatory and antipyretic. Similar to other NSAIDs. The pharmacological activity of naproxen can be attributed to the inhibition of cyclo-oxygenase. Which is turn reduces prostaglandin synthesis in various tissues and fluids including the synovial fluid, gastric mucosa, and the blood ^[5]. Although naproxen is an effective analgesic, it can have unintended effects in the patient. Naproxen can adversely affect blood pressure although the increase was not as significant as that found with ibuprofen use ^[6]. Studies have found that the risk of upper gastrointestinal (GI) bleeding include use of corticosteroids or anticoagulants, and a history of gastrointestinal ulcers (Elsinghorst et al., 2011 , Mellemkjær et al., 2002).  

1.4   Approved dosage forms of Naproxen

The available medicines in the market along with the brand name and manufacturer are presented in Table 1 and 2.

Table 1: Naproxen dosage forms along with brand names ^[8]

Table 2: Naproxen dosage forms in combination ^[8]

2. Need of Analytical and Bioanalytical method

The result of developing analytical techniques are official test procedures. As a result of this, quality control laboratories employed these methods to evaluate the effectiveness, purity, safety, and performance of drug products. Regulatory organizations place a high priority on production-related analytical methods. For the treatment to be approved by regulatory authorities, the applicant must demonstrate control over the entire drug development process using recognized analytical methods (Chauhan et al., 2015). Stability testing (Q1), validation of analytical techniques (Q2), impurities in drug substances and products (Q3), and specifications for new drug substances and products (Q6) are analytical guideline documents that the ICH issued. Bioanalytical methods aim of this method is to quantify a drug and metabolite of drug or its biomarkers concentration in biological fluids example, blood, plasma, serum, urine and saliva as well as tissue extracts. It is essential for the development of accurate and very efficient methods for performing both qualitative and quantitative analysis, as well as cost-effective methodologies and shorter analysis time. Naproxen extraction percent retrieval trial since human Plasma ware discovered to be 91 and 98.9%. The LOD and LOQ were discovered to be 0.03% and 0.10mg/ml, respectively ( Elsinghorst et al., 2011 ,Prajapati et al., 2022) .

3. Analytical Method Development by UV Spectrophotometer

UV spectroscopy is the absorption or reflection spectroscopy of the ultraviolet and adjacent visible region of the electromagnetic spectrum. It is also known as UV visible spectrophotometry. The UV Spectroscopy follow the Beer’s and Lambert’s law, and detected by UV spectrophotometer. The range of electromagnetic radiation (EMR) spectrum in UV spectroscopy is 200-800nm. UV spectrometry method has major advantages like, analyze the chemical properties, concentrations, and identify unknown materials of samples. The only requirement is that the sample absorb in the UV visible range, indicating that it is a chromophore. Absorption spectroscopy a side from the wavelength, the parameters of interest are absorbance, transmittance (%T), and reflectance (%R), as well as their variation over time (Stuckey et al., 1952). Some of the examples are mentioned in Table 3.

Table 3: Analytical method development using UV spectrophotometer

4. Analytical method development by HPLC

High-performance Liquid Chromatography (HPLC) is now one of the most powerful tools in analytical chemistry. It has the ability to separate, identify, and quantify the compound that are present in any sample that can be dissolved in a liquid. High performance liquid chromatography is widely used for quantitative as well as qualitative analysis of drug products (Chawla et al., 2019). The principal is that a solution of the sample is injected in to a column of a porous material (stationary phase) and a liquid (mobile phase) is pumped at high pressure through the column. The separation of sample is based on the difference in the rates of migration through the column arising from different partition behavior of different components, elution at different times takes place (Rajan et al., 2015). The HPLC is more versatile than gas chromatography it is not limited to volatile and thermally stable sample and the choice of mobile phase and stationary phase is wider range available. HPLC has numerous advantages like- Simultaneous analysis, high resolution, high sensitivity, good repeatability, small sample size, moderate analysis condition, easy to fractionate the sample and purifying also (Vidushi et al., 2017). A HPLC is frequently utilized by researchers to develop the method. Examples of some those are mentioned in Table 4.

Table 4: Analytical method development using HPLC method

5. Analytical Method Development Using HPTLC Method

High Performance Thin Layer Chromatography (HPTLC) is a sophisticated and automated from of the thin layer chromatography (TLC) with better and advance separation efficiency and detection limits It is also known as High Pressure Thin Layer Chromatography/ planar chromatography or flat- bed chromatography. It is a powerful analytical method equally suitable for quantitative and qualitative analytical task. Separation may result due to adsorption or partition or by both, phenomenon depending upon the nature of adsorbents used on plates and solvents systems used for development. Different aspects on HPTLC fundamental, Principle, theory, undertaken, instrumentation, implementation, optimization, validation, automation and qualitative and quantitative analysis, application, phytochemical analysis, biochemical analysis, herbal drug qualification, analytical analysis, fingers print analysis and potential for hyphenation (HPTLC-MS, HPTLCFTIR and HPTLC Scanning Diode Laser) have been reported (Ramu et al., 2018). Examples of a few of those are given in Table 5.

Table 5: Analytical method development using HPTLC method

6. Bioanalytical Method Development

The evaluation of bioavailability, bioequivalence, and pharmacokinetics research makes extensive use of bioanalytical methods for the quantitative study of medicines and their metabolites in biological matrix or media such as saliva, urine, plasma, serum, etc. The process of developing a procedure that enables the identification and measurement of drugs and their metabolites in biological matrix or medium is known as "bioanalytical method development." A compound can frequently be measured using a variety of techniques, and selecting the best one requires taking into account a number of factors, including the chemical characteristics of the analyte, concentration levels, sample matrix, cost of the analysis, speed of the analysis, quantitative or qualitative measurement, precision needed, and necessary equipment. For the process of method development and validation, an appropriate protocol should be created. Sample preparation, chromatographic separation, and detection using the appropriate analytical method are the three integral, linked components of method development. Effective execution of bioequivalence, pharmacokinetic, and toxicokinetic studies depends greatly on the use of bioanalytical methods for quantitative determination of drugs and their metabolites (Charde et al., 2013). In pharmaceutical research companies the development of comprehensive bioanalytical methods is very important during the process of drug discovery and development ( Moein et al., 2017).

Table 6:  Bioanalytical method development using various methods

7. Conclusion

In this review, the various analytical and bioanalytical techniques utilized for the estimation of naproxen as well as in the bulk form of the medications have received the most attention. Combinations of naproxen are present in various dosage formulations. The development of analytical techniques such as UV spectrophotometry, HPLC, HPTLC, RP-HPLC, TLC, and other techniques has been the focus of research. All of the established analytical techniques have increased levels of automation and processing of samples are very sensitive, reliable, reproducible, and precise. A literature review is conducted for collecting data on various analytical and instrumental analytical techniques. A unique analytical approach could be developed using such data.

8. Competing Interests

Authors reports no conflict of interest concerning this review article.

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