UV Spectroscopy Analysis for Itraconazole

Taranjeet Kukreja¹, Swarnlata Saraf ^*

¹University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur - 492010, Chhattisgarh, India

Abstract:

Itraconazole is a triazole antifungal agent that is synthesised. Itraconazole has been manufactured into a variety of pharmacological formulations and administered in a variety of ways. Itraconazole pills are used to treat pulmonary fungi that can cause fungal infection and spread throughout the body. Because Itraconazole is not yet officially listed in any pharmacopoeia, only a few procedures for quality control and stability testing in pharmaceutical formulations have been published. The goal of this study is to develop a more precise, easy, and cost-effective spectrophotometric approach for analysing Itraconazole in bulk and capsule dosage forms with improved precision, accuracy, and sensitivity. The UV spectroscopic determination was performed with Chloroform as the solvent at an absorption maximum of 267 nm. Linearity over the concentration range in the UV spectroscopic approach. The linearity of Itraconazole over the concentration range was found to be 1-10 g/ml using the UV spectroscopic technique, with a correlation coefficient of 0.999. The findings of the analyses were statistically and the recovery studies have confirmed this.

Keywords: Itraconazole, pharmacopoeia, UV spectroscopic technique, Quality control.

Introduction

Itraconazole is a triazole antifungal agent that is synthesised. Itraconazole is a racemic combination of four diastereomers (two enantiomeric pairs), each with three chiral centres, in a ratio of 1:1:1:1. The following nomenclature can be used to denote it: 4-[4-[4-[4-[[ 2. (2, 4-dichlorophenyl) - two (1H-1, 2, 4- triazole- 1-ylmethyl) - 1,3- dioxolan-4-yl] methoxy]phenyl] piperazine-1- yl]phenyl] piperazine-1- yl]phenyl] piperazine-1- yl]phenyl] piperazine-1- yl]phenyl] piperazine-1- -2-(1-methyl propyl) -2, 4-dihydro-1, 2-dihydro-1, 2-dihydro-1, 2-dihydro-1, 2-dihydro-1, 2-dihydro (Fig 1).

Figure1: Itraconazole's structure

C35H38Cl2N8O4 is the molecular formula and the chemical molecular weight is noted to be705.64. [1-4] It's a powder that's white to slightly yellowish. In alcohols, it is very partially soluble, but in dichloromethane, it is completely soluble. Itraconazole is an extremely lipophilic compound that is water insoluble. It's a very weak base (pKa =3.7) that only ionises at very low pH levels. It's a three-chiral hydrophobic antimycotic medication that's employed in clinical trials as a stereoisomeric combination. [5] It is an oral triazole antifungal medication efficacious against dermatophytes, species of bacteria, Malassezia, and penicillium species having a broad range of activity and Histoplasma capsulatum var. capsulatum, among other fungal species. [6,7]

Mechanism of action of Itraconazole

It binds to 14-demethylase, a cytochrome P-450 enzyme that is required for the conversion of lanosterol to ergosterol. Because ergosterol is a necessary component of the fungal cell membrane, inhibiting its synthesis increases cellular permeability, causing cellular contents to flow out. Itraconazole can also decrease endogenous respiration, interact with membrane phospholipids, prevent yeasts from transforming into mycelial forms, block purine uptake, and disrupt triglyceride and/or phospholipid production. When itraconazole is taken with food, its oral bioavailability increases and plasma concentrations are nearly twice as high as when taken when fasting. Itraconazole is metabolised primarily in the liver by the cytochrome p450 3a4 isoenzyme system, which produces various metabolites, the most significant of which is hydroxyl itraconazole 8. [9] It is metabolised in the liver, primarily through an oxidative pathway, forming the bioactive metabolite hydroxyl itraconazole. [10]

Materials and methods

Experimental

Chemicals and reagents: Throughout UV spectrophotometric technique, development and validation Chloroform was used.

Instrumentation

UV spectrophotometric technique was performed on a double beam UV-visible spectrophotometer (Shimadzu, model 1800) having two matched quartz cells with a 1 cm light path.

Selection of solvent

For the analysis of Itraconazole, Chloroform had been selected as the ideal solvent for spectrophotometry.

Standard stock solutions preparation

A 10 mg Itraconazole reference standard was accurately weighed and transferred to a 10 ml volumetric flask, where it was dissolved and diluted up to the mark using chloroform to yield a stock solution with a strength of 500g/ml. Diluting 1 ml of stock solution to 5 ml with chloroform yielded a 50 g/ml working standard solution.

Preparation of Sample stock solution

For analysis of the drug, 10mg of the drug itraconazole was weighed and transferred to a 10ml volumetric flask and dissolved with chloroform. The itraconazole drug solution was diluted to get a final concentration of 10μg/ml. The absorbance of these solutions was measured at 267 nm. The amount of Itraconazole was calculated using the calibration curve.

Formula:

 %Purity=Sample absorbance / Standard absorbance X 100

1.     Method validation

The method was validated according to the International Conference on Harmonization (ICH)

Q2B guidelines 1996 for validation of analytical procedure to determine the linearity,

limit of detection, accuracy and precision.

2.     Linearity & Range

Under the experimental conditions, the calibration graphs of the absorbance versus

Concentration was found to be linear over the range of 0.2-1.0μg/ml for the proposed method.

The statistical analysis of data obtained for estimation of Itraconazole is indicated chloroform

of accuracy for the proposed methods evidenced by the low values of standard deviation and

coefficient of variation. The results are noted below:

Table 1: Itraconazole Linearity Data

Results and Discussion

The purpose of this study was to validate an Itraconazole using a UV-Spectrophotometric technique under optimal conditions. The validation parameters' results were found to be within acceptable limits. Within the concentration range of 1-10g/ml, itraconazole followed linearity. The measured linearity range suited Beer-law Lambert's well, and the corresponding regression coefficient (r=0.999) indicates a high degree of technique sensitivity, as shown in Table 1. The number of drugs detected and the findings of the analysis demonstrate that the percentage of the drugs found and the number of drugs found was in good accord.

Conclusion

UV-Spectrophotometer techniques produced equivalent results. The linearity of Itraconazole over the concentration range was found to be 1-10 g/ml using the UV spectroscopic technique, with a correlation coefficient of 0.999. The findings of the analyses were statistically and the recovery studies have been confirmed.

Acknowledgment

I am thankful to the University Institute of Pharmacy (UIOP), Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India for my practical support. I also want to thank Prof. Swarnlata Saraf, University Institute of Pharmacy (UIOP), Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India for her valuable suggestions and guidance.

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