ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF ZINC PYRITHIONE IN KETOCONAZOLE SHAMPOO BY RP-HPLC METHOD

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ABOUT AUTHORS:
Sahoo.U1*, Sethy.S.P1, Biswal.S1, Patro.S.K1, Banerjee.M1, Sundeep Kumar.H.K.S1, Patel.D2
*1Department of Pharmaceutical Chemistry
Institute of Pharmacy and Technology, Salipur, Cuttack, Odisha-754202
2ZYG Pharma, Pvt, Ltd, Pithampur, Madhya Pradesh
sarada9439504350@gmail.com

ABSTRACT-
A mobile phase consisting of Acetonitrile and water in the ratio of 60:40 gave a well resolved and sharp peak for Zinc-Pyrithione with a retention time of 11.61 mins. The flow rate was 1 ml/min and effluent was monitored at 322 nm. Zobrax C18 column, run time of 30 min and ambient temperatures were found to be optimum for the analysis. System suitability was performed by injecting five replicate injections of working standard solution. The System suitability results obey all the parameters and found within the acceptable range. The precision study was found to be less than 1 (% RSD). So, it indicates the method is precise. The recovery study was found to be 98 to 102 % and % RSD was found to be less than % 1. So, the method is more accurate, precise, and sensitive.

REFERENCE ID: PHARMATUTOR-ART-1935

INTRODUCTION- Ketoconazole


Fig 1: Structure of Ketoconazole

Chemically ketoconazole is 1-[4-(4-{[(2R, 4S)-2-(2, 4-Dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1, 3-dioxolan-4-yl] methoxy} phenyl) piperazin-1-yl] ethan-1-one

Ketoconazole is a synthetic antifungal drug used to prevent and treat fungal skin infections, especially in immune compromised patients such as those with AIDS or those on chemotherapy. Ketoconazole is sold commercially as an anti-dandruff shampoo, topical cream, and oraltablet. Ketoconazole is very lipophilic, which leads to accumulation in fatty tissues. The less toxic and more effective triazole compounds fluconazole and itraconazole are sometimes preferred for internal use. Ketoconazole is best absorbed at highly acidic levels, so antacids or other causes of decreased stomach acid levels will lower the drug's absorption when taken orally. Absorption can be increased by taking it with an acidic beverage, such as cola.[1] ketoconazole is structurally similar to imidazole, and interferes with the fungal synthesis of ergo sterol, a constituent of fungal cell membranes, as well as certain enzymes. As with all azoles antifungal agents, ketoconazole works principally by inhibiting the enzyme cytochrome P450 14-alpha-demethylase (P45014DM).[2-6]


Fig 2: Structure of Zinc Pyrithione

Chemically ZincPyrithione isbis (2-pyridylthio) zinc 1, 1'-dioxide. Zinc pyrithione is a coordination complex of zinc. This colorless solid is used as an antifungal and antibacterial agent. The pyrithione ligands, which are formally monoamines, are cheated to Zn2+ via oxygen and sulfur centers. In the crystalline state, Zinc pyrithione exists as a centrosymmetric dimmer (see figure), where each zinc is bonded to two sulfur and three oxygen centers.[7]In solution, however, the dimmers dissociate via scission of one Zn-O bond.

Zinc pyrithione is best known for its use in treating dandruff and seborrhea dermatitis [8].It also has antibacterial properties and is effective against many pathogens from the streptococcusand staphylococcusclass. Its other medical applications include treatments of psoriasis, eczema, ringworm, fungus, athletes foot, dry skin, atopic dermatitis, tinea, and vitiligo.

Due to its low solubility in water(8 ppm at neutral pH), zinc pyrithione is suitable for use in outdoor paints and other products that provide protection against mildew and algae. It is an effective algaecide. It is chemically incompatible with paints relying on metal carboxyl ate curing agents. When used in latex paints with water containing high amount of iron, a sequestering agent that will preferentially bind the iron ions is needed. Its decomposition by ultraviolet light is slow, providing years of protection even against direct sunlight.

Zinc pyrithioneproduces its antifungal activity by deriving from of its ability to disrupt membrane transport by blocking the proton pump that energizes the transport mechanism.[9]

From the literature review we identified that, there around 7 to 8 works, related to our paper were done. But our work was little difference from them. First we prepared the shampoo formulation according to the marketing formulation. Then changing some parameters like (mobile phase, column, Temp.) to performed the assay which provided good results in comparison to others. So we choose this method to determined Zinc Pyrithione in Ketoconazole Shampoo Preparation by using Reverse Phase High Performance Liquid Chromatography. [10-18]

METHODOLOGY-

PREPARATION OF KETOCONAZOLE SHAMPOO FORMULATION

Procedure

  • Add 10 gm of Benzyl alcohol, 25 gm of Polysorbate-80, 20 gm of Propylene glycol,10 gm of Ketoconazole,5 gm of Glycol distearate and 75 gm of SLES in to a oily phase kettle and was heated in a (50*c) for 15 minutes.
  • In an aqueous phase container, 1 gm of HPMC was mixed with purified water. Then it was dispersed with (25 gm of SLS+2.5 gm of Poly quaterium+1 gm of EDTA, which were prepared by previously in another container). The pH was adjusted with sodium hydroxide (5.5-6) and was heated in a (50*c) for 20 minutes.
  • In another container add 30 gm of CAPB, 15 gm of dimethicone and 10 gm of Zinc pyrithione. Then it was homonized in a homonizer.Then citric acid was added to adjust the pH (5.5-6).
  • The oil phase content was added with aq.phase content in a compounding kettle, fitted with homonizer & homonized. The content (CAPB, ZnPTO, dimethicone mixture, which were previously prepared) were added to compounding kettle. Then it was mixed and homonized properly and adjusted to the pH 5.5-6.

Determination of λmax of the Zinc Pyrithione by UV spectrophotometer.

Preparation of standard stock solution: Weigh accurately 100mg of Zinc Pyrithione and transferred into a 100 mL volumetric flask containing 30 mL of methanol and then sonicated for 3 minutes and then the volume was made up to the mark with methanol to produce 1mg/mL.

Preparation of working standard stock solution: 10 mL of standard stock solution + 20 ml cupric sulphate solution were transferred into another 100 ml volumetric flask and  left for 1 hour for complex formation then diluted up to the mark with chloroform in order to produce 100 µg/mL.

• 1 ml working standard stock solution was transferred into a 10ml volumetric flask and then the volume was made up to the mark with the methanol to produce 10 µg/mL. It was run in the spectrophotometer to determine the λmax of the Zinc Pyrithione.

Drug-ZPTO.
Solvent- Methanol, Chloroform, & Cupric sulphate solution.
Absorbance Range -0.00A to 1.00A.
Wave length Range- 200nm to 400nm.
Mode- Spectrum. Mode.

• Result: UV spectrum of an analyte comprising two nos λmax (one for lower absorbance & other for higher absorbance)

Table No: 1

Types

λmax

Absorbance

Higher

322nm

0.076

Lower

247nm

0.166

From the above spectrum we concluded that, two spectrums were determined which have two λmax value. One is 322nm (higher wave length) having absorbance 0.070 & other is 247nm (lower wavelength) having absorbance 0.166.

So we choose the λmax 322nm (higher wave length) and setting Absorbance Zero (0), to determined the calibration curve of ZPTO, also setting the instrument in Absorbance mode instead of Spectrum mode. By using serial dilution method, to determined the calibration curve of ZPTO.

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