A REVIEW: DETERMINATION OF ITOPRIDE HYDROCHLORIDE IN BIOLOGICAL FLUID AND PHARMACEUTICAL DOSAGE FORMS

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ABOUT AUTHORS:
Asif I Bhim*, Vineet Jain, Hasumati Raj
Shree Dhanvantary Pharmacy College,
Kim, Gujarat, India
bhimiqbal23@gmail.com

ABSTRACT:
Itopride Hydrochloride is a novel, synthesized, gastro prokinetic drug, which stimulates gastrointestinal motor activity through the synergistic effects of dopamine D2-receptor blockade and acetylcholine esterase inhibitors. Chemically, it is N-[[4-[2-(Dimethyl amino) ethoxy] phenyl] methyl]-3, 4-dimethoxy benzamide hydrochloride. Benzamide structure, amide and ether linkages in the drug molecule make it susceptible to degradation. Thus a prokinetic drug like Itopride Hydrochloride by virtue of its efficacy and tolerability could be considered as a drug of first choice and a welcome addition to the drug armamentarium for the symptomatic treatment of NUD (non-ulcer Dyspepsia) and other gastric motility disorders including functional bowel disorders. This review consists of various analytical methods for determination of Itopride Hydrochloride in various marketed pharmaceutical preparation and in biological fluids. Analytical method consists of various spectroscopic methods, chromatographic methods and other methods.

REFERENCE ID: PHARMATUTOR-ART-2261

INTRODUCTION:^[1-6]

STRUCTURAL FORMULA: ^[4]

MOLECULAR FORMULA: C₂₀H₂₆N₂O₄HCL

MOLECULAR WEIGHT: 394.93 g/mol

CHEMICAL NAME:
N-[[4-[2-(Dimethyl amino) ethoxy] phenyl] methyl]-3, 4-dimethoxy benzamide hydrochloride.

CATEGORY: Anticholinesterase

DOSE: 150 mg daily

DESCRIPTION: white amorphous powder

SOLUBILITY:
Soluble in methanol, water, dimethyl sulphoxide, N, N-dimethyl formemide. Springily soluble in ethanol, propylene glycol, polyethylene glycol. Very slightly soluble in hexane, dichloromethane, methyl benzene.

PHARMACOLOGICAL ACTION:
Itopride has anticholinesterase (AchE) activity as well as dopamine D2 receptor antagonistic activity and is being used for the symptomatic treatment of various gastrointestinal motility disorders. It is well established that M3 receptors exist on the smooth muscle layer throughout the gut and acetylcholine (ACh) released from enteric nerve endings stimulates the contraction of smooth muscle through M3 receptors. The enzyme AChE hydrolyses the released ACh, inactivates it and thus inhibits the gastric motility leading to various digestive disorders. Besides ACh, dopamine is present in significant amounts in the gastrointestinal tract and has several inhibitory effects on gastrointestinal motility, including reduction of lower esophageal sphincter and intragastric pressure. These effects appear to result from suppression of ACh release from the myenteric motor neurons and are mediated by the D2 subtype of dopamine receptors. Itopride, by virtue of its dopamine D2 receptor antagonism, removes the inhibitory effects on Ach release. It also inhibits the enzyme AchE which prevents the degradation of Ach.
The net effect is an increase in ACh concentration, which in turn, promotes gastric motility, increases the lower esophageal sphincter pressure, accelerates gastric emptying and improves gastro-duodenal coordination (Figure)
This dual mode of action of Itopride is unique and different from the actions of other prokinetic agents available in the market.

Figure: Mode of action of Itopride. ^[4]

PHARMACOKINETICS:
On oral administration, Itopride is rapidly and extensively absorbed and peak serum concentrations are achieved within 35 minutes after oral dosing.  Thus it has a rapid onset of action, unlike cisapride and mosapride, which take around 60 minutes to reach peak plasma concentrations. Itopride is metabolized in the liver by N-oxidation to inactive metabolites by the enzyme flavin-containing monooxygenase (FMO).The half-life of Itopride is about 6 hours. It is excreted mainly by the kidneys as metabolites and unchanged drug

SIDE EFFECTS:
Rash, diarrhea, giddiness, exhaustion, back and chest pain, increased salivation, constipation, abdominal pain, headache, sleeping disorder, dizziness, galactorrhea and gynecomastia.

ANALYTICAL METHODS:
This all are the methods which are used for the determination of Itopride Hydrochloride in marketed formulation and in biological fluids. This all analytical methods are reported which are seen during the literature survey. This article describes the review on the all reported analytical methods with specific conditions.

I.  COMPENDIAL METHODS:
Itopride Hydrochloride is not official in any pharmacopeia.

II. CHROMATOGRAPHIC METHODS: ^[7-14]
Various chromatographic methods are used for the determination of the Itopride Hydrochloride alone or combination with other drugs in various marketed formulation and in biological fluids like human plasma and urine. Chromatographic methods like High performance liquid chromatography (HPLC/RP-HPLC), High performance thin layer chromatography (HPTLC) with UV detection or with flourometric detection are used. In which the stationary phase commonly used is C18 column and commonly used wavelength for detection is 258nm.Mobile phase is varies with condition of method in various proportion. Below in table describes the summary of the various chromatographic methods are used with the method description.

Table No.1: Summary of Chromatographic Methods of Itopride  hydrochloride

II.UV SPECTROSCOPIC METHOD: ^[15-19]
A simple, precise and economical spectrophotometric method for the estimation of Itopride Hydrochloride in pharmaceutical bulk and tablet dosage form was developed and validated. Identification was carried out using a UV- visible double beam spectrophotometer detector with working wavelength at 258nm in water and methanol medium. The method was validated with respect to its specificity, linearity range, accuracy and precision in analytical media. Itopride Hydrochloride show the maximum absorbance (λmax) at 258 nm. Simple UV spectroscopy, first derivative spectroscopy, AUC method and absorption ratio methods are reported for determination of the Itopride Hydrochloride in marketed formulation. Below in table describes the various chromatographic methods with the method description and condition which are reported on review literature.

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Table No.2: Summary of UV spectroscopic methods of Itopride Hydrochloride

III.MISCELLANOUS METHODS: ^[18-21]
Most widely used methods are mainly HPLC, UV and HPTLC for determination of Itopride Hydrochloride in various formulation or in biological fluids but along with that other methods are also used which are seen during the literature survey. The summary of that methods are described below in table.

Table No.3: Summary of Miscellaneous methods of Itopride    Hydrochloride

CONCLUSION:
The presented review highlights on various analytical methods reported on Itopride Hydrochloride and in combination with other drug. HPLC-HPTLC-UV methods were found to be most widely used. Various chromatographic conditions are presented in under Table. The faster time, high sensitivity; specificity and better separation efficiency enable HPLC to be used frequently for the determination of Itopride Hydrochloride in the comparison with the other methods. There is no doubt on the fact that these chromatographic methods are rapid and far more economical. Other methods are also useful. In this way various analytical methods for the estimation of Itopride Hydrochloride in bulk or in various matrixes like plasma, alone or in combination with other drugs is discussed. The presented information is useful for the researchers especially those involved in the formulation development and quality control of Itopride Hydrochloride in combination with other drug.

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