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

Pharma Admission

Pharma courses

pharma admission

pharma courses

 

{ DOWNLOAD AS PDF }

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

PharmaTutor (ISSN: 2347 - 7881)

Volume 2, Issue 10

Received On: 12/08/2014; Accepted On: 19/08/2014; Published On: 01/10/2014

How to cite this article: AI Bhim, V Jain, R Hasumati; A Review: Determination of Itopride Hydrochloride in biological fluid and Pharmaceutical Dosage Forms; PharmaTutor; 2014; 2(10); 38-44

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

Title

Method

Mobile Phase

Stationary Phase

Wavelength  (nm)

Determination of Itopride Hydrochloride in capsule formulation[7]

HPLC

Methanol-Water-Triehanolamine-Glacial ascetic acid (with the proportion of 40:60:0.5:0.3,v/v/v/v)

C18 column (4.6mm×250mm)

258

Optimized method for the determination of itopride in human plasma[8]


HPLC with flourometric detection

Acetonitrile-Triethylamine-dihydrogen potassium phosphate

(14.5:0.5:85,v/v/v)

octadecylsilica column (55 mm × 4 mm, 3 μm particles),

   250/342 

Chromatographic determination of Itopride Hydrochloride in the presence of its degradation products[9]

HPLC

Methanol-Water(70:30,v/v)

Kromasil column [C18 (5-μm, 25 cm×4.6 mm, ID)]

258

Simultaneous determination of Rabeprazole sodium and Itopride Hydrochloride in solid dosage form[10]

RP-HPLC

Acetonitrile: buffer (35:65 v/v)

Luna C18 (5µ M, 25 cm×4.6 mm i.d) phenomenex

266

Simultaneous determination of Esemoprazole and itopride in capsule[11]

RP-HPLC

Buffer(Ammonium Acetate,pH-5.5):Water:Methanol (25:15:60,v/v/v)

Phenomenex C18 

275

Determination of Itopride Hydrochloride in its pharmaceutical preparation and in bulk drug[12]

HPTLC

Methanol-Ethyl acetate-Toluene-Triethylamine (1.0:2.5:6.0:0.5,v/v/v/v )

Silica gel 60F 254 TLC plates

230

Simultaneous determination of Rabeprazole sodium and Itopride Hydrochloride in solid dosage form[13]

HPTLC

n-butanol:toluene:ammonia (8.5:0.5:1 v/v/v)

precoated silica gel G60F254 plate (10×10 cm)

288

Stability  indicating high performance thin-layer

chromatographic  method for simultaneous estimation of pantoprazole  sodium and itopride hydrochloride

in combined dosage form[14]


HPTLC

Methanol: Water: Ammonium acetate; 4.0:1.0:0.5 (v/v/v)

Aluminium plates  precoated  with  silica gel 60F254 

289

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.

NOW YOU CAN ALSO PUBLISH YOUR ARTICLE ONLINE.

SUBMIT YOUR ARTICLE/PROJECT AT articles@pharmatutor.org

Subscribe to Pharmatutor Alerts by Email

FIND OUT MORE ARTICLES AT OUR DATABASE


 

Pages

FIND MORE ARTICLES