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  • A Concise Review on Analytical Profile of Dipyridamole as Coronary Vasodilator

  • Department of Pharmaceutical Quality Assurance, Shri Sai College of Pharmacy Khandala, Tal. Vaijapur, Dist. Chh. Sambhajinagar 431116

Abstract

Dipyridamole is a classic platelet inhibitor which has been a key medicine in clinical therapy of thrombosis and cerebrovascular disease and it act as a coronary vasodilator used as an alternative to exercise in thallium myocardial perfusion imaging for the evaluation of coronary artery disease in patients who cannot exercise adequately results to stroke. Drug is of crucial importance to treatment and related research all over the world, so it is great interest of study to overview the analytical profile of Dipyridamole and in combination. The significant work is already reported for estimation of Dipyridamole. The concise review consists comparison and discussion of about over the 30 methods of analyzing the Dipyridamole. The privilege applicability of Dipyridamole was found by various HPLC method and subsequently UV method. Very few literatures were reported by UPLC and HPTLC methods. The Dipyridamole found in combination with Dipyridamole and Aspirin which are mostly used. The present article attempts to review many existing methodologies and the instrumental conditions that were applied in the last decade to quantify Dipyridamole and its metabolites. The authors have made special efforts to gather and compile the brand names of Dipyridamole alone and in combination. Such knowledge will assist in the development of new analytical methodologies in pharmaceutical research. The investigation will be useful and beneficial pre-formulation research and further analytical study of Dipyridamole.

Keywords

Dipyridamole, HPLC, HPTLC, LC-MS/MS, UV-Spectrophotometry

Introduction

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Dipyridamole is a prescription that represses blood cluster development when given constantly and causes vein expansion when given at high portions over a brief timeframe. Artificially dipyridamole (DPM) is 2, 2, 2, 2 - (4, 8-di (piperidin-1-yl) pyridimo [5,4d] pyrimidine-2, 6-diyl) bis (azanetriyl) tetra ethanol. Dipyridamole it is an unscented yellow crystalline powder, having a severe taste, it is solvent in weaken acids and methanol, chloroform and for all intents and purposes insoluble in water 7.2 phosphate cradle, and marginally dissolvable in weaken acids having pH 3.3 or underneath. Dipyridamole tablet USP, for oral organization, contains 25 mg, 50 mg, or 75 mg Dipyridamole, USP and contains the accompanying latent fixings: colloidal silicon dioxide, hypromellose, lactose anhydrous, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, propylene glycol, stearic corrosive, sodium starch glycolate, and titanium dioxide. For IV organization Dipyridamole infusion 5 mg ml-1 USP. Dipyridamole represses the take-up of adenosine into platelets, endothelial cells and erythrocytes in vitro and in vivo; the restraint happens in a portion subordinate way at remedial fixations (0.5 to 1.9 mcg/mL). This restraint brings about an expansion in nearby convergences of adenosine which follows up on the platelet A2-receptor consequently invigorating platelet adenylate cyclase and expanding platelet cyclic-3',5'- adenosine monophosphate (cAMP) levels. By means of this instrument, platelet total is restrained in light of different boosts, for example, platelet initiating factor (PAF), collagen and adenosine diphosphate (ADP).

Dipyridamole is a great platelet inhibitor, this impact because of the restraint of the adenosine transporter prompts an expansion in cAMP, an inhibitor of platelet total (Lugnier et al., 1986; Gresele et al., 1986). As of late, in any case, a few investigations have proposed that dipyridamole additionally has helpful properties to vasculature, for example, restraint of multiplication, cancer prevention agent (Luliano et al., 1989) and mitigating properties (Al-Bahrani et al., 2007). Dipyridamole is frequently utilized in clinical counteraction and treatment of thrombosis and cerebrovascular illness, which are exceptionally regular in the old. Regardless of whether the medication is administrated in single or in blend with other pertinent medication, for example, ibuprofen, investigation of the plasma focus time profile for dipyridamole is of basic clinical significance for its sound solution. In this manner, quick, specific, monetarily modest and advantageous logical strategies are required for the assurance of dipyridamole in human plasma. [1-2]

DPM is available individual or in combinations which are approved in various national and international markets and in various dosage as seen in online resources. (rectified in Table 1 and Table 2) [5-6]

Figure 1: Chemical structure of Dipyridamole

Table 1 Drug profile of Dipyridamole

Drug Name

Dipyridamole

Category

Anticoagulants

Antiplatelet agents

Chemical formula

C24H40N8O4

IUPAC Name

2-({6-[bis(2-hydroxyethyl) amino]-4,8-bis(piperidin-1-yl)- [1,3] diazino[5,4-d] pyrimidin-2-yl} (2-hydroxyethyl) amino) ethan-1-ol

Molecular weight

504.626 g/mol

Melting point

163 ℃.

Solubility

soluble in dilute acids and methanol, chloroform and practically insoluble in water

Half life

Alpha half-life 40 mins

Beta half-life 10 hours

Pka value

Strongest acid- 14.97

Strongest base- 6.59

log P value

log P 1.52

log P 1.81

log S value

-2.7

Mechanism of Action:

Dipyridamole likely restrains both adenosine deaminase and phosphodiesterase, forestalling the debasement of cAMP, an inhibitor of platelet work. This height in cAMP hinders the arrival of arachidonic corrosive from film phospholipids and lessens thromboxane A2 movement. Dipyridamole likewise legitimately invigorates the arrival of prostacyclin, which actuates adenylate cyclase action, along these lines raising the intraplatelet grouping of cAMP and further restraining platelet accumulation. [3-4]

Table 2 Marketed formulation of Dipyridamole single

Name

Dosage form

Strength

Route

Labeller

Dipyridamole

Tablet, film coated

25 mg/1

Oral

Avera McKennan Hospital

Dipyridamole

Tablet, film coated

50 mg/1

Oral

Zydus Pharmaceuticals (USA) Inc.

Dipyridamole

Injection

5 mg/1mL

Intravenous

Teva Parenteral Medicines, Inc.

Dipyridamole

Tablet, film coated

50 mg/1

Oral

Glenmark Generics, Inc. USA

Dipyridamole 25 Tab 25mg

Tablet

 

Oral

Pro Doc Limitee

Dipyridamole 50 Tab 50mg

Tablet

 

Oral

Pro Doc Limitee

Dipyridamole 75 Tab

Tablet

 

Oral

Pro Doc Limitee

Dipyridamole

Solution

5 mg/1mL

Intravenous

Anazao Health Corporation

Table 3: Marketed formulation of Dipyridamole in combination

Name

 

Dossage Form

Route

Labeller

Aggrenox

Dipyridamole (200 mg/1) + Acetylsalicylic acid (25 mg/1)

Capsule

Oral

Rebel Distributors

Aggrenox

Dipyridamole (200 mg/1) + Acetylsalicylic acid (25 mg/1)

Capsule, extended release

Oral

Boehringer Ingelheim Pharmaceuticals, Inc.

Aggrenox

Dipyridamole (200 mg) + Acetylsalicylic acid (25 mg)

Capsule, extended release

Oral

Boehringer Ingelheim (Canada) Ltd Ltee

Aggrenox

Dipyridamole (200 mg/1) + Acetylsalicylic acid (25 mg/1)

Capsule, extended release

Oral

Carilion Materials Management

Aggrenox

Dipyridamole (200 mg/1) + Acetylsalicylic acid (25 mg/1)

Capsule

Oral

Physicians Total Care, Inc.

Asasantine Cap

Dipyridamole (75 mg) + Acetylsalicylic acid (330 mg)

Capsule

Oral

Boehringer Ingelheim (Canada) Ltd Ltee

Aspirin and Dipyridamole

Dipyridamole (200 mg/1) + Acetylsalicylic acid (25 mg/1)

Capsule, extended release

Oral

Teva Pharmaceuticals USA, Inc.

Aspirin and Dipyridamole

Dipyridamole (200 mg/1) + Acetylsalicylic acid (25 mg/1)

Capsule, extended release

Oral

Slate Run Pharmaceuticals, Llc

Aspirin and Dipyridamole

Dipyridamole (200 mg/1) + Acetylsalicylic acid (25 mg/1)

Capsule, extended release

Oral

NorthStar Rx LLC

Aspirin and Dipyridamole

Dipyridamole (200 mg/1) + Acetylsalicylic acid (25 mg/1)

Capsule, extended release

Oral

Dr. Reddy's Laboratories Inc

Analytical Profile for Dipyridamole:

Writing overview uncovers that there are number pharmaceutical strategies for estimation of Dipyridamole is accounted for alone or in mix. Greatest strategy revealed synchronous judgments with Aspirin. Adequate Literature was found for examination of Dipyridamole in human's plasma, mass and in different measurements structure by UV Spectrophotometry, HPTLC, HPLC, LCMS/MS, UPLC strategies.

  1. HPLC analysis:

By surveying the literature 1997-2019 it is revealed that HPLC equipped with UV visible, PDA and VWD detection has been the widely applied technique for the analysis of Dipyridamole and its metabolites. However, most of the HPLC experiments were done on C18 columns. The estimation of Dipyridamole by use HPLC is found in combination with Aspirin. The investigation of Dipyridamole using variable mobile phases, columns and instrumentation is precisely presented in article.

Data presented in Table no: 4 enlightens about dosage form, details of instrument, analytical column and other conditions like temperature, mobile phase pH, flow rate, selected wavelength detector used.

Table 4 High-Performance Liquid-Chromatography Methods for Estimation of DPM

Sr. no.

Drug

Dosage

Method

Stationary phase

Mobile phase

Detection/Detector

Rt / FR

Ref

1

Dipyridamole

Tablet

RP-HPLC

Targa C8 column i.e., (250 X 4.6 mm 5 μm particle size) column

Consists of acetonitrile and potassium dihydrogen phosphate buffer (pH3.0) in the ratio of

35:65 %

282nm.

UV Detector

Rt: 4.2 min

FR: 1.2 ml/min

 

7

2

Dipyridamole

Reference

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  4. https://step1.medbullets.com/ assessed on 16.04.2020
  5. https://www.drugbank.ca/drugs/DB00975, assessed on 16.04.2020
  6. https://pubchem.ncbi.nlm.nih.gov/ assessed on 16.04.2020
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  10. Reddy, D.V., Sreelatha, P. and Devi, B.R., 2015. A rapid novel RP-HPLC stability indicating assay method development and validation of dipyridamole in dipyridamole extended release capsules. Anal Chem, 15(4), pp.140-150.
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Photo
Shubham Madhe
Corresponding author

Department of Pharmaceutical Quality Assurance, Shri Sai College of Pharmacy Khandala, Tal. Vaijapur, Dist. Chh. Sambhajinagar 431116

Photo
P. P. Udapurkar
Co-author

Department of Pharmaceutical Quality Assurance, Shri Sai College of Pharmacy Khandala, Tal. Vaijapur, Dist. Chh. Sambhajinagar 431116

Photo
R. R. Tagad
Co-author

Department of Pharmaceutical Quality Assurance, Shri Sai College of Pharmacy Khandala, Tal. Vaijapur, Dist. Chh. Sambhajinagar 431116

Shubham Madhe*, P. P. Udapurkar, R. R. Tagad, A Concise Review on Analytical Profile of Dipyridamole as Coronary Vasodilator, Int. J. Med. Pharm. Sci., 2026, 2 (3), 349-357. https://doi.org/10.5281/zenodo.19135537

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