Chapter-4 Domperidon INTRODUCTION Domperidon (DMPN) is a...
Transcript of Chapter-4 Domperidon INTRODUCTION Domperidon (DMPN) is a...
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Chapter-4 Domperidon
Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 102
INTRODUCTION
Domperidon (DMPN) is a D2 antagonist, chemically related to
haloperidol, but pharmacologically related to metoclopromide. It has
lower ceiling antiemetic and prokinetic actions. Unlike metoclopromide its
prokinetic action is not blocked by atropine and is based only on D2
receptor blockade in upper GI tract. DMPN crosses blood brain barrier
less readily and rarely causes the extra pyramidal side effects [1-5].
Structure
N
NH
NN
NHO
O
Cl
DMPN, [5–chloro-1-{1-[3-(2-oxobenzenimidazolin–1–yl)-propyl]-4
piperidyl} benzimidazolin-2-one] is a white, or almost white powder. It
is used as an anti-emetic and to control gastrointestinal effects of
dopaminergic drugs in the management of Parkinsonism [6-8].
Formula - C22H24ClN5O2
Solubility - Practically insoluble in water, slightly soluble in
alcohol. It is soluble in dimethylformamide [9]
Mol. Wt. - 425.11 g/mol
Brand name - DMP (D1), Dompet (D2), Domestol (D3)
Identification - Identification of pure drug is performed by
FT-IR (Shimadzu 8400s) and compared
with standard one available in Indian
pharmacopeia.
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Fig. 4.1: Reference IR spectrum of DMPN
Table 4.1: Characteristics absorption frequencies for identification of
pure DMPN
S. No. Types of Vibrations Frequency (cm-1)
1. Ar. C – H Stretching 3072.71
2. C – Cl 732.97
3. N – H Bending 1489.1
4. C = O Stretching 1716.7
5. C – N Stretching 1332.21
6. C = C Stretching 1624.12
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Fig
. 4.2
: IR
spectr
um
of
pure
DM
PN
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Bioavailability - DMPN after oral dosing undergoes extensive gastric
and hepatic first pass metabolism resulting in low bioavailability
(15%) which therefore may not minimize the rate of vomiting [10].
Protein binding - 91-93%
Metabolism - DMPN undergoes first-pass and gut wall metabolism.
Through hydroxylation and oxidative N-dealkylation, DMPN is
metabolized to hydroxyl DMPN and 2, 3-dihydro-2-oxo-1-H-benzimidazole
-1-propionic acid, respectively [11-12].
Excretion - Breast Milk, renal
History - Janssen Pharmaceutical has brought DMPN before the FDA
several times in the last two decades, with the most recent effort in
the 1990s. Numerous U.S. clinical drug trials have demonstrated its
safety and efficacy in dealing with gastro paresis symptoms, but the
FDA turned down Janssen’s application for DMPN, even though the
FDA’s division of gastrointestinal drugs had approved DMPN.
Adverse effect - Some of the side effects associated with DMPN are an
extensive of its dopamine antagonist properties. A majority of these
side effects resolve spontaneously during continued therapy or are
tolerated. However, more serious of troublesome side effects (e.g.
galactorrhea, gynecomastia, or menstrual irregularities) can be dose-
related and will respond to lowering the dose or discontinuing therapy [13].
The benzimidazole derivative is a dopamine D2 receptor
antagonist that has been marketed in Europe and other countries as a
prokinetic and antiemetic since 1978 [14]. Its localization outside the
blood – brain barrier and antiemetic properties has made it is a useful
adjunct in therapy for Parkinson’s disease. There has been
rehabilitated curiosity in antidopaminergic prokinetic agents since the
abandonment of cisapride, a 5-HT4 agonist, from the market. DMPN is
also as a prokinetic negotiator for treatment of upper gastrointestinal
motility disorders. It continues to be an attractive alternative to
metoclopramide because it has fewer neurological side effects [15].
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Patients receiving DMPN or other prokinetic agents for diabetic
gastropathy or gastroparesis should also be managing diet, lifestyle,
and other medications to optimize gastric motility.
Bio–Analytical methods -
Several methods have been reported for DMPN determination,
including spectrophotometric [16-18], and High Performance Liquid
Chromatography [19-26].
Sadana et al., have given a HPLC method for estimation of
DMPN in pharmaceutical preparations [27].
Zarapkar et al., have determined DMPN by high performance
thin layer chromatography in pharmaceutical preparations [28].
Mohan et al., have described an extractive spectrophotometric
determination of DMPN in its pharmaceutical dosage forms [29].
Mohemend et al., have described first derivative UV-visible
spectrophotometric assay of DMPN [30].
Rao et al., have described a spectrophotometric method for the
estimation of DMPN and omeprazole [31].
Abdelal et al., have reported method development and validation
for the simultaneous determination of cinnarizine and DMPN in
pharmaceutical preparations by capillary electrophoresis [32].
Sivakumar et al., have developed a validated reverse-phase
HPLC method for simultaneous determination of DMPN and
pantaprazole in pharmaceutical dosage forms [33].
Kakde et al., have reported a spectrophotometric method for
simultaneous estimation of DMPN in pharmaceutical formulations
[34].
Amin et al., have reported spectrophotometric methods for the
determination of anti-emetic drug in bulk and pharmaceutical
preparations [35].
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Nema et al., have described a spectrophotometric method for the
determination of DMPN on the basis of redox reaction [36].
The BP 1998 reported a titrimetric method [37]. This titrimetric
procedure requires about 0.25 g to provide accurate results, yet, no
work has been performed to use a redox reaction for the determination
of DMPN. The purpose of the present study was to apply redox
reaction in presence of polymeric micellar media to develop simple,
accurate, sensitive and reproducible methods that can be used in
laboratories where modern and expensive apparatus, such as that
required for GLC, HPLC is not available.
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The therapeutic efficacy of a drug product intended to be
administered by oral route mainly depends on its absorption by the
gastrointestinal tract. However for a drug substance to be absorbed, it
needs to be solubilized. Numerous works have been carried out in
order to modify the dissolution kinetics of poorly water-soluble drugs
to improve their bioavailability. DMPN is a D2 antagonist used as anti-
emetic has poor aqueous solubility (0.986 mg/mL) [38]. Dissolution
rate test forms an essential tool in pharmaceutical product
development as well as in quality control. Dissolution characteristics
of a dosage form have a direct bearing on its efficacy especially when
the medication is poorly soluble or insoluble in aqueous fluids such as
DMPN. The use of hydrophilic polymers as carriers for the dissolution
enhancement of poorly water soluble drug is increasing [39-40]
various hydrophilic carriers such as polyethylene glycol [41]
polyvinylpyrrolidone [42-43] and sugars [44] have been investigated
for improvement of dissolution characteristics and bioavailability of
poorly aqueous soluble drugs.
Determination of λmax of pure DMPN drug:
10 g/mL of pure DMPN in methanol was prepared. The
prepared solution was scanned in UV region (200-400 nm) to get
absorbance maxima (Fig. 4.3).
Fig. 4.3: Determination of λmax of DMPN
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Verification of Beer’s Lambert law:
Stock solution was prepared by dissolving accurate 100 mg of
substance (DMPN) in 10 mL of methanol in 100 mL calibrated flask.
Then made up to the mark with distilled water then above stock
solution was further diluted to get solution containing 0.1 µg/mL
to 50 µg/mL and measure the absorbance at its max 285 nm
against water as blank. A plot of Beer’s law (Absorbance vs
concentration) gave a highly precise, reproducible straight line that
passed through the origin with satisfactory statistical parameters.
Beer’s law obeyed in the concentration range of 1–50µg/mL (Fig.4.4).
Fig. 4.4: Verification of Beer’s Lambert law
Solubility measurements:
100 mg DMPN was added to 50 mL of each solvent such as
0.5% PEG 400, CTAB, SLS, PEG 4000 and PVP 44000 taken in flask
and the mixture were shaken at 37ºC ± 0.5ºC in a magnetic stirrer.
5mL aliquot was withdrawn at 1 hour interval and filtered immediately
by using a 0.45 m syringe filter. The filtered sample were diluted
suitably and assayed for DMPN by UV-visible spectrophotometer at 285nm.
Shaking continued until two consecutive estimations were the same.
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Table 4.2: Solubility of DMPN in different media
S.
No. Sample
Wt. of
drug
(mg)
Overall
volume
(mL)
Abs.
Solubility
increase
in fold
1. DMPN + Distilled water 100 50 0.156 1.00
2. DMPN + 0.5 % CTAB 100 50 0.926 5.93
3. DMPN + 0.5 % PEG 400 100 50 0.630 4.08
4. DMPN + 0.5 % PEG 4000 100 50 0.304 1.95
5. DMPN + 0.5 % SLS 100 50 0.310 1.99
6. DMPN + 0.5 % PVP 44000 100 50 1.553 9.96
Fig. 4.5: Solubility determination of DMPN in different fluids
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Polymeric surfactants (PVP 44000) form nanoscopic core-shell
structures above the critical micellar concentrations. In the
hydrophobic drugs while the hydrophobic part serves as reservoirs for
hydrophobic drugs, the hydrophilic part serves as interface between
the bulk aqueous phase and the hydrophobic domain. This unique
architecture enables polymeric micelles to serve as nanoscopic depots
or stabilizers for poorly water-soluble compounds.
Fig. 4.6: Solubilization of drugs in surfactant micelles, depending on
the drug hydrophobicity. The black bold lines (▬) represent the drug
at different sites in the micelle. The black circles represent the
surfactant heads, the black bold curve lines represent surfactant
heads consisting of PVP and the light black curved lines represent the
surfactant tails.
In Vitro dissolution study:
The three different brands of DMPN have been purchased from
local market. For the sake of convenience these are abbreviated as -
1. DMP (D1)
2. Dompet (D2)
3. Domestol (D3)
Dissolution study is particularly important for insoluble or low
solubility drugs, where absorption is dissolution-rate limited. At the
same time, development of a dissolution method for this group of drug
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is very challenging. In continuation of our earlier work on dissolution
study [45-46], this work describes dissolution quality assessments, in
the evaluation of the rate of dissolution for a water insoluble drug
DMPN.
1. Apparatus : Electrolab TDT - 08L USP
2. Dissolution medium: 0.5 % PVP 44000 in water
3. Rotation speed: 75 rpm
4. Preparation of DMPN standard solution: 1.12 mg DMPN was
weighed precisely and transferred in 100 mL volumetric flask
and diluted up to the mark with dissolution media. 5 mL of the
above solution is further diluted up to 50 mL with dissolution
media i.e. 0.5 % aqueous PVP.
5. Test preparation: The dissolution of DMPN from commercial
formulations (10 mg) was studied in 900 mL of dissolution
medium using a (Basket method) USP-29 at Electro lab TDT-
08L dissolution rate test apparatus. Dissolution medium (900
mL) was maintain at 37°± 0.5°C and agitated at a speed of 75
rpm under sink condition, withdrawal the 5 mL of sample at
each time interval from the dissolution apparatus and
withdrawal volume replaced by fresh dissolution media to
maintain the sink condition, filtered the withdrawn sample and
prepared appropriate dilution. The sample solution was
analyzed at 285 nm by UV-Vis. spectrophotometer.
6. Time point: Dissolution amount was measured separately at
60, 120, 180, 240, 360, 480 and 600 minutes.
claim Lable
100
100
potency
dilution Test
dilution Std.
Std. of Absorbance
Sample of Absorbance
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Table 4.3: Sample absorbance at different time intervals
S.
No. Time (min)
Absorbance
D1 D2 D3
1. 60 0.054 0.045 0.039
2. 120 0.072 0.057 0.096
3. 180 0.090 0.123 0.132
4. 240 0.118 0.135 0.144
5. 360 0.156 0.147 0.156
6. 480 0.183 0.216 0.210
7. 600 0.286 0.285 0.287
Standard Abs. 0.291
Table 4.4: % drug release of various formulations in polyvinyl- pyrrolidone at different time
S.
No. Time (min)
% drug release
D1 D2 D3
1. 60 18 15 13
2. 120 24 19 32
3. 180 30 41 44
4. 240 40 45 48
5. 360 50 49 52
6. 480 61 72 70
7. 600 95 94 95
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Table 4.5: log time, square root of time and log % of drug release
S.
No.
Time
(min) log time
Square
root of
time
log % drug release
D1 D2 D3
1. 60 1.77 7.74 1.25 1.17 1.11
2. 120 2.079 10.95 1.38 1.27 1.36
3. 180 2.25 13.41 1.47 1.61 1.64
4. 240 2.38 15.49 1.59 1.65 1.68
5. 360 2.55 18.97 1.71 1.69 1.71
6. 480 2.68 21.90 1.78 1.85 1.84
7. 600 2.77 24.49 1.97 1.97 1.98
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Fig. 4.7: Dissolution profile (n=3) of three commercial products of
DMPN in polymeric micellar media (Zero order plot)
Fig. 4.8: Regression plot for zero order
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Fig. 4.9: First order plot
Fig. 4.10: Regression plot for first order
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Fig. 4.11: Korsmeyer Plot
Fig. 4.12: Regression plot for Korsmeyer model
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Fig. 4.13: Higuchi plot
Fig. 4.14: Regression plot for Higuchi model
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Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 119
Table 4.6: Kinetic parameters for D1
S. No. Time
(min)
Rate Constant (k)
First order Korsmeyer Higuchi Zero order
1. 60 3.92 × 10-2 1.13 × 10-2 1.03 0.133
2. 120 1.99 × 10-2 9.41 × 10-3 1.27 0.116
3. 180 1.36 × 10-2 8.91 × 10-3 1.49 0.111
4. 240 1.06 × 10-2 9.75 × 10-3 1.93 0.125
5. 360 7.53 × 10-3 9.60 × 10-3 2.21 0.116
6. 480 6.01 × 10-3 9.25 × 10-3 2.32 0.106
7. 600 - 1.25 × 10-2 3.51 0.143
r2 0.9721 0.9545 0.9048 0.9564
Slope (n) 0.67
Table 4.7: Kinetic parameters for D2
S. No. Time
(min)
Rate Constant (k)
First
order Korsmeyer Higuchi Zero order
1. 60 3.90 × 10-2 6.04 × 10-3 0.77 0.10
2. 120 1.97 × 10-2 4.40 × 10-3 0.91 0.08
3. 180 1.42 × 10-2 6.88 × 10-3 2.38 0.17
4. 240 1.09 × 10-2 6.00 × 10-3 2.3 0.15
5. 360 7.44 × 10-3 4.73 × 10-3 2.10 0.11
6. 480 6.80 × 10-3 5.52 × 10-3 2.87 0.13
7. 600 - 6.10 × 10-3 3.51 0.14
r2 0.8698 0.970 0.9351 0.9559
Slope (n) 0.79
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Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 120
Table 4.8: Kinetic parameters for D3
S. No. Time
(min)
Rate Constant (k)
First order Korsmeyer Higuchi Zero order
1. 60 3.80 × 10-2 4.85 × 10-3 0.64 0.08
2. 120 2.00 × 10-2 4.88 × 10-3 1.93 0.12
3. 180 1.40 × 10-2 6.72 × 10-3 3.28 0.20
4. 240 1.10 × 10-2 5.80 × 10-3 2.98 0.16
5. 360 8.00 × 10-3 4.52 × 10-3 2.84 0.12
6. 480 7.00 × 10-3 4.95 × 10-3 3.37 0.13
7. 600 - 5.51 × 10-3 4.01 0.14
r2 0.8262 0.9579 0.9355 0.9392
Slope (n) 0.81
RESULTS AND DISCUSSION
The solubility of DMPN was determined at 37ºC ± 0.5ºC in
different fluids is listed in Table 4.2. Surfactant greatly increases the
solubility of DMPN. The surprising increase in solubility of DMPN by
9.96 fold is found in 0.5% PVP (Fig. 4.5).
Mechanism and kinetics of drug release - To know the mechanism
of drug release from these formulations, the data were treated
according to zero-order (cumulative amount of % drug release vs. time
and its regression plots are shown in Fig. 4.7 and 4.8), first order (log
cumulative % of drug release vs time and its regression plots in Fig.
4.9 and 4.10) Korsmeyer plot (log cumulative % of drug release vs log
time and its regression plots in Fig.4.11 and 4.12) and Higuchi’s
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(cumulative % of drug release vs. square root of time and its
regression plots in Fig. 4.13 and 4.14) equations. As can be revealed
from Fig.4.7, neither of the tablets followed a complete zero order
release nor first order pattern. Diffusion is related to transport of
drug from the dosage matrix in to the in vitro study fluids depending
on the concentration. As gradient varies, the drug is released, and the
distance for diffusion increases, which is referred as Korsmeyer
kinetics. In our experiment, the in vitro release profile of DMPN from
all the brands could be best expressed by Korsmeyer equation, as the
plot showed high linearity (r2 > 0.95). The slope of the regression line
from Korsmeyer plot indicates the rate of drug release. The
comparative Korsmeyer release rates for different brands are
presented in Fig. 4.11. Table 4.6, 4.7 and 4.8 reveal that the k
obtained from Korsmeyer-Peppas model shows better result with high
correlation coefficient (r2 = 0.954-0.970).
The Korsmeyer-Peppas model is used to analyze drug release
from pharmaceutical dosage forms when the release mechanism is not
well known or when more than one type of release phenomena is
involved. The exponent, termed the release exponent n, was studied by
Peppas and coworkers to characterize different drug release
mechanisms from thin films. They noted that profile with n = 0.5
exhibited a drug release mechanisms controlled by Fickian diffusion,
while drug release rate was independent of time and controlled by a
swelling mechanism when n = 1. In the current study, the value of
release rate exponent (n), ranged between 0.67 – 0.81. Values of n
between 0.5 and 1.0 were regarded as an indicator for the
superposition of both phenomena, and the drug release mechanism
was termed anomalous (non-Fickian) transport.
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Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 122
Preparation of stock solution of pure DMPN drug:
Stock solution of DMPN was prepared by dissolving 425 mg in
1:1 acetic acid and water and made up to the mark in 100 mL
volumetric flask. The above stock solution was further diluted to get a
working standard solution.
Preparation of different solutions for calibration curve in
presence of V(V):
It was difficult to select the suitable concentration of DMPN
because at CMC of PVP, below the drug concentration (4×10-5)
reaction did not occur. Similarly at higher concentration of drug
(1×10-2) reaction mixture precipitated.
Different volumes of the drug solutions (in range 0.04 – 4.0 mL)
prepared above were accurately measured into different 10 mL
volumetric flask. After the addition of 0.1 mL of V(V), 0.3 mL of PVP (to
get the solution of 3 × 10-6 M) and 1.5 mL (18 M) were successively
added and diluted up to the mark with water. The contents of each
flask were mixed well. Initially yellow color of reaction mixture slightly
changes to pink then finally turns to purple. The absorbance of light
pink colored species formed. Absorbance of each solution was then
measured after 15 min. at 355 nm. A calibration graph was
constructed by plotting the absorbance against the concentration of
the drug (Fig.4.16).
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Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 123
Fig. 4.15: Absorption maxima of V(V) and V(IV)
Table 4.9: Reaction mixture
Sample
Concentration (M)
Stock solution (M) Required (M)
[DMPN] 0.01 0.00002-0.004
[V(V)] 0.01 0.0001
[H+] 18 1.5
[PVP 44000] 0.0001 3 × 10-6
Overall volume 10 mL
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Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 124
Table 4.10: Absorbance of standard solution of pure drug at different concentrations in presence of V(V)
S. No. Concentration (M) Absorbance (at 355 nm)
1. 0.00004 0.552
2. 0.00006 0.554
3. 0.00008 0.555
4. 0.0002 0.560
5. 0.0004 0.568
6. 0.0005 0.574
7. 0.0008 0.583
8. 0.001 0.589
9. 0.002 0.589
10. 0.003 0.587
11. 0.004 0.584
y = 0.0001x + 0.5509
R2 = 0.9943
0.55
0.555
0.56
0.565
0.57
0.575
0.58
0 50 100 150 200 250
Concentration ( g/mL)
Absorb
an
ce
Fig. 4.16: Calibration curve of pure drug in presence of V(V)
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Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 125
Preparation of sample solutions:
For the determination of DMPN in tablets, the above method
was used with no modification. About ten tablets were grinded into
finely divide powder. An accurately amount equivalent to 425 mg was
weighed and dissolved in 1:1 acetic acid and water. The solution was
shaken well for 30 min. to ensure a homogenous solution. The residue
was removed through 0.45 m syringe filter and washings were taken
into a 100 mL standard flask and diluted with 1:1 acetic acid and
water. Then three concentrations of DMPN within the linearity range
were selected i.e. 0.00008, 0.0002 and 0.0004.
Table 4.11: Absorbance of sample solutions of different marketed
brands at three concentrations
S.
No.
Concentration
(M)
Absorbance (355 nm)
Pure drug D1 D2 D3
1. 0.00008 0.555 0.551 0.561 0.559
2. 0.0002 0.56 0.556 0.571 0.555
3. 0.0004 0.568 0.567 0.573 0.565
Table 4.12: Recovery Study
S. No. Label claim in mg Amount of drug found (%)
D1 D2 D3
1. 10 99.27 101.08 100.72
2. 10 99.28 101.96 99.10
3. 10 99.82 100.88 99.47
Average Recovery (%) 99.47 101.31 99.77
Standard Deviation 0.312 0.576 0.846
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Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 126
RESULTS AND DISCUSSION
Spectral studies:
The spectrum of reference pure drug of DMPN in organic solvent
shows an absorption band at 285 nm. The addition of acidic solution
of V(V) to the drug solution causes change in the absorption spectrum
with new characteristic band peaking at 355 nm. The equilibrium is
attained in 10 minute. Therefore, a kinetically based spectrophotometric
method was developed for the quantitative determination of DMPN by
measuring the increase in absorbance at 355 nm as a function of
time.
Linearity:
Beer’s law obeyed in the concentration range of 17–212 g/mL.
Application of the method to tablets:
The accuracy of the proposed method was checked by
performing recovery experiments. For this, a known amount of the
pure drug was added to pre-analysed dosage forms and then
determined by the recommended procedure. The result obtained in
table 4.12 showed that the mean recovery and standard deviation
were in the range of 99.77 ± 0.312 to 101.31 ± 0.576 respectively.
These results also suggested that there is no interference from the
common excipients present in dosage forms.
Optical characteristics such as Beer’s law limits, molar
absorbitivity and Sandell’s sensitivity for DMPN, are given in table
4.13.
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Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 127
Table 4.13: Quality Control Parameters
S. No. Parameters DMPN
1. max (nm) 355
2. Beer’s Range ( g/mL) 17 - 212
3. Molar Absorbtivity (L mol-1 cm-1) 1.28 × 105
4. Sandell’s Sensitivity (µg cm-2) 0.0033
5. Regression equation 0.994
6. Intercept 0.5509
7. Slope 0.0001
8. Limit of Detection (µg/mL) 2.62 ×102
9. Limit of Quantization (µg/mL) 8.75 × 102
10. Standard Deviation of calibration line 0.008
PROPOSED MECHANISM
The proposed method is based on the formation of an
intermediate complex. The reaction proceeds through the reduction of
V(V) to V(IV) and the subsequent formation of intensive pink-brownish
color complex.
The absorption spectrum of the colored species in the proposed
method at suitable conditions recovered in the general procedure
show a characteristic max at 355 nm (Fig. 4.15).
In conclusion, I have found that DMPN is mainly N-Dealkylated
by V(V) which is confirmed by LC-MS (Fig. 4.17).
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Fig. 4.17: Mass Spectrum of DMPN + V(V)
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VO2+ + H3O V(OH)32+
V(OH)32+ + HSO4 [V(OH)3HSO4]
+-
[A]
N
NH
O
Cl
N
N
O
N
H
+ [A]
Cl
N
N
O
NN
NH
OHHOSO3OH V OH
OH
+
DMPN
Cl
N
N
O
NN
NH
OH
HOSO3OH V OH
OH
+
[B] Intermediate complex
[B] + Dn
Dn
[C] Adduct
Fast step N- dealkylation
N
NH
O
COOH
Cl
N
N
O
NH
H
+
2,3- dihydro, 2- oxo 1H- benzimidazole-1-
propionic acid (m/z - 193)
5- chloro 4-Piperidinyl 1,3-
dihyrobenzimidazol-2-one
(m/z - 252)
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Chapter-4 Domperidon
Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 130
CONCLUSION
The proposed method was successfully applied to determine
DMPN in their pharmaceutical preparation. Importantly, no any
method is available yet today for its determination.
The proposed method is simpler, less time consuming and more
sensitive than official method [47] (based on titrimetry and
potentiometry).
Although the color development at room temperature required
1h for completion, this can be shortened to 20 min. by
introducing polymeric surfactant.
The proposed method advantageous over other reported UV-
visible spectrophotometric method with respect to their higher
sensitivity with permits of the determination of up to 17 g/mL.
Simplicity, reproducibility, precision, accuracy and stability of
colored species for a week noted advantages.
No interference from associated excipients, additives and
degraded products were observed.
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Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 131
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