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Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 135
INTRODUCTION
Over the past decade several new drugs have been introduced to
treat hypertension, thus providing alternative options for treatment.
Many authorities and expert organizations worldwide, however, still
recommend thiazide diuretics and blockers as first line drugs for the
treatment of hypertension [1].
The selection of a new antihypertensive agent or a modification
of the commonly used stepped care approach to antihypertensive
treatment, however, presupposes that the new drug has been proved
to be superior, or at least equivalent to, the standard treatment. Thus
there is a need for long term studies of sufficient numbers of patients
to compare the antihypertensive efficacy, tolerability, and adverse
drug reactions of the new therapeutic regimen with the standard
treatment [2].
Hydrochlorothiazide (HCTZ) is widely prescribed diuretic, used
in congestive heart failure and hypertension [3]. In healthy fasting
volunteers the gastrointestinal uptake of the compound approximates
70 % and it is linear over the dose range 5-75 mg [4-6].
Structure
NH
NHSNH
2SO
2
Cl
OO
HCTZ, (6-chloro-3,4-dihydro-2H-1,2,4-benzo-thiadiazines- 7-
sulfonamide 1,1-dioxide) [7-8] is a widely prescribed diuretic. It is
indicated for the treatment of edema, control of essential hypertension
and management of diabetes insipidus [9-11].
Formula – C7H8ClN3O4S2
Solubility – Soluble in acetone, sparingly soluble in
ethanol (95 %), very slightly soluble in water.
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 136
It dissolves in dilute solution of alkali
hydroxides [12].
Mol. Wt. – 297.73 g/mol
Brand name – Hydrazide(H1), Aquazide(H2), Xenia(H3)
Identification – Identification of pure drug is performed by
FT-IR (Shimadzu 8400s) and compared with
standard one available in Indian
pharmacopeia [13].
Fig. 5.1: Reference IR Spectrum of HCTZ
Table 5.1: Characteristics absorption frequencies for identification
of pure HCTZ
S. No. Types of Vibrations Frequency (cm-1)
1. Ar. C – H Stretching 3066.92
2. Ar. C = C Stretching 1600.97
3. Ar. N – H Stretching 3263.66
4. N – H Stretching in NH2 3169.15
5. Asymmetric Stretching SO2 1330.93
6. Symmetric Stretching SO2 1180.47
7. S – N Stretching 908.5
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 137
Fig
. 5.2
: IR
spectr
um
of
pure
HC
TZ
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 138
Bioavailability - About 65-70%
Protein binding - 67.9%
Metabolism - HCTZ is not modified by organic biochemical processes.
Half life - 5.6 and 14.8 hrs.
Excretion - Elimination of HCTZ is mainly due to renal clearance that
occurs in about 320 mg/min. It is excreted unchanged in the urine.
HCTZ crosses the placental barrier and appears in breast milk.
History - Research in sulfonamide chemistry has brought a rich yield
of valuable therapeutics. One of the great successes was the discovery
of the benzothiadiazines as potent diuretics of low toxicity [14]. In
1958 De Stevens et al. [15] reported on the condensation product of 4-
amino-6-chloro-3, 5-disulfonamide and formaldehyde which was
found to be identical with the hydrogenation product of chlorothiazide
[16] and which soon became a widely used saluretic – Hydrochlorothiazide.
Adverse effects - The thiazide diuretic may cause a number of
metabolic disturbances. HCTZ may induce hyperglycemia and may
aggravate pre-existing diabetes mellitus. Thiazide diuretics increase
the concentrations of cholesterol and triglycerides in plasma by
unknown mechanism.
Uses - Hydrochlorothiazide is a diuretic which reduces the reabsorption
of electrolyte from the renal tubules.
Used to treat hypertension disease to manage the oedema due
to mild-to-moderate congestive heart failure. Oedema due to chronic
hepatic or renal disease may also respond favorably. It may also used
in patients with diabetes insipidus, due to a paradoxical effect.
Bio–Analytical methods -
Several analytical methods including LC-UV [17-18], spectro-
photometry and HPLC have already been reported for its determination,
either alone or in combination with other drugs [19-48].
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 139
Gotardo et al. have described diffuse reflectance spectroscopic
method for the determination of HCTZ in tablet formulations [49].
Kadam et al. have been reported quantitative analysis of
valsartan and HCTZ in tablets by high performance thin-layer
chromatography with ultraviolet absorption densitography [50].
Qutab and co-workers have described a simple and sensitive
LC-UV method for simultaneous analysis of HCTZ and candesrtan
cilexetil in pharmaceutical formulations [51].
Maillard et al. studied the fixed dose combination of telmisartan
and HCTZ to treat hypertension [52].
Satana et al. have determined simultaneously HCTZ and valsartan
in tablets by first-derivative ultraviolet spectrophotometry and LC
method [53].
Jordo et al. have been studied bioavailability and disposition of
metoprolol and HCTZ combined in one tablets and of separate doses
of HCTZ [54].
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 140
Pharmacodynamic concerns the relationship of formulations
and pharmacological effects, especially how solid dosage forms are
absorbed in vivo. Complicated factors are involved, among which, drug
disintegration and dissolution are very important ones. Due to its low solubility in water, the Federal Register of the
FDA categorizes it as questionable bioavailability tests [55].
Formulations of different brands have different types and/or amount
of adhesive, disintegrates, lubricants, or other excipients, as well as
different compression forces which affect the disintegration and
dissolution rate of a given formulation. Substantial related research
has been published such as Ibrahim H. G. who studied the influence
of compression forces on the dissolution profile of HCTZ and
phenylbutazone. It is proven that dissolution is positive proportional
to the logarithm of compression forces [56]. Tablet intensity is also
functionality relation with compression forces, so it is feasible to
establish in relationship of tablet intensity and dissolution rate. Desai
et al. documented the reduced dissolution stability of HCTZ
formulation containing sodium starch glycorate without which the
dissolution would be unacted [57].
Determination of λmax of pure HCTZ:
The pure form of HCTZ was accurately weighed 10 mg dissolved
in acetone and made up to the mark with distilled water in 100 mL of
volumetric flask. The stock solution was further diluted suitably with
water to give a concentration of 10 g/mL and scan on spectrophotometer
with data processing system. Maximum absorbance is obtained at 270
nm (Fig. 5.3).
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 141
Fig. 5.3: Determination of λmax of pure HCTZ
Verification of Beer’s Lambert law:
Aliquots of the standard solution of pure HCTZ was pipetted out
into 10 mL volumetric flask .The volume was made up to the mark
with water, to obtain a concentration of 0.2-25 µg /mL.
The absorbance of prepared solutions of HCTZ was measured at
270 nm using against appropriate blank. Averages of such eleven sets
of values were taken for standard calibration curve. Beer’s law obeyed
in concentration range of 0.4 – 25 g/mL.
Fig. 5.4: Verification of Beer’s Lambert law
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 142
Solubility measurements:
The solubility of HCTZ in different concentrations of surfactants
was determined by placing 75 mg of HCTZ in 25 mL of media and
gently agitated on a magnetic stirrer for 40 minutes at 37°C ± 0.5°C.
Supernatant was filtered through 0.45 μm syringe filter. 0.1 mL
sample was withdrew and diluted with distilled water up to the mark
in 25 mL volumetric flask and then analyzed at 270 nm by UV-visible
spectrophotometer. The mean results of triplicate measurements were
recorded.
Table 5.2: Solubility of HCTZ in different media
S. No.
Sample
Wt. of
drug (mg)
Overall volume
(mL)
Abs.
Solubility increase in fold
1. HCTZ + Distilled water 75 25 0.067 1.00
2. HCTZ + CTAB 75 25 0.075 1.12
3. HCTZ + PVP 44000 75 25 0.089 1.33
4. HCTZ + PEG 400/CTAB 75 25 0.095 1.41
5. HCTZ + SLS 75 25 0.080 1.20
6. HCTZ + PEG 4000/PVP 4000 75 25 0.081 1.21
6. HCTZ + PEG 4000 75 25 0.078 1.17
7. HCTZ + PEG 400 75 25 0.305 4.46
Fig. 5.5: Solubility determination of KTCZ in different fluids
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 143
In Vitro dissolution study:
1. Apparatus: Electrolab TDT – 08L USP apparatus.
2. Dissolution Media: 0.000125 M PEG 400.
3. Rotation speed: 100 rpm.
4. Preparation of HCTZ standard solution: 1.4 mg HCTZ USP
standard was weighed precisely, put in 100 mL volumetric flask
and made up to the mark with dissolution media.
5. Test preparation: Dissolution testing was performed on tablets
containing 12.5 mg HCTZ in 0.000125 M PEG 400 (37°C ± 0.5°C)
using paddle method. Sample of 5 mL were withdrawn at regular
time intervals, replaced by fresh medium and spectro-photometrically
analyzed at 270 nm after filtration through 0.45 m syringe filter.
All dissolution tests were performed in triplicate.
6. Time point: Dissolution amount was measured separately at 10,
20, 30, 40, 50, 60 and 70 minutes.
claim Lable
100
100
potency
dilution Test
dilution Std.
Std. of Absorbance
Sample of Absorbance
Table 5.3: Sample absorbance at different time intervals
S. No. Time (min) Absorbance
H1 H2 H3
1. 10 0.082 0.057 0.061
2. 20 0.099 0.079 0.074
3. 30 0.145 0.129 0.173
4. 40 0.234 0.221 0.216
5. 50 0.245 0.245 0.225
6. 60 0.256 0.267 0.235
7. 70 0.27 0.287 0.267
Standard Abs. 0.301
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 144
Table 5.4: % drug release of various formulations in polyethylene glycol 400 at different time
S. No. Time (min) % drug release
H1 H2 H3
1. 10 27.46 19.08 20.42
2. 20 33.48 26.45 24.78
3. 30 48.55 43.2 57.34
4. 40 78.36 74 72.33
5. 50 82.04 82.04 75.34
6. 60 85.73 89.41 78.61
7. 70 90.41 96.11 89.41
Table 5.5: log time, square root of time and log % of drug release
S. No.
Time (min)
log time
Square root of time
log % drug release
H1 H2 H3
1. 10 1.0 3.16 1.43 1.28 1.31
2. 20 1.30 4.47 1.52 1.42 1.39
3. 30 1.47 5.47 1.68 1.63 1.75
4. 40 1.60 6.32 1.89 1.86 1.85
5. 50 1.69 7.07 1.91 1.91 1.87
6. 60 1.77 7.74 1.93 1.95 1.89
7. 70 1.84 8.36 1.95 1.98 1.95
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 145
Fig. 5.6: Dissolution profile (n=3) of three commercial products of HCTZ in polymeric micellar media (Zero order plot)
Fig. 5.7: Regression plot for zero order
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 146
Fig. 5.8: First order plot
Fig.5.9: Regression plot for first order
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 147
Fig. 5.10: Korsmeyer Plot
Fig. 5.11: Regression plot Korsmeyer model
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 148
Fig. 5.12: Higuchi Plot
Fig. 5.13: Regression plot for Higuchi model
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 149
Table 5.6: Kinetic parameters for H1
S. No. Time
(min)
Rate Constant (k)
First order Korsmeyer Higuchi Zero order
1. 10 23.0 × 10-2 6.14 × 10-2 - -
2. 20 11.8 × 10-2 4.63 × 10-2 1.34 0.30
3. 30 8.5 × 10-2 5.06 × 10-2 3.85 0.70
4. 40 9.5 × 10-2 6.69× 10-2 8.04 1.27
5. 50 8.9 × 10-2 6.00 × 10-2 7.71 1.09
6. 60 10.3 × 10-2 5.53 × 10-2 7.52 0.97
7. 70 - 5.24 × 10-2 7.52 0.89
r2 0.8789 0.9338 0.9285 0.9277
Slope (n) 0.69
Table 5.7: Kinetic parameters for H2
S. No. Time
(min)
Rate Constant (k)
First order Korsmeyer Higuchi Zero order
1. 10 0.230 2.38 × 10-2 - -
2. 20 0.117 1.75 × 10-2 1.64 0.36
3. 30 0.084 1.97 × 10-2 4.40 0.80
4. 40 0.080 2.57 × 10-2 8.68 1.37
5. 50 0.075 2.32 × 10-2 8.90 1.25
6. 60 0.087 2.15 × 10-2 9.07 1.17
7. 70 - 2.00 × 10-2 9.20 1.10
r2 0.8984 0.9571 0.9537 0.9636
Slope (n) 0.92
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 150
Table 5.8: Kinetic parameters for H3
S. No. Time
(min)
Rate Constant (k)
First order Korsmeyer Higuchi Zero order
1. 10 0.230 3.34 × 10-2 - -
2. 20 0.1169 2.27 × 10-2 0.97 0.21
3. 30 0.0937 3.75 × 10-2 6.74 1.23
4. 40 0.0858 3.73 × 10-2 8.20 1.29
5. 50 0.0737 3.22 × 10-2 7.76 1.09
6. 60 0.0682 2.89 × 10-2 7.51 0.96
7. 70 - 2.89 × 10-2 8.24 0.98
r2 0.8196 0.9145 0.9307 0.9257
Slope (n) 0.83
RESULTS AND DISCUSSION
It is well known that the nature of the drug formulation can also
influence the dissolution process. To investigate this effect, solubility
of HCTZ at different concentration of surfactants was studied. This
was based on the assumption that polymer dissolution during the
time course of study changes the surface tension of the medium and
increase drug solubility. A significant increase in solubility was
observed in the concentration ranges studied (Table 5.2). This can be
attributed to the surface activity of the polymeric surfactant. The
surface tension of water (at 20°C) is 72 mN/m and that of PEG 400 at
the same temperature is 60.25 mN/m. This reduction in surface
tension can increase the wetting of the drug particles and as a result,
increase the solubility.
Dissolution of HCTZ from all the tablets was studied in PEG-
400. This dissolution media is selected on the basis of solubility
measurements. Different kinetic models were applied for study of
release rate.
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 151
Dissolution of HCTZ from all the tablets followed Korsmeyer
model. Plot of log percent release vs log time was found to be linear (r2
in the range 0.91-0.95). From the slopes of linear plots the dissolution
rates were calculated. The kinetic parameters of three brands of
tablets are summarized in table 5.6, 5.7, 5.8.
Depending on the dose size and solubility characteristics of low
solubility drugs, a meaningful and discriminatory power of
dissolution rate testing can be demonstrated.
Solubility of HCTZ increased directly with PEG 400
concentration.
For a 12.5 mg HCTZ tablet, PEG 400 at 0.000125 M level is
required for a discriminative dissolution test.
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 152
Preparation of stock solution of pure HCTZ drug:
Stock solution of HCTZ was prepared by dissolving 297 mg in
1:1 acetic acid and water (v/v) and made up to the mark in 100 mL
volumetric flask. The above stock solution was further diluted to get a
working standard solution of 1 to 50 mg/mL.
Preparation of calibration curve in presence of V(V):
Aliquot of reference standard solution of HCTZ from 0.1 – 8 mL
were pipetted in to series of 10 mL of volumetric flask. In each flask
0.125 mL of PEG 400, 0.1 mL V(V), 0.55 mL of H2SO4 were
successively added and diluted with distilled water up to the mark.
The contents of each flask were mixed well and allow standing for 10
min. The increase in absorbance at 365 nm was recorded as a
function of time against the reagent blank prepared similarly. The
amount of the drug was calculated from the calibration graph.
Fig. 5.14: Absorption maxima of V(V) and V(IV)
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 153
Table 5.9: Reaction mixture
Sample
Concentration (M)
Stock solution (M) Required (M)
[HCTZ] 0.01 1 × 10-4 – 8 × 10-3
[V(V)] 0.01 0.0001
[H+] 18 1
[PEG 400] 0.01 1.25 × 10-4
Overall volume 10 mL
Table 5.10: Absorbance of standard solutions of pure drug at
different concentrations in presence of V(V)
S. No. Concentration (M) Absorbance (at 365 nm)
1. 0.0001 0.124
2. 0.0004 0.126
3. 0.0008 0.128
4. 0.001 0.130
5. 0.002 0.133
6. 0.004 0.139
7. 0.006 0.148
8. 0.008 0.154
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 154
Fig. 5.15: Calibration curve for pure drug in presence of V(V)
Preparation of sample solutions:
Ten tablets of each commercial pharmaceutical brand to be
studied were weighted and finely powdered. A portion of this powder,
equivalent to 297 mg of HCTZ was accurately weighed. The sample
was shaken with 1:1 acetic acid and water in a magnetic stirrer for 10
minutes and filtered through 0.45 μm syringe filter paper. This
solution was then diluted with acetic acid and water (1:1) in calibrated
100 mL flask. The 0.4, 0.8 and 2.0 mL of solution was pipetted in 10
mL volumetric flask. The three solutions of HCTZ were obtained (4 ×
10-4 to 1 × 10-3 M) applying the same procedure drug solutions.
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 155
Table 5.11: Absorbance of sample solutions of different marketed brands at three concentrations
S.
No.
Concentration
(M)
Absorbance (at 365 nm)
Pure drug H1 H2 H3
1. 0.0004 0.126 0.127 0.125 0.124
2. 0.0008 0.128 0.130 0.125 0.129
3. 0.001 0.130 0.129 0.131 0.127
Table 5.12: Recovery Study
S.
No. Label claim in mg
Amount of drug found (%)
H1 H2 H3
1. 12.5 100.7 99.3 99.2
2. 12.5 101.6 100.9 101.0
3. 12.5 99.23 100.5 98.0
Average Recovery (%) 100.6 100.3 99.4
Standard Deviation 1.14 0.83 1.50
RESULTS AND DISCUSSION
Spectral studies:
The spectrum of reference pure drug of HCTZ in aqueous
solution shows one absorbance band at 270 nm. The addition of
acidic solution of V(V) to the drug solution causes change in the
absorption spectrum with new characteristic band appearing at 365
nm. HCTZ oxidizes by aqueous acidic vanadium (V). Simultaneously
V(V) was produced as reaction proceeds. The equilibrium is attained
in ~50 minute. The yellow color changes to light green and finally
becomes blue on the completion of reaction. This indicates formation
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 156
of an intermediate complex between V(V) and HCTZ. Therefore, a
kinetically based spectrophotometric method was developed for the
quantitative determination of HCTZ by measuring the increase in
absorbance at 365 nm as a function of time.
Linearity:
The linearity range was observed between from 0.029–3.18
mg/mL.
Application of the method to tablets:
The validity of the proposed method was presented by recovery
studies. For this purpose, a known amount of reference drug was
spiked to marketed tablets at three different concentration levels.
Each level was repeated five times. The results (Table 5.12) were
reproducible with low SD. No interference from the common excipients
was observed. The applicability of the proposed method for the
determination of HCTZ has been tested on commercially available
pharmaceutical formulations.
Limit of detection and quantification
The limit of detection (LOD) and quantification were evaluating
the minimum level at which the analyte could be readily detected and
quantified with accuracy, respectively. The LOD was 3.43 mg/mL and
LOQ was 11.45 mg/mL.
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 157
Table 5.13: Quality Control Parameters
S.No. Parameters HCTZ
1. max (nm) 365
2. Beer’s Range (mg/mL) 0.029 – 3.18
3. Molar Absorptivity (L mol-1 cm-1) 8.85 × 103
4. Sandell’s Sensitivity (g cm-2) 0.033
5. Regression equation 0.9898
6. Intercept 0.1253
7. Slope 0.1045
8. Limit of Detection (mg/mL) 3.28
9. Limit of Quantization (mg/mL) 10.95
10. Standard deviation of calibration line 0.114
PROPOSED MECHANISM
The equivalent concentration of reactants was taken in a
reaction vessel and the reaction was allowed to completion. The
reaction products formed were identified by the following procedure.
The formation of free radicals during the course of the reaction
was tested by polymerization of the acrylonitrile monomer. To a small
portion of the reaction mixture 1-2 mL of acrylonitrile monomer was
added and rest aside for 24 hours. Precipitation of polymerized
acrylonitrile was obtained. This confirms the possibility of the
formation of free radicals during the course of the reaction. The
confirmation of product was performed using the LC/MS analysis.
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 158
Fig. 5.16: LC/MS spectrum of standard HCTZ and HCTZ + V(V)
VO2 + 2H+ V (OH)2
3+
V (OH)2
+3+ HSO4
-V (OH)[
2 HSO4
]2+
R N V
H
H OH
OH
SO4H
Intermidiate
Intermidiate + H2OSlow
RNH + V(IV) + H3O+
RNH + HNRfast
CouplingRNH - NHR
Hydrazo derivative
RNH - NHR + 2 V(V) + H2Ofast
R-N=N-R + 2V(IV) + 4H +
Azoxy derivative
RNH2+[V(OH)2HSO4]2+
.
. .
+
2+
Where R =
[ ]
NH
NH
S
Cl
SO2
OO
(m/z 589)
HCTZ
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 159
The critical micellar concentration of PEG 400 was found to at
0.000125 M. The reaction shows that PEG and H+ both favors the
metabolic conversion of HCTZ.
HCTZ obeyed the Beer’s law from 0.029 – 3.18 mg/mL and from
liner equation slope, intercept, molar absorptivity, Sandell’s sensitivity
were also calculated (Table 5.13).
It has been reviewed by several researchers that HCTZ is
metabolized very low and except 4% of drug get excreted unchanged.
The reaction proceeded by free radical in micellar media. The
kinetic evidence shows that there is a complex formation between
substrate and oxidant. This is further confirmed by spectro-
photometrically.
As far as the oxidation of HCTZ is concerns, only few
mechanistic studies have been published. In this study oxidation of
HCTZ by V(V) in micellar medium have been proposed. During this
study it appeared that HCTZ dimers are formed (Fig. 5.16).
CONCLUSION
The proposed method was applied satisfactory to the
determination of HCTZ in pharmaceutical preparations.
The apparent molar absorptivity and Sandell’s sensitivity of the
resulting colored product were found to be 8.85 × 103 L mol-1
cm-1 – 0.033 g cm-1 respectively. The values of three parameters
can be considered satisfactory at least for the drug
concentration level examined.
Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 160
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Chapter-5 Hydrochlorothiazide
Department of Chemistry Dr. Hari Singh Gour Central University, Sagar (M.P.) 161
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