Research J. Pharm. and Tech.

14(6): June 2021

ISSN 0974-3618 (Print) www.rjptonline.org

0974-360X (Online)

RESEARCH ARTICLE

Formulation and Evaluation of Mouth Dissolving Tablet of Benazepril

Hydrochloride
Vani H. Bhargava1, Poonam S. Sable2*, Deepak A. Kulkarni2, Geeta P. Darekar2
1
Smriti College of Pharmaceutical Education, Indore, 452010, Madhya Pradesh, India.
2
Srinath College of Pharmacy, Aurangabad, 431136, M.S. India.
*Corresponding Author E-mail: pnmshrsat@gmail.com
ABSTRACT:
Antihypertensive drugs are expected to give quicker action with better bioavailability. In the present study,
mouth dissolving tablets of Benazepril Hydrochloride were formulated by using direct compression technique
employing combination of a superdisintegrants to achieve rapid disintegration of the tablets in oral cavity
Croscarmellose sodium, sodium starch glycolate and crospovidone were used as superdisintegrant to prepare six
batches of mouth dissolving tablets out of which tablets prepared from crospovidone showed best results. Drug
and physical mixture was characterized by FTIR for compatibility study. Optimization technique was employed
to predict the best formulation of all the combinations prepared. Prepared formulations were optimized and
evaluated for wetting time, dispersion time and different quality parameters. Optimized formulation was
compared with marketed formulation for in vitro drug release and it was found that mouth dissolving tablet
shows efficient drug release.

KEYWORDS: Benazepril Hydrochloride, Mouth dissolving, Tablet, Drug release, Antihypertensive.

INTRODUCTION:
Benazepril Hydrochloride (Fig. 1) is the ACE
(Angiotensin Converting Enzyme) inhibitor. ACE
(Angiotensin Converting Enzyme) inhibitors are used
largely in the treatment of hypertension and congestive
heart failure1. Dilation of blood vessels is the major
mechanism which results in lowering of blood pressure.
ACE inhibitors are also prescribed for cardiac failure,
diabetic nephropathy, chronic renal failure, renal
involvement in systemic sclerosis (scleroderma renal
crisis), left ventricular systolic dysfunction, and acute
myocardial infarction2. Fig. 1: Chemical structure of Benazepril Hydrochloride.

Efficiency, quicker onset and longer duration of action

are the advantages of Benazepril Hydrochloride at the
same time low bioavailability is the limitation so by
incorporating this drug in mouth dissolving tablet,
bioavailability can be improved3. Mouth Dissolving
Tablets (MDTs) rapidly disintegrates when placed on the
tongue. Orally disintegrating tablets have better patient
acceptance and compliance and may offer improved
biopharmaceutical properties, efficacy and increased
Received on 21.04.2020 Modified on 16.07.2020 bioavailability compared with conventional oral dosage
Accepted on 20.08.2020 © RJPT All right reserved forms4. Major intention behind MDT products initially
Research J. Pharm. and Tech. 2021; 14(6):3161-3166. was to overcome the difficulty in swallowing of
DOI: 10.52711/0974-360X.2021.00551
conventional tablets and capsules among pediatric and
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geriatric populations5. Former applications of MDTs are drug was prepared by simple blending. The IR spectra
significant in the management of many conditions such for drug and physical mixture with drug were obtained
as allergies, cold, and flu symptoms. High porosity in the using FT-IR instrument. IR spectrum were observed for
tablet matrix is the key factor for rapid disintegration of detection, insertion or shifting of peaks8.
MDT. To improve the porosity, volatile substances such
as subliming agents can be used in tableting process, Formulation of Tablets:
which sublimated from the formed tablet. Also freeze- The raw materials were passed through a no. 100 screen
drying technique is used to form a highly porous MDT 6. prior to mixing. Benazepril hydrochloride,
Direct compression using superdisintegrant is the superdisintegrant, microcrystalline cellulose and
conventional technique that can be used for preparation mannitol were mixed using a glass mortar and pestle.
of MDT. MDTs prepared by direct compression shows The blends were lubricated with magnesium stearate.
better disintegration due to absence of binder and low The blends ready for compression were converted into
moisture contents. Generally recommended tablets using a 16 station-punch tablet machine. Before
concentration of superdisintegrants generally used is 1- compression final blend were evaluated for mass-volume
10% by weight relative to total weight dosage form. relationship (bulk density, tapped density, Hausner’
Crosscarmellose sodium (Ac-Di-Sol), Sodium Starch ratio, compressibility index) and flow properties (Angle
Glycolate (SSG) and Crosspovidone (CP) are the of repose). To know the actual amount of three
generally used superdisintegrants7. superdisintegrant for the desirable property of fast
dissolving tablets a 32 randomized full factorial design
MATERIAL AND METHODS: was used. In this design one factor was evaluated, each
Chemicals and reagents: at two levels and experimental trials were performed at
Benazepril Hydrochloride was procured from Amneal all six possible combinations (Table 1). The amount of
India Pvt. Ltd., Ahmedabad. Ac-Di-Sol (Croscarmellose Sodium starch glycolate (SSG), croscarmellose sodium
Sodium), Kollidon CL (Crospovidone) were procured and crospovidone was selected as independent
from Wings Biotech Pvt. Ltd., Baddi. Glycolys (Sodium variables9.
Starch Glycolate), Avicel PH-102 (Microcrystalline
Cellulose), Pearlitol 200 SD (Mannitol) and Magnesium Evaluation of Tablets:
stearate were procured from Signet Chemicals, Mumbai. After compression of powder blends, the prepared tablets
were evaluated for organoleptic characteristics like
Instrumentation: color, odor, taste, diameter, thickness and physical
The proposed work was carried out using instruments, characteristics like hardness, friability, disintegration
Shimadzu UV-visible spectrophotometer (model UV- time, wetting time, dispersion time10.
1800 series), FT-IR Spectroscopy (ABB FTLA 2000,
INDIA), 16 station tablet punching machine (Rimex Weight variation:
minipress-1) and USP XXIV Paddle dissolution To perform weight variation test twenty tablets were
apparatus (VDA-6DR Veego) taken and weighed individually. Individual tablet weigh
was compared with average weight of twenty tablets11.
Drug excipient compatibility by Fourier Transform
Infrared (FTIR) study: Hardness:
The FT-IR for pure drug was obtained by powder diffuse Hardness of a tablet is defined as the force applied across
reflectance on FTIR spectrometer in the wave number the diameter of the tablet in order to break the tablet.
region of 4000-400 cm-1. The spectrum was compared Hardness of the tablet of each formulation was
with the reference spectrum of Benazepril determined using Monsanto Hardness Tester12.
Hydrochloride. The physical mixture of excipient with

Table1: Formulation of Factorial Design Batches of MDTs

Ingredients (in mg) MDT1 MDT2 MDT3 MDT4 MDT5 MDT6
Benazepril Hydrochloride 10 10 10 10 10 10
Crospovidone 30 45 - - - -
Sodium Starch Glycolate - - 30 45 - -
Croscarmellose Sodium - - - - 30 45
Avicel PH 102(Microcrystalline cellulose) 50 50 50 50 50 50
Magnesium Stearate 6 6 6 6 6 6
Mannitol 154 139 154 139 154 139

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Friability: spectrum of drug sample was concordant with reference

Friability of the tablets was determined using Roche spectra. The FT-IR spectra verified the authenticity of
friabilator. This device subjects the tablets to the the procured sample as the characteristic peaks of the
combined effect of abrasions and shock in a plastic drug were found at 3435 (O–H stretching), 2980 (N–H
chamber revolving at 25rpm and dropping the tablets at a
stretching), 2467 (C–N stretching), 1739 (Acid C=O
height of 6 inch in each revolution. Preweighed sample stretching) and 1674 (C=C stretching). Drug-excipient
of tablets was placed in the friabilator and were interaction study was carried out for 4 weeks and
subjected to 100 revolutions. Tablets were dedusted samples were evaluated after every week for physical
using a soft muslin cloth and reweighed. changes, change in absorption maxima and by FT-IR
spectra. There was not any sign of physical change at the
The friability (F%) was determined by the formula end of study. The FT-IR spectra of the physical mixture
retained all the peaks of the pure drug and there was no
F%= W0-W/W0 x 100 significant shift in the peaks corresponding to the
Benazepril Hydrochloride was observed on storage (Fig.
Where, W0 was initial weight of the tablets before the 2). Both the drug and excipient were found to be
test and W was the weight of the tablets after test13. compatible with each other. Hence, the selected drug and
excipients were successfully incorporated in the design
Wetting time: fast dissolving tablets19.
Wetting time of the tablets was measured using a piece
of tissue paper (12cm X 10.75cm) folded twice, placed
in a small petridish (ID = 6.5cm) containing 6ml of
Sorenson’s buffer (pH 6.8). A tablet was put on the
paper and the time for the complete wetting was
measured14.

In vitro dispersion time:

In vitro dispersion time was measured by placing a tablet
in a beaker which contains 10ml of 6.8pH phosphate
buffer. Three tablets from each formulation were
randomly selected and in vitro dispersion time was
performed16.
A
Optimization of Mouth Dissolving Tablet:
The optimized Mouth Dissolving tablet was prepared
with the best amount of co-processed superdisintegrant
suggested by the Design expert software. The prepared
tablets were evaluated for its physicochemical
properties17.

In vitro dissolution study:

In vitro dissolution study for optimized tablet was
carried out using USP paddle method at 50rpm in 900ml
of Sorenson’s buffer (pH 6.8) as dissolution media,
maintained at 37±0.5°C. 5ml of aliquot was withdrawn
at the specified time intervals (1 minute), filtered
B
through Whatmann filter paper and assayed Fig.2: FTIR Spectra of A) Benazepril Hydrochloride B) Benazepril
spectrophotometrically at 240nm. An equal volume of Hydrochloride + Crospovidone
fresh medium, pre-warmed at 37°C, was replaced into
the dissolution media after each sampling to maintainPrecompression parameters of tablet blend:
constant volume throughout the study18. For tablets prepared using super disintegrants, the bulk
density of blend varied between 0.688-0.742g/cc. The
RESULTS AND DISCUSSIONS: tapped density was found in the range of 0.720-0.815
Drug excipient compatibility by Fourier Transform g/cc. By using these two density data, Hausner’s ratio
Infrared (FTIR) study: and compressibility index was calculated. The powder
When Benazepril Hydrochloride compared with the blends of all formulation had Hausner’s ratio of less than
standard, it was found that drug was pure. The FT-IR 1.25 indicating good flow characteristics. Blends having

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value of compressibility index less than 16% were dispersion time and wetting time). All the formulations
considered as free flowing ones. The values for were white in color, flat in shape with smooth surface
compressibility index were found in the range of 5.555- not having any defects. The average weights of the
7.365. The flowability of the powder was also evidenced prepared tablets were found between 242.5-249.6 mg. So
by the angle of repose. The angle of repose below 30 0 it was predicted that all the tablets exhibited uniform
indicates well to excellent flow properties of powder. weight with low standard deviation values within the
Lower the friction occurring within the mass, better the acceptable variation. The friability of the formulations
flow rate. The angle of repose was found to be in the was less than 1.0%, showed the durability of the tablets;
range 23.30-27.290. The results for characterization of resistance to loss of weight indicates the tablet’s ability
blend were shown in Table 220. to withstand abrasion in handling, packaging and
shipment. The friability of all the formulations was
Post –compression Characterization of Mouth found to be less than 1.0%. It was clear from the study
Dissolving Tablets: that the concentration of super disintegrants also affected
After compression of powder, the tablets obtained were the percent friability21. The hardness of tablets varied
evaluated for their organoleptic (color, odor), physical from 3.0-3.6 kg/cm2(Table 3)
(size, shape and texture) and quality control parameters
(thickness, hardness, friability, disintegration time,

Table 2: Precompression parameters of Tablets Blends of MDTs

Formulation Parameters
Codes Bulk Density Tapped Density Hausner’s Ratio Compressibility Angle of Repose (0)
(g/cc) (g/cc) Index (%)
MDT1 0.714 ±0.010 0.765 ±0.011 1.071±0.012 6.6 ±1.123 23.30±0.867
MDT 2 0.739 ±0.012 0.796 ±0.009 1.077 ±0.023 7.16 ±1.243 25.15 ±1.232
MDT 3 0.704 ±0.019 0.745 ±0.020 1.058 ±0.031 5.555 ±1.433 24.40 ±0.934
MDT 4 0.757 ±0.006 0.815 ±0.003 1.076 ±0.011 7.111 ±1.348 26.52±1.244
MDT 5 0.688 ±0.023 0.720 ±0.013 1.046 ±0.002 4.444 ±1.298 23.50±1.423
MDT 6 0.742 ±0.034 0.801 ±0.005 1.079 ±0.022 7.365 ±1.344 27.29±1.364

Table 3: Postcompression parameters of different batches of MDTs

Formulation Parameters
codes Weight(mg) Hardness (kg/cm2) Friability (%) Wetting time (s) Dispersion time (s)
MDT1 249.6 ±1.31 3.0 ±0.08 0.42 ±0.02 11 ±1.76 16 ±1.22
MDT 2 247.5 ±1.50 3.3±0.15 0.73 ±0.05 14 ±2.35 20 ±3.24
MDT 3 248.4 ±2.05 3.2 ±0.13 0.84±0.03 13 ±4.23 18 ±2.56
MDT 4 246.2 ±1.42 3.1±0.17 0.68±0.07 15 ±4.25 21 ±4.35
MDT 5 245.5 ±1.38 3.6 ±0.16 0.83 ±0.04 19 ±3.41 26 ±3.75
MDT 6 242.5 ±2.52 3.5± 0.19 0.35 ±0.06 22 ±3.54 30 ±2.47
n=3, ±SD

Super disintegrants were incorporated in the

formulations (MDT1- MDT6) to facilitate quicker
disintegration of the tablet as soon as it contacts the
saliva in the mouth. These disintegrants act by drawing
water into the tablet owing to the wicking or capillary
action leading to swelling and breakup of the tablet. In
the formulation of fast dissolving tablets three super
disintegrants (sodium starch glycolate, Ac-Di-Sol and
Crospovidone) were tested in different concentrations.
The disintegration process of the tablet was fully
dependable on nature and concentration of super
disintegrant used. The in vitro wetting time was also
studied to know the time required for complete wetting
of tablets when placed on tongue22. The in vitro wetting Fig.3: In vitro wetting time of mouth dissolving tablet
time of all the formulations varied between 11±1.76 to
The same sequence was observed in case of
22±3.54 s (Fig. 3).
measurement of dispersion time of the tablet (Table 3).
The tablets with crospovidone showed the best results
for all the characterization parameters and hence it was
selected as one factor of the optimization of the fast
dissolving tablets23.
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Optimization of Mouth Dissolving Tablet:

For optimization of mouth dissolving tablets and to
know the desirable property randomized full factorial
design was used. In this design one factor was evaluated,
each at two levels and experimental trials were
performed at all six possible combinations. The
formulations and evaluation optimized batch of tablet is
shown in Table 424.

Table 4: Formulation and evaluation of optimized batch of MDT

Formulation
Ingredients Quantity (in mg)
Benazepril Hydrochloride 10
Crosspovidone 30
Avicel PH 102(Microcrystalline cellulose) 50
Magnesium Stearate 6 Fig.4: Comparative in vitro drug release of MDT and Marketed
Mannitol 154 tablet
Evaluation
Weight (mg) 249.6 ±1.31 Fig.4 shows comparative drug release of MDT and
Hardness (kg/cm2) 3.0 ±0.08 marketed tablet. From the graph it is predictable that
Friability (%) 0.42 ±0.02
Wetting time (s) 11 ±1.76
MDT have quicker onset of action with significant drug
Dispersion time (s) 16 ±1.22 release which will be helpful in patients with severe
n=3, ±SD hypertension and cardiovascular diseases.

In vitro dissolution study: CONCLUSION:

In vitro drug release study was performed at 37±0.50C in Mouth dissolving tablets of Benazepril Hydrochloride
paddle dissolution apparatus for the optimized was prepared successfully by direct compression
formulation and conventional marketed tablet. The technique using superdisintegrants. The mouth
optimized formulation showed the better release than the dissolving tablets of antihypertensive drug were found to
marketed preparation for immediate release of drug be a better option in treatment of hypertension conditions
(Table 5). MDT of Benazepril Hydrochloride showed by providing fast onset of action and thus leading to
98.68% drug release at in 10 minutes while marketed patient convenience and compliance. It is concluded that
tablet showed 98.46% drug release in 60 minutes25. by incorporating Benazepril Hydrochloride in the form
of mouth dissolving tablet, fast and better therapeutic
Table 5: Comparative % drug release of MDT with marketed action can be achieved for the treatment of hypertension.
tablet
Time (min) % Drug release
MDT1 Marketed Preparation ACKNOWLEDGEMENT:
5 91.94±2.79 - The authors are grateful to the authorities Smriti College
10 98.68±1.84 21.87±3.25 of Pharmaceutical Education, Indore, Madhya Pradesh
15 - 30.96±1.28 for the facilities.
20 - 40.41±3.54
25 - 52.92±2.74
30 - 64.80±2.38 CONFLICT OF INTEREST:
35 - 75.87±2.35 The authors declare no conflict of interest.
40 - 91.89±1.39
45 - 97.92±1.37
50 - 98.19±1.73
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