WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Muktiyar et al. World Journal of Pharmacy and Pharmaceutical Sciences

SJIF Impact Factor 6.647

Volume 6, Issue 8, 2127-2140 Research Article ISSN 2278 – 4357

FORMULATION AND EVALUATION OF QUINAPRIL SUSTAINED

RELEASE MATRIX TABLETS

Mogal Muktiyar*, M. V. Jhansipriya and Narapusetty Naidu

Department of Pharmaceutics, Bellamkonda Institute of Technology and Sciences,

Kambhalapadu (Village), Podili, Prakasam (District), India-523240.

Article Received on ABSTRACT

14 June 2017,
The present investigation was undertaken to design, formulate and
Revised on 04 July 2017,
Accepted on 25 July 2017, evaluate Quinapril matrix tablets for sustained release dosage form.
DOI: 10.20959/wjpps20178-9879
The blends of different formulations were evaluated for angle of
repose, bulk density, tapped bulk density, compressibility index and
*Corresponding Author hausner’s ratio. Quinapril sustain release matrix tablets were subjected
Mogal Muktiyar
to various evaluation studies such as average weight, weight variation,
Department of
thickness, drug content and friability. The drug content of all the tablet
Pharmaceutics,
Bellamkonda Institute of formulations lies within the acceptable range of 96.3-100.2%. In vitro
Technology and Sciences, dissolution studies of the formulations F1 to F10 of sustained release
Kambhalapadu (Village), tablets of Quinapril were carried out in 0.1N HCl & pH 6.8 phosphate
Podili, Prakasam
buffers. The dissolution profile revealed that as the viscosity polymer
(District), India-523240.
increases, release rate get decreased. It was concluded that, the high
viscous polymers better retard the release rate when compared to usage of low viscous
polymers. From the compatability studies it was concluded that there was no interaction
between the polymers and drug.

KEYWORDS: Quinapril, Sustained release dosage form, Matrix tablets.

1. INTRODUCTION
DEFINITION OF SUSTAINED RELEASE[1-3]
Sustained release, sustained action, prolonged action controlled release, extended action,
timed release, depot and repository dosage forms are terms used to identify drug delivery
systems that are designed to achieve a prolonged therapeutic effect by continuously releasing
medication over an extended period of time, after administration of a single dose.

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SRF’S describes the slow release of a drug substance from a dosage form to maintain
therapeutic response for extended period (8-12hr) of time. Time depends on dosage form in
oral form it is in hours, and in parenteral’s it is in days and months.[4-8]

Fig.No.1.1: Plasma Drug profile-time curve of different dosage forms

An advantage of SRF’s[9-10]
 Improved patient compliance
 Less frequent dosing
 Allows whole day coverage.

 Decreased local and systemic side effects

 Decreased GIT irritation
 Decreased local inflammation.

 Better drug utilisation

 Decreased total amount of drug used.
 Minimal drug accumulation on chronic dosing.

 Improved efficiency in treatment

 Uniform blood and plasma concentration.
 Decreased fluctuation in drug level i.e. uniform pharmacological response.
 Increased bioavailability of some drugs.
 Special effects: SR aspirin gives symptomatic relief in arthritis after waking.

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 Economy
Sustained Release Systems[11-13]
The sustained release systems can be broadly classified into 6 types which are further
subdivided as given below.

Diffusion controlled
 Reservoir.
 Matrix.
 Reservoir and monolithic.

Dissolution controlled
 Encapsulation.
 Matrix.

Water penetration controlled

 Osmotically controlled.
 Swelling controlled.

Chemically controlled
 Erodible systems.
 Drug covalently linked with polymer.

Hydrogels
 Chemically controlled.
 Swelling controlled.
 Diffusion controlled.
 Environment responsive.

Ion-exchange resins
 Cationic exchange.
 Anionic exchange.

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2. MATERIALS AND METHODS

2.1. MATERIALS USED
Quinapril, Micro Crystalline Cellulose (MCC), Hydroxy Propyl Methyl Cellulose (HPMC),
Carbomer, Chitosan, Xanthum Gum, Talc, Magnesium stearate.

2.2. METHODS USED

2.2.1. PREPARATION OF QUINAPRIL SUSTAINED RELEASE TABLETS BY
DIRECT COMPRESSION METHOD
Compressed tablets of Quinapril using different polymers were prepared by direct
compression method, as per given Official formulae. Accurately weighed quantities of drug,
polymer was passed through sieve no #40 and remaining ingredients were added to the blend
in a polybag and mixed well for 10 minutes. Sufficient quantities of Micro crystalline
cellulose is used to raise the total bulk of the tablets to a weight of 100mg each. The resulting
powder blend was compressed on single punch tablet press (Cadmach, India) using 8 mm
round punches to the hardness of 6-8 kg/cm2.

2.2.2. PRE COMPRESSIONAL PARAMETERS OF SUSTAINED RELEASE

TABLETS BLEND
Bulk density; Apparent bulk density was determined by pouring the blend into a graduated
cylinder. The bulk volume (Vb) and weight of the powder was determined.[14]
Bulk density = M / Vb

Tapped density
The measuring cylinder containing a known mass of powder blend was tapped for a fixed
number of times as per USP apparatus-11. The minimum volume occupied by the powder
after tapping was measured.[15]
Tapped density = weight/tapped volume

Compressibility index: Compressibility index is calculated as follows

Tapped density- Bulk density/ Tapped density*100

The value below 15% indicates a powder with good flow characteristics where as above 25%
indicates poor flowability.

Haussner’s ratio: It is an indirect index of ease of powder flow, it is calculated as follows.

Tapped density/Bulk density

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Haussner’s ratio <1.25 indicates good flow properties, where as >1.5 indicates poor
flowability.[16]

Angle of Repose
Angle of repose was determined using funnel method. The blend was poured through funnel
that can rise vertically until a maximum cone height (h) was obtained. Radius of the heap(r)
was measured and angle of repose was calculated as follows.[17]
Ø= h/r tan-1 h/r

2.2.3. POST COMPRESSIONAL PARAMETERS OF SUSTAINED RELEASE

TABLETS BLEND
Average Weight
20 Tablets were weighed and calculated based upon the formula.

Hardness test
The force required to break a tablet in a diametric compression was determined by using
Pfizer tablet hardness tester.[18]

Friability
The weight of twenty tablets was noted and placed in the friabilator and then subjected to100
revolutions at 25 rpm. Tablets were dedusted using a soft muslin cloth and reweighed.[19]
Percent friability = [initial weight – final weight / initial weight] × 100

Weight variation
Twenty tablets from each formulation were selected randomly and average weight was
determined. Individual tablets were then weighed and compared with average weight.[20]

Drug content uniformity[18-20]

The drug content uniformity was determined by taking the powder equivalent to 10mg, then
it was (n=3) dissolved in PH6.8 phosphate. Required dilution (10µg/ml) was prepared and
absorbance was taken against the blank at 246nm.

Dissolution studies[18-20]
The tablet samples were subjected to In-vitro dissolution studies using USP Type II
dissolution apparatus at 37±0.5°C and 50rpm speed. To mimic the Gastrointestinal
conditions, as per the official recommendation of USFDA, 900 ml of 0.1 N HCL was used as

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dissolution medium for initial 2hr and 6.8Ph buffer for next 10 hr. Aliquot equal to 5mL was
withdrawn at specific time intervals and replaced with fresh buffer. The aliquots were diluted
and drug release was determined spectrophotometrically at a wavelength of 246 nm by
comparing with the standard calibration curve.

FTIR studies
The drug- excipients interaction was studied using FTIR. IR spectra for drug and powdered
tablets were recorded in a Fourier transform infrared spectrophotometer using KBr pellet
technique. This spectra was scanned over the 3600 to 500 cm-1 range.

3. RESULTS and DISCUSSION

Table-1: Formulation design of Sustain release tablets of Quinapril.
Ingradients
F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
(In mgs)
Quinapril 20 20 20 20 20 20 20 20 20 20
HPMC K4M 10 15 - - - - - - - -
HPMC E15M - - 10 15 - - - - - -
HPMC E100M - - - - 10 15 - - - -
Carbomer - - - - - - 10 15 - -
Chitosan - - - - - - - - 10 15
Xanthun Gum 20 15 20 15 20 15 20 15 20 15
Microcrystalline cellulose 45 45 45 45 45 45 45 45 45 45
Megnesium sterate 3 3 3 3 3 3 3 3 3 3
Talc 2 2 2 2 2 2 2 2 2 2
Total Weight 100 100 100 100 100 100 100 100 100 100

Table-2: Powder flow properties for all the formulations.

Powder Angle of Bulk density(ρb) Tapped density(ρt) Compressibility Hausner’s
Blend Repose (θ) (g/mL) (g/mL) index (%) ratio
F1 22° 41± 0.5 0.31±0.05 0.45±0.04 29.06± 0.04 1.22±0.05
F2 32° 21±0.39 0.35±0.03 0.40±0.05 18.57± 0.05 1.14±0.06
F3 31° 21±0.69 0.30±0.05 0.41±0.02 19.02± 0.03 1.18±0.06
F4 25° 11±0.22 0.31±0.01 0.40±0.08 21.03± 0.02 1.16±0.02
F5 21° 43±0.18 0.33±0.02 0.42±0.02 20.06± 0.01 1.17±0.03
F6 23° 51±0.32 0.30±0.01 0.41±0.04 22.04± 0.04 1.19±0.03
F7 22° 01±0.29 0.35±0.03 0.42±0.04 27.05± 0.01 1.14±0.04
F8 28° 21±0.12 0.31±0.00 0.40±0.03 23.03± 0.03 1.13±0.02
F9 24° 11’±0.19 0.32±0.01 0.43±0.01 25.04± 0.02 1.12±0.02
F10 26° 21±0.12 0.35±0.03 0.42±0.02 23.03± 0.04 1.14±0.05

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Table 3: Quality Control Tests For The Sustained Release Tablets of Quinapril.
Average weight Thickness Hardness Friability Weight variation Drug content
Formulations
(mg) (mm) Kg/cm2 (%) (±sd) (%)
F1 98 2.38 6.8 0.2 98±0.66 98.5
F2 99 2.51 6.9 0.4 99±0.02 99.6
F3 99 2.47 7 0.5 99±0.02 98.3
F4 98 2.53 7.1 0.2 98±0.03 100.8
F5 96 2.62 7.2 0.2 96±0.03 100.2
F6 101 2.28 6.8 0.4 100±0.03 98.7
F7 96 2.37 6.7 0.1 97±0.03 98.6
F8 99 2.46 7.1 0.3 99±0.03 100.2
F9 98 2.49 7.2 0.4 98±0.04 98.5
F10 99 2.60 6.9 0.1 99±0.04 99.9

Table-4: Dissolution profile for Quinapril from formulations F1 to F10.

Time in
F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
(Hours)
0 0 0 0 0 0 0 0 0 0 0
1 12.35 10.49 15.98 12.23 13.25 11.26 17.82 8.92 14.28 8.25
2 19.46 18.58 28.64 19.42 20.17 18.39 26.77 15.67 21.96 14.29
3 25.53 23.47 39.37 25.21 31.58 29.37 34.84 20.39 33.57 21.37
4 39.23 38.76 50.21 32.15 42.89 37.12 43.76 30.21 40.29 29.18
6 63.12 59.25 69.14 55.36 61.21 59.17 60.28 42.14 64.27 41.51
8 73.45 70.26 83.26 76.89 79.26 72.26 75.26 60.96 79.78 60.38
10 87.86 85.35 98.78 89.17 90.38 88.39 88.34 70.24 91.35 70.27
12 98.37 97.36 - 99.39 99.23 98.37 97.34 88.36 98.34 88.31

Figure-1: Comparative Dissolution profile of Quinapril from formulations F1 to F5.

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Figure-2: Dissolution profile for Quinapril from formulations F6 to F10.

Table-5: Coefficient Of Correlation (R2) values of different batches of Quinapril

sustained release tablets.
Release model
Formulation code
First order Zero order Koresmeyer-peppas Higuchi Matrix
F1 0.985 0.953 0.960 0.989
F2 0.945 0.911 0964 0.969
F3 0.984 0.953 0.964 0.992
F4 0.998 0.994 0.996 0.998
F5 0.986 0.982 0.996 0.911
F6 0.996 0.992 0.998 0.952
F7 0.973 0.772 0.993 0.991
F8 0.960 0.937 0.993 0.995
F9 0.965 0.932 0.906 0.986
F10 0.986 0.976 0.902 0.920

Figure-3: Higuchi plots for the formulations F1 to F10.

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Fig-4: FT-IR spectra of Quinapril.

Fig-5: FT-IR Spectra of Quinapril+ HPMC.

Fig-6: FT-IR spectra of Quinapril + Carbomer.

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Fig-7: FT-IR spectra of Quinapril+ Chitosan.

Fig-8: FT-IR spectra of Quinapril+ Xanthum gum.

Fig-9: FT-IR spectra of optimized formulation F8.

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Fig-10: FT-IR spectra of Optimized formulation F10.

Table 6: Stability studies for formulation F8.

STABILITY PERIOD % DRUG CONTENT % DRUG RELEASE
INITIAL 100.2 99.57
FIRST MONTH 100.1 99.18
SECOND MONTH 99.7 98.91
THIRD MONTH 99.6 98.87

Table 7: Stability studies for formulation F10.

STABILITY PERIOD % DRUG CONTENT % DRUG RELEASE
INITIAL 99.2 99.64
FIRST MONTH 99.1 99.24
SECOND MONTH 89.8 98.89
THIRD MONTH 89.7 98.56

4. SUMMARY AND CONCLUSION

Sustained release formulations for Quinapril tablets were developed with a view to reduce the
frequency of administration and to improve patient compliance. The influence of different
grades of HPMC and rate retarding materials were studied. The release rate of Quinapril was
found to be influenced by the nature and concentration of rate retarding materials. The release
can be retarded by high viscosity grades.

The following conclusions were drawn from the present investigation.

 The present study resulted that the development of Quinapril sustained release tablets by
direct compression technique.

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 Pre-formulation studies indicated that the drug and polymer were found to be compatible
with each other.
 The release rate was dependent upon method of compression, direct compressible tablets
yielded slow release.
 The release rate of drug was dependent upon the nature and concentration of polymer
employed.
 The release rate was found to be reduced with the incorporation of high viscous grades of
rate retarding materials.
 All the formulated tablets followed first order release kinetics and controlled by Higuchi
mechanism of diffusion.
 The release rate of Quinapril from the matrix tablets was found to be dependent on
concentration of Xanthum gum and chitosan.
 The rate retarding materials were used in the Concentration Of 20% release the drug
slowly when compared with the hydrophilic materials like HPMC

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