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FORMULATION AND EVALUATION OF CIPROFLOXACIN CONTROLLED RELEASE

MATRIX TABLETS INTRODUCTION

Article · January 2012

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 IJPRAS, 2012; Volume 1(4)

International Journal of Pharmaceutical

Research and Applied Science (IJPRAS)
A way to rising your innovation and dreams

ISSN 2319-7013

FORMULATION AND EVALUATION OF CIPROFLOXACIN CONTROLLED

RELEASE MATRIX TABLETS
RESEARCH ARTICLE

Sankha Bhattacharya
Department Of Pharmaceutics, Asst. Professor B.Pharmacy College Rampura,
Godhra, Gujarat

Corresponding Author Email: sankhabhatt@gmail.com

ABSTRACT:
The goal of this study was to formulate and evaluate ciprofloxacin controlled release matrix
tablets. Ciprofloxacin controlled release tablets were prepared by wet granulation method using
two polymers such as HPMC K 100M (hydrophilic polymer) and guar gum (natural polymer) The
tablet compression machine equipped with 13mm tooling of convex surface . All the Evaluation
parameters were within the acceptable limits. IR spectral analysis showed that there was no
interaction between the drug and polymers. in-vitro dissolution study was carried out using USP
dissolution test apparatus (paddle type) at100 rpm. The test was carried out at 37 ± 0.5 0 C in
900ml of the N/10 Hcl buffer as the medium for two hours, and pH 7.2 buffer from 2nd hour to
12th hour.The in vitro release study showed that if the polymer ratio is increased, then the release
of the drug is prolonged. HPMC K 100M shows a prolonged release when compared to guar gum.

Key word :Ciprofloxacin, Controlled release, HPMC K100M, Guar gum.

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 IJPRAS, 2012; Volume 1(4)

INTRODUCTION: MATERIALS :
Oral route has been the commonly adopted and most Ciprofloxacin was obtained as a Gift sample from
convenient route for the drug delivery. Tablets and Kansas Labs, HPMC K100M and Guar gum were
capsules are the major preparation before the purchased from Lamda Chemicals, Chennai . Carboxy
introduction of advanced controlled drug delivery methyl cellulose (CMC) and Starch were purchased
system Among various dosage forms, matrix tablets are from Paxmy Chemicals Mumbai. Poly vinyl pyrolidine,
widely accepted for oral controlled release as they are magnesium stearate and iso propyl alcohol were
simple to formulate and easy to make. Polymers and obtained from Apex Laboratory Chennai . All other
release retarding materials used as matrix play a vital reagents used were of analytical grade.
role in controlling the drug release from matrix tablets.
Ideal, oral CR systems are reliant upon the dosage form Preparation of ciprofloxacin Tablets
to control the rate of drug release with little or no effect The tablets were prepared by wet granulation method
from the intrinsic properties of the drug or the condition (5). Ciprofloxacin and the polymers HPMC K100M and
prevalence with in the GI tract. Realistic drug guar gum were mixed (0.5, 1.0 and 1.5) uniformly.
candidates exhibit high permeability across the GI CMC and starch was added to the drug and polymer
epithelium such that their absorption rate is controlled mixture and blended thoroughly for 5 minutes. PVP
exclusively by the rate of release from the dosage form K30 was dissolved in sufficient quantity of iso propyl
Though a variety of substances are available to serve as alcohol and was added to the drug, polymer and lactose
releasing retarding materials for matrix tablets. Natural mixture to form a coherent mass. Then the formed
gums and polysaccharides and their derivatives coherent mass was sieved manually through sieve no.
represent a group of polymers widely used in 16 to form granules. Then the granules are collected and
pharmaceutical dosage forms due to their non toxicity, dried at 400C + 20C
low cost and free availability. Natural gums and for 2 hours. The dried granules were passed through
hydrophilic polymers when in contact with water; they sieve no. 20. The granules are then subjected to
are hydrated to form a gel. Because of this property preformulation studies. After preformulation studies, the
natural gums like karaya, xanthan gum and guar gum granules were mixed with magnesium stearate
have been reported as good matrix materials for uniformly and are compressed into tablets.
controlled release tablets. bacteria the most susceptible
ones are the aerobic gram negative bacilli .The goal Table: 1 Formula of CR Tablets containing
behind the development of oral controlled release Ciprofloxacin, HPMC K 100M and Guar gum as
formulations at that time were the achievement of a polymers with three ratios (1:0.5, 1:1 and 1:1.5)
constant release rate of the entrapped drug. The aim of
the study was to formulate and evaluate ciprofloxacin Ingredient F1 F2 F3 F4 F5 F6
controlled release matrix tablets. . If the sustained (mg)
release system releases its active ingredient after Ciprofloxacin 100 100 100 100 100 100
passage through these areas, absorption of the drug may
be seriouslynimpaired. Furthermore, if the gut wall HPMC 50 100 150 - - -
and/or the first pass liver metabolism are significant, the K100M
release rate of dosage form can have strong effect on the Guar Gum - - - 50 100 150
amount of the drug that reaches the peripheral
Carboxy 10 10 10 10 10 10
circulation unchanged. Because of the above
Methyl
limitations, at present, the residence time of sustained
Cellulose
release dosage forms cannot be extended beyond 10 to
12 hours. Nevertheless, the oral route is still the most Starch 310 260 210 360 260 210
convenient and common mode of sustained release PVP K30 20 20 20 20 20 20
system. To overcome the frequent dosing of
ciprofloxacin and to provide patient compliance an Magnesium 10 10 10 10 10 10
effort was made to develop sustained release Stearate
formulations of ciprofloxacin hydrochloride 1,2,3,4,5,6. IPA Q.S Q.S Q.S Q.S Q.S Q.S

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 IJPRAS, 2012; Volume 1(4)

Evaluation of Granules Evaluation of Tablets:

Angle of repose: Hardness:

Angle of repose (θ) was determined using fixed The strength of tablet is expressed as tensile strength
funnel method. The height of the funnel was adjusted (kg/cm2). The tablet-crushing load, which is the
in such a way that the tip of the funnel just touched force, required breaking tablet by compression. It was
the apex of the heap of the granules. The granules measured using a tablet hardness tester (Pfizer
were allowed to flow through the funnel freely on to Hardness Tester).
the surface. Angle of repose was calculated using the
following equation Weight variation:
θ = tan-1 (h/r) Twenty tablets ware randomly selected and
Where h and r are the height and radius as of cone. individually weighted (shimdzu). The average weight
of tablets was calculated.
Bulk density: Friability Ten tablets were placed in the Roche
Bulk density is the ratio between a mass of granules friabilator, which was then operated for 100
and its bulk volume. It is expressed by g/cc. revolutions After 100 revolutions the tablets were
Bulk density = Weight of powder/Bulkvolume dedusted and reweighed. Percentage friability was
calculated by the following formula.
Tapped density: Percentage friability = Initial weight - Final weight ×
Tapped density is the ratio between a mass of 100.
granules and volume of the granules after tapping.
It is expressed by g/cc. Initial weight:
Tapped density = Weight of granules - Final volume Estimation of drug content Ten tablets from each
after tapping formulation were powdered. The powder equivalent
to 100 mg of ciprofloxacin was weighed and
Bulkiness: dissolved in phosphate buffer pH 7.4 suitable
Bulkiness is the reciprocal of bulk density. It is dilutions was prepared and the solution was analyzed
expressed by cc/g . in UV-double beam spectrophotometer at 278nm
using pH 7.4 as blank.
Compressibility index and Hausner ratio:
The compressibility index and the closely related Thickness:
Hausner ratio have become the simple, fast and Thickness of the tablet was tested using vernier
popular methods of predicting granules flow caliper(Besto). FT-IR Spectral analysis IR Spectral
characteristics. The compressibility index and analysis was used to study the interactions between
Hausner ratio were determined by measuring both the the drug, polymer and the excipients. The drug and
Bulk density and tapped density of granules. excipients must be compatible with one another to
produce a product stable (13). In vitro Release
Compressibility index = (Tapped density-Bulk Studies, for all the formulated tablets were carried out
density / Tapped density) × 100. using USP II paddle method at 50 rpm in 900 ml of
pH 7.4 buffer solution as a dissolution medium, The
Hausner ratio = Tapped density / Bulk density dissolution medium was maintained at 370 ± 0.5 0C.
10 ml of dissolution medium was withdrawn every 30
minutes intervals for 10 hrs. 10 ml of buffer solution
(pH 7.4) was replaced to maintain the constant
volume throughout the experiment. The percentage of
ciprofloxacin released from each formulation was
measured at 278 nm using UV-visible
spectrophotometer (Elico-SL164).

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 IJPRAS, 2012; Volume 1(4)

RESULTS AND DISCUSSION:

A) Characterization And Identification Of Drug

Polymer and Formulation :

Ciprofloxacin drug:

N-H stretching at 3527.25 cm-1,

O-H stretching at 2924.72 cm-1
C-H stretching at 2705.2,705.2,2620.8,2469.4 cm-1
C=O stretching at 1708.54, 16924.98, cm-1
O-H bending at 1273.54, cm-1
C-H out plane blending at 804.97 cm-1

Physical mixture of drug and polymer:

O-H stretching at 35260.03 at cm-1
C-H stretching at 2928.28 cm-1
C=O stretching at 1708.07 cm-1
C-H in bending at 1449.70 cm -1

Ciprofloxacin Prolonged Released formulation:

O-H and N-H stretching At 3435.11 cm-1
C-H Stretching at 2919.34, 2919.34 & 2466.60cm-1
C=O stretching 1708.82 cm-1
C-H in plane bending at 1449.44 cm-1
C-O stretching 1022.89 cm-1

Infrared absorption spectrum of physical mixture of

polymers and ciprofloxacin was studied and
confirmed that there is no interactions with each
other. The spectra shows all the prominent peaks of
drug as well as polymers. IR spectrum indicated
characteristics picks belongs to measure functional
groups. There is no unexpected characteristic IR band
shift in formulation sample also .hence it can be
conclude that there is no significant changes and
behaviour in drug –polymer formulations.

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 IJPRAS, 2012; Volume 1(4)

density is between 0.399- 0.407,bulkiness is between

In the present study, ciprofloxacin controlled release
matrix tablets were prepared by using, two
polymers HPMC K 100M and Guar gum, with three
ratios (0.5, 1.0 and 1.5). A total number of six
formulations were prepared by wet granulation
method. Angle of repose for F1- F6 is between 30-
35,bulk density is between 0.333-0.361,tapped
2.49-3.00 ,compressibility index is between 11-18 is
with in the acceptable limits, and hausners ratio is
between 1.11-1.18 The above values of pre
compression parameters shows the prepared granules
having good flow property. weight variation was
within ±5% it was within the acceptable limit
,hardness was with in 4-10 was within the acceptable
limits, friability was within 1% it was within the
limit, drug content was within 90-110 it was within
the acceptable limits, all formulations showed
uniform thickness. Infra-red (IR) spectroscopy was
used as means of studying drug – polymer
compatibility and confirmed by comparing
undisturbed structure of IR spectra of Ciprofloxacin,
which indicated no drug- polymer interaction.

Table 2: Evaluation of granules

Formulation Angle of Bulk Tapped Bulkiness Compressibility Hausners
Repose (θ) density(g/cc) density (g/cc) index (%) ratio
(g/cc)

F1 32±0.053 0.325±0.017 0.408±0.017 256±0.025 14.18±0.198 1.16±0.116

F2 32±0.037 0.355±0.019 0.361±0.042 3.49±0.525 14.48±0.200 1.11±0.226

F3 33±0.053 0.344±0.018 0.391±0.042 2.59±0.125 13.98±0.980 1.17±0.416

F4 35±0.034 0.311±0.023 0.381±0.112 2.89±0.075 14.05±0.567 1.56±0.146

F5 32±0.054 0.333±0.012 0.434±0.032 2.45±0.075 14.67±0.435 1.36±0.216

F6 35±0.045 0.321±0.013 0.411±0.032 2.50±0.905 14.51±0.459 1.11±0.346

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 IJPRAS, 2012; Volume 1(4)

Table -3 Evaluation of Controlled release matrix tablets of Ciprofloxacin

Formulation Weight variation Hardness Friability (%) Drug content Thickness
(mg) (kg/cm2) (%) (mm)

F1 498± 2.52 5.08±0.13 0.501 ±0.04 99.2 ±0.45 4.3 ±0.02

F2 496± 3.52 5.11±0.43 0.502 ±0.15 95.2 ±0.56 4.4 ±0.04
F3 500± 0.52 4.89±0.73 0.602 ±0.03 99.2 ±0.50 4.7 ±0.09
F4 497± 1.52 5.18±0.33 0.703 ±0.35 96.2 ±0.90 4.3 ±0.09
F5 495± 2.52 5.02±0.45 0.201 ±0.04 94.2 ±0.88 4.2 ±0.08
F6 500± 0.52 4.98±0.13 0.301±0.02 94.2 ±0.48 4.2 ±0.07

Fig. 1: In-vitro release study of ciprofloxacin with different ratio of HPMC K 100 M

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Fig. 2: In-vitro release study of ciprofloxacin with different ratio of Gaur Gum
CONCLUSION:
The matrix containing HPMC K100, gaur gum and
CMC could sustain the release of Ciprofloxacin HCL
from tablet. Formulation of 3 shows maximum
Release I 12hours Duration Due to Increase
Concentration of HPMC K100. HPMC K100 was
found to be the best polymer. And its hardness
friability, thickness give satisfactory result, hence it
was concluded that the formulation 3 is my best
formulation.
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