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INTERNATIONAL JOURNAL OF PHARMA WORLD RESEARCH
(An International Quarterly Published Online Research Journal)
www.ijpwr.com E-mail:editorijpwr@gmail.com
Title:
DEVELOPMENT OF FLOATING MATRIX TABLETS: AN APPROACH
USING NATURAL GUMS.
Sreenivasa Reddy N1*, Mahendra Kumar C B2, Rohith G3, Chandrashekhar M S1.Sindhuabraham4,
1, Department of Pharmaceutics, Government College of Pharmacy, No.2, P.Kalinga Rao road,
Subbaiah circle, Bangalore- 560027, India. E-mail: sreenu_reddyn@rediffmail.com
2 Professor and Principal, St. Mary’s College of Pharmacy, St.Francis street, Secunderabad,-5000025
3 Drugs Testing Laboratory, Palace Road, Bangalore, India.
4 MS Ramaih College of Pharmacy, MSRIT Campus, Gokul, Bangalore- 560054, India.
*Corresponding author
Sreenivasa Reddy N;
E-mail: sreenu_reddyn@rediffmail.com
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ABSTRACT
In this study floating matrix tablets were prepared using Captopril as a model drug. Tablets
containing a mixture of drug along with Xanthan gum, Gum karaya, Gellan gum & Pullulan gum along
with HPMC K4M, PVP K-30, and Sodium bicarbonate were prepared by direct compression. Sodium
bicarbonate was added as a gas generating agent, produced carbon dioxide in the gastric acidic
environment which helped in maintaining the buoyancy. The prepared tablets were evaluated for
physical properties, content uniformity, hardness, friability, floating lag time and in vitro drug release.
Among the studied formulations, F9 was found to be suitable for gastric retention based on evaluation
parameters, which was considered desirable for the drugs with absorption window in upper GIT. The
linear regression analysis and model fitting showed that all these formulations followed Higuchi model,
which had a higher value of correlation coefficient (r). Stability studies of all formulations were
carried out at elevated temperature and humidity conditions of 40±2 o C/75±5% RH and a control
sample was placed at ambient conditions for 12 months. There was no significant change in buoyancy
property and drug content, indicating that the formulations are stable.
Keywords: Captopril, Pullulan Gum, sustained release, intragastric floating tablet
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INTRODUCTION
In recent years, oral dosage forms for gastric retention have drawn more and more attention for their
theoretical advantages in permitting control over the time and site of drug release.1 The real challenge
in the development of a controlled drug delivery system is not just to sustain the drug release, but also
to prolong the presence of the dosage form in the stomach or the upper small intestine until the drug is
completely released in the desired period of time.2 Gastro retentive drug delivery devices are primarily
controlled release drug delivery systems, which gets retained in the stomach for longer period of time,
thus helping in absorption of drug for the intended duration of time. This in turn improves
bioavailability, reduces drug wastage, and improves solubility of drugs that are less soluble at high pH
environment. It also helps in achieving local delivery of drug to the stomach and proximal small
intestine. Gastric retentive drug delivery devices can be useful for the spatial and temporal delivery of
many drugs.3 Many drugs categorized as once a day delivery have demonstrated to have sub optimal
absorption due to dependence on transit time of the dosage form. Therefore, a system designed for
longer gastric retention will extend the time within which drug absorption can occur in small intestine.4
Thus it has been suggested that formulation of drugs with narrow absorption window in a unique
dosage form prolongs gastric residence time and extended absorption phase. The controlled gastric
retention of solid dosage forms may be achieved by the mechanisms of mucoadhesion, flotation,
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sedimentation, expansion, modified shape systems or by the simultaneous administration of
pharmacological agents that delay gastric emptying.5
Gastric emptying of dosage forms is an extremely variable process and the ability to prolong
and control the emptying time is a valuable asset for dosage forms, which reside in the stomach for a
longer period of time than conventional dosage forms. Several difficulties are encountered in designing
controlled release systems for better absorption and enhanced bioavailability.6
Captopril, an angiotensin-converting enzyme (ACE) inhibitor, is used to treat hypertension,
congestive heart failure, and renal syndromes such as diabetic nephropathy and scleroderma, either
alone or in combination with other thiazide diuretics. The half life of Captopril is less than 3 hours and
the presence of food in the gastro intestinal tract reduce its absorption by about 30 to 40 percent.7
MATERIALS & METHODS:
MATERIALS
Captopril was received as a gift sample from Charaka Pharma(p) Ltd, Mumbai. HPMC 4K, Aerosil,
Sodium bicarbonate, Magnesium stearate, Purified talc were obtained as gift samples from Varsha
laboratories, Bangalore. Xanthan gum, Gum karaya, Pullulan gum, Gellan gum was received as gift
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samples from CP Kelco Laboratories, Germany, Emboitics Pharmaceuticals & Micro labs,
Bangalore.
PREPARATION OF FLOATING MATRIX TABLETS
The ingredients were passed through a 80 mesh sieve. The required quantities of Xanthan gum, Gum
karaya, Pullulan gum, Gellan gum, HPMC 4K, PVP-K30, Di calcium phosphate and Sodium
bicarbonate were blended together in a suitable mixer. Captopril was added to the above and the
mixing continued. Magnesium stearate,Talc & Aerosil were finally added and the blend was then
compressed in to tablets by using a 5 mm punch rotary tablet Minipress machine (Rimek RSB-4, ,
Cadmach, Ahmedabad, India). Table 1 gives the details of the various formulations.
Table 1: Composition of floating matrix tablets of Captopril
Ingredients F1 F2 F3 F4 F5 F6 F7 F8 F9
Captopril 12.5 12.5 12.5 12.5 12.5 12.5 12.5 12.5 12.5
Xanthan Gum 75 50 - - 50 - - - -
Gum Karaya 25 25 25 25 50 50 25 25 50
Gellan Gum - - 75 50 - 50 - - -
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Pullulan Gum - - - - - - 75 50 50
Aerosil 20 20 20 20 20 20 20 20 20
HPMC 4K 50 50 50 50 50 50 50 50 50
PVP K-30 20 20 20 20 20 20 20 20 20
Di Calcium Phosphate 14.5 39.5 14.5 39.5 14.5 14.5 14.5 39.5 14.5
Sodium bicarbonate 30 30 30 30 30 30 30 30 30
Magnesium Stearate 1 1 1 1 1 1 1 1 1
Purified Talc 2 2 2 2 2 2 2 2 2
Total 250 250 250 250 250 250 250 250 250
*All the quantities expressed are in terms of milligrams
EVALUATION OF PHYSICAL PROPERTIES OF FLOATING MATRIX TABLETS:
Hardness: The crushing strength of the tablets was measured using Monsanto hardness tester. Three
tablets from each formulation were tested randomly and average reading noted.
Friability: The friability of a sample of 20 tablets was measured using ROCHE Friabilator (Electro
lab) 20 previously weighed tablets were rotated at 25 RPM for 4 minutes. The weight loss of the tablets
before and after measurement was calculated using the following formula:
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Percentage friability = Initial weight – Final weight x 100
Initial weight
Thickness: The thickness of the tablets was measured using screw gauge meter.
Weight Uniformity: The test was carried in conformity with the official method described in I.P.
Twenty tablets from each formulatiions were selected randomly after compression, weighed
individually and average weight was determined. None of the tablets deviated from the average weight
by more than 5%.
Assay of drug content: Ten tablets were randomly sampled from each formulation batch, finely
powdered and individually estimated for the drug content after suitable dilution, using UV-VIS
Spectrophotometer (UV1601, Shimadzu) at 212 nm.5,8,9
In vitro buoyancy study: The in vitro buoyancy was carried out by determining floating lag time .The
tablets were placed in a 100 ml glass beaker containing 0.1N HCl. The time required for the matrix
tablet to rise from bottom to the surface of the glass beaker and float on surface was determined. Total
floating time was measured as buoyancy lag time during in vitro dissolution studies.5,10
Curve Fitting analysis: Mathematical models, zero-order, first-order, Higuchi & Peppas were applied
to analyze the release rate mechanism and pattern11
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In vitro drug release study: In vitro drug release studies for all the formulations were carried out
using tablet dissolution USP II type (paddle method). The dissolution media used was 0.1N HCl,
maintained at 37±0.5°C and the media was rotated at 50 rpm. Aliquots were withdrawn at different
time intervals, filtered and analyzed spectrophotometrically at 212nm for cumulative drug release. The
dissolution studies were conducted in triplicate and the mean values were plotted against time. The
duration of floatation was also noted for each of the formulations.5,8
Stability Studies: The tablets were stored in an aluminum foil and subjected to elevated temperature
and humidity conditions of 40±2°C/75±5% RH and a control sample was placed at an ambient
condition. The samples were withdrawn once a month for 12 months and evaluated for active drug
content, in vitro buoyancy and drug release profile. The results showed that the drug content did not
differ from initial drug content by not more than 3%, indicates formulations are stable.
RESULTS AND DISCUSSION:
The weight variation and thickness of all the floating matrix tablets were determined and found to
comply with the standards of Indian pharmacopoeia. The hardness of all the formulations were in the
range of 4.0±0.02 to4.5±0.002 kg/cm 2. The percentage friability of all the formulations were ranged
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between 0.41±0.02% to 0.59±0.3% (n = 20). The duration of in vitro buoyancy was carried out and the
studies of all the formulations revealed the rate of floating as follows:
F9>F8>F5>F3>F7>F6>F2>F4>F1. Table 2 gives the Floating lag time and total floating time values
of all the formulations. Figure 1 gives the details of the buoyancy test of Formulation F9.
Table 2: Floating lag time and total floating time values for formulations F1- F9.
FormulationFloating lagtime (min)
Total floatingtime (hrs)
F1 12 >24
F2 8 >14
F3 7 >14
F4 10 >14
F5 8 >24
F6 9 >14
F7 9 >12
F8 4 >10
F9 3 >24
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Figure 1: Floating properties of gastro retentive Captopril matrix tablets ( Formulation F9)
(A)at 0 hour,(B) at 30 minutes,(C) after 1 hour, (D)3 hours, (E)5 hours & (F) 8 hours;
Figure (A) at 0 hour Figure (B) at 30 minutes
Figure (C). at 1 hour Figure (D). at 3rd hour
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Figure 1: Floating properties of gastro retentive Captopril matrix tablets ( Formulation F9)
(A)at 0 hour,(B) at 30 minutes,(C) after 1 hour, (D)3 hours, (E)5 hours & (F) 8 hours;
Figure (A) at 0 hour Figure (B) at 30 minutes
Figure (C). at 1 hour Figure (D). at 3rd hour
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Figure 1: Floating properties of gastro retentive Captopril matrix tablets ( Formulation F9)
(A)at 0 hour,(B) at 30 minutes,(C) after 1 hour, (D)3 hours, (E)5 hours & (F) 8 hours;
Figure (A) at 0 hour Figure (B) at 30 minutes
Figure (C). at 1 hour Figure (D). at 3rd hour
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Figure (E) at 5th hour Figure (F) at 8th hour
Formulations were designed as per the Table 1 at various concentrations of Xanthan, Karaya gum,
Gellan gum & Pullulan gum. Formulation F1, F2, F3, F4, F7 & F8 contained same amount of Karaya
gum and varying the other polymer in two different concentrations (1:2 &1:3), where as F5,F6 &F9
contain equal amount of Gum karaya and other polymers(1:1).By comparing the values of In vitro
dissolution studies(Fig 2) the highest drug release was shown by F7 i.e.99.67% with in 5 hours. After
carrying out in vitro studies all the nine formulations, it was concluded that the formulations having
Pullulan gum along with Gum karaya in the ratio 3:1 as polymer matrix exhibits better release of drug
(Table3).
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Table 3: % Cumulative drug release for formulations F1-F9
Sl.No. Formulation% Cumulative Drug Release
1 hr 2 hr 3 hr 4 hr 5 hr 6 hr 7 hr 8 hr
1 F1 35.73 47.25 50.00 59.68 60.48 63.23 63.91 73.02
2 F2 37.97 45.53 52.74 64.26 70.79 77.14 90.03 98.62
3 F3 46.33 57.41 67.70 70.20 75.97 77.84 79.87 88.76
4 F4 44.67 58.41 64.94 76.97 78.35 82.81 91.23 97.59
5 F5 35.22 46.04 53.26 54.12 72.33 84.87 93.12 93.98
6 F6 45.36 62.02 68.38 78.35 82.13 93.12 95.87 97.07
7 F7 50.98 77.86 91.14 98.42 99.67 -- -- --
8 F8 32.98 43.29 55.67 64.26 70.79 77.14 90.03 98.62
9 F9 23.19 28.00 39.69 60.30 72.33 75.42 84.53 92.09
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Figure 2: Drug release profile of Captopril floating matrix tablets for formulations F1-F9
% cdr
Time in hours
The variation in the concentration of polymers may affect the drug release pattern . Theoretically
speaking, this behavior is expected one, since a more amount of polymer will always delays the release.
However when the release of F7 is compared with F1 (figure 01), it was found that F1 has shown
decrease in the release marginally with 73.02 % at 8th Hour against F7 with 97.07% (with in 5 hours).
0
20
40
60
80
100
120
0 2 4 6 8 10
F1
F2
F3
F4
F5
F6
F7
F8
F9
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The drug release behavior of different formulations follows the order
F1<F3<F9<F5<F6<F4<F8<F2<F7.
Above studies revealed that formulation F7 releases the drug at better rate than any other
formulations, this can be attributed to the hydrophilic nature of polymer and pores formed by the
release of CO2.
Whereas Formulations F5, F6 & F9 which contains Gum karaya with Xanthan gum, Gellan gum &
Pullulan gum in the ratio 1:1 have shown 93.98%, 97.07% & 92.09% drug release respectively. The
drug release retardation of F5, F6 & F9 follows the order F9<F5<F6.
In the present work, the drug incorporated is basic in nature and the presence of sodium bicarbonate
makes the polymer soluble to some extent. But, the dissolved polymer also imparts pH changes as it is
acidic in nature. Hence the complex nature of these developments might have lead to the initial slow
release of the drug. By using gum karaya constant in the formulations along with other polymers
which can influence the rate of drug release by retardation to get deserved gastro retentive floating
matrix tablets.
Hence, if the polymer does not modulate the matrix pH, an increase in matrix porosity due to the
dissolution of the polymer is the predominating factor due to which we may see enhancement using
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insoluble fillers and retardation using soluble fillers. Hence, by replacing a portion of the highly
soluble filler with less soluble polymer, a lowering in matrix porosity will be seen and the converse is
true for insoluble fillers. Release Kinetics study carried out by fitting the results obtained for zero
order, first order, Higuchi and Korsemeyer Peppas models and results are compared in table no.4.
Table 4: Zero order & first order kinetics for formulations F1-F9
FormulationCode
Zero Order First Order Higuchi Model Korsemeyermodel(n values)
F1 0.9728 0.7787 0.9731 0.967
F2 0.9678 0.7231 0.9713 0.878
F3 0.9881 0.9569 0.9701 1.578
F4 0.9875 0.9255 0.9660 0.901
F5 0.9902 0.9618 0.9745 1.122
F6 0.9924 0.9123 0.9881 1.577
F7 0.9878 0.8976 0.9887 1.062
F8 0.9975 0.8657 0.9891 1.189
F9 0.9831 0.8745 0.9674 1.554
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For all the 9 formulations, the stability studies were carried out at elevated temperature and humidity
conditions of 40±2°C/75±5% RH and control sample was placed at an ambient condition for a period
of 12 months and it was found that there was no change in buoyancy property of all the 9 formulations.
The drug content was obtained once a month up to 12 months showed that the drug content did not
differ not more than 5% from initial drug content, indicating that the formulations are stable.
CONCLUSION
Formulation F9 gave better controlled drug release and floating properties in comparison to the other
formulations. This formulation took 3 minutes to become buoyant. The gastro retentive floating drug
delivery is a promising approach to achieve in vitro buoyancy and thereby longer gastric retention time
for weakly basic drug by using gel-forming as well as low density polymers like xanthan ,gum karaya,
gellan gum, pullulan gum, HPMC K4M and gas-generating agent sodium bicarbonate. These results
are encouraging because the longer gastric residence time is an important factor which influences the
bioavailability of the drugs included in the prolonged/controlled release dosage forms.
ACKNOWLEDGEMENTS:
I specially thank all the pharmaceutical manufacturers who provided the drug, polymers and
excepients as gift samples for my research work. My sincere thanks to Dr.B.R.Jagashetty, Drugs
Controller for the State of Karnataka, Director, Health & family welfare services, Government of
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Karnataka, and Dr. S. Shashidhara., Principal, Government College of Pharmacy, Bangalore for their
necessary permission & kind support for my research work.
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