ISSN: 2320 – 3471(Online)

A Bharathi et.al. Indian Journal of Research in Pharmacy and Biotechnology

FORMULATION DEVELOPMENT AND EVALUATION OF LOPERAMIDE
HYDROCHLORIDE ORALLY DISINTEGRATING TABLETS
A Bharathi*, K Mohan Guptha, Y Uma Jagannadha Rao
KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada-520010, AP, India
*Corresponding author:bharathi_arigela@yahoo.com
ABSTRACT
There is an increasing demand for more patient compliant dosage form and a novel method is
the development of orally disintegrating tablets which dissolve or disintegrates instantly on the patient
tongue or buccal mucosa. It is suited for tablets undergoing high first pass metabolism and is used for
improving bioavailability with reducing dosing frequency to minimize side effect and make it more cost
effective. Loperamide hydrochloride is a drug of choice for diarrhoea. Loperamide hydrochloride has
systemic bioavailability too low due to extensive hepatic first pass metabolism. Hence the main objective
of the study was to formulate orally disintegrating tablets of Loperamide hydrochloride to achieve a
better dissolution rate and further improving the bioavailability of the drug and to get relief from diarrhoea
very quickly. Orally disintegrating tablets prepared by direct compression and using super
disintegrant crosspovidone were prepared and evaluated for the pre- compression parameters such as
bulk density, compressibility, angle of repose etc. The prepared batches of tablets were evaluated for
hardness, weight variation, friability,drug content, disintegration time and in-vitro dissolution profile and
found satisfactory. Among the 6 groups (f1, f2, f3, f4, f5, f6),formulation f4 emerged as the best
formulation and showed rapid dissolution rate i.e. it releases 95% drug in 5 min.
Key Words: Loperamide hydrochloride, orally disintegrating tablets, Aspartame
1. INTRODUCTION
Recent advance in novel drug delivery system aims to enhance the safety and efficacy of the drug
molecule b y formulating a dosage form being for the administration (Kuchekar BS, 2003) Difficulty in
swallowing is experienced by patient such as paediatric, geriatric, bedridden, disabled and mentally ill, including
motion sickness and sudden episodes of allergic attacks, hence resulting in higher incidence of non-compliance
and ineffective therapy2. To improve the quality of life and treatment compliances of such patients fast
disintegrating or orally disintegrating tablets dosage form is a better alternative for oral medication (Yutaka M,
2002). Orally disintegrating tablets are solid dosage form containing medical substances which disintegrate
rapidly, usually within few seconds when placed upon tongue requiring no additional water to facilate
swallowing (Shu T, 2002) It is suited for tablets undergoing high first pass metabolism and is improving
bioavailability with reducing dosing frequency to minimize side effect.
Fast disintegrating tablets are gaining prominence as new drug delivery systems. These dosage forms
disintegrate within a minute with very less quantity of water. This can be achieved by addition of various
superdisintegrants like croscaramellose sodium, crosspovidone, sodium starch glycolate alone or in various
combinations. Due to the fast disintegration of dosage form, patients o b t a i n q u i c k p h a r m a c o l o g i c a l effect
of active pharmaceutical ingredient (Kharwade RS, 2011).
Loperamide hydrochloride is the drug of choice for diarrhoea. It undergoes first pass metabolism and the
resulting bioavailability is too low. Hence, there is a need to develop rapidly disintegrating tablets, which
disintegrate in matter of seconds in the oral cavity, thereby reducing first pass metabolism, increasing the
bioavailability and also to reduce the onset of pharmacological action. Direct compression is one of the technique
requires the incorporation of superdisintegrants into the formulation and use of highly water soluble excipients
achieve faster tablet disintegration. Direct compression does not require the use of water or heat during the
formulation procedure and is the ideal method for moisture and heat-labile medications.
In this study, an effort has been made to formulate orally d i s i n t e g r a t i n g tablets of Loperamide
hydrochloride using crospovidone as superdisintegrant. Objective of study was to enhance dissolution and
absorption of drug, which may produce the rapid onset of action in the treatment of Diarrhoea.
2. MATERIALS AND METHODS
2.1. Materials: Loperamide hydrochloride was obtained as a gift sample from Vasudha phar machem,
Hyderabad, crosspovidone from ISP, USA, Manitol obtained from Roquette, France, Microcrystalline cellulose
obtained from FMC Ireland. All chemicals and reagents used were of analytical grade.
2.2. Preparation of orally disintegrating tablets: Loperamide hydrochloride orally disintegrating tablets were
prepared by direct compression method. Different concentration of excipients was used to prepare different
groups of orally disintegrating tablets. Compositions of various formulations are shown in Table 1. All the
ingredients of the orally disintegrating tablets of Loperamide hydrochloride were weighed, sieved and mixed, and
then finally to the blend Magnesium Stearate and Aerosil were added and compressed on the 8mm standard
concave punch using an 8 station Kambert tablet machine. The total weight of the formulation was maintained
100mg
Table: 1 Formulation design of directly compressible loperamide hydrochloride tablets
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 ISSN: 2320 – 3471(Online)
A Bharathi et.al. Indian Journal of Research in Pharmacy and Biotechnology

INGREDIENTS (mg) F1 F2 F3 F4 F5 F6
Loperamide HCL 2 2 2 2 2 2
Crospovidone 5 5 7.5 7.5 10 10
Microcrystalline cellulose 5 15 5 15 5 15
Mannitol 81.5 71.5 79 69 76.5 66.5
Aspartame 4 4 4 4 4 4
Magnesium stearate 1 1 1 1 1 1
Aerosil 1 1 1 1 1 1
Pepperment 0.5 0.5 0.5 0.5 0.5 0.5

Table: 2 Evaluation parameters of tablets

Formulae Hardness Friability Weight Thickness(mm) Disintegration Wetting

(kg/ cm2) Variation time (sec) time(sec)
(mg)
FI 5.0 0.145 complies 3.50 14 25.34
FII 5.0 0.150 complies 3.50 14 25.46
FIII 5.0 0.140 complies 3.50 13 18.38
FIV 5.0 0.135 complies 3.50 12 18.47
FV 5.0 0.170 complies 3.50 13 20.71
FVI 5.0 0.172 complies 3.50 13 22.92
2.3.
Evaluation of orally disintegrating tablets of Loperamide hydrochloride: All the batches of tablets were
evaluated for various parameters like weight variation, friability, hardness, drug content, disintegration and
dissolution and results reported in Table 2.

Table 3: Dissolution profiles of formulations

Time % Cumulative drug release
(hr) F1 F2 F3 F4 F5 F6 INNOVATOR
5 86±3. 85±1. 92±0 95±1. 89±1.1 92±2.2 99±0.6
10 87±3.
1 87±1.
4 92±0
.6 97±2.
6 93±2.2 96±3.2 99±0.6
20 3
92±2. 3
90±0. .6
93±1 7
97±2. 93±2.2 96±3.2 99±0.6
30 8 6 .7 7
92±2. 92±0. 93±1 97±2. 93±2.2 96±3.2 99±0.6
8 6 .7 7
Figure :1 Comparitive dissolution profiles of F1-F6 with innovator

120
F1
Cummulative % Drug

100
80 F2
release

60 F3
40
F4
20
0 F5
0 10 20 30 40 F6
Time(min) Innovator

2.3.1. Weight variation test (Ansel HC, 1995): Twenty tablets were taken and their weight was determined
individually and collectively on a digital weighting balance. The average weight of one tablet was determined
from the collective weight.
2.3.2. Hardness test (Banker GS, 1987) (Schiermeier S, 2002): The hardness of the tablet was determined using
Dr. Schleuniger Hardness tester.
2.3.3. Friability test: Six tablets from each batch were examined for friability using Roche Friabalator (Tropical
Equipment Pvt. Ltd. Mumbai, India) and the equipment was run for 4min at 25 revolutions per minute. The

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 ISSN: 2320 – 3471(Online)
A Bharathi et.al. Indian Journal of Research in Pharmacy and Biotechnology
tablets were taken out, dedusted and reweighted and % friability was calculated.
%Friability = (Loss in weight/Initial weight) x 100
2.3.4. Wetting time (Sunada H, 2002) (Schiermeier S, 2002): A piece of tissue paper folded twice was kept in
a Petri dish (inter diameter 5.5cm) containing 6ml of purified water. The tablet was placed on the tissue
paper and allowed to wet completely. The time required for complete wetting of the tablet was then recorded
2.3.5. Tablet thickness: Ten tablets were taken and their thickness is recorded using vernier callipers.
Disintegration test: The disintegration test was performed using an USP disintegration apparatus, with
0
distilled water at 37± 2 C. The time reported to obtain complete disintegration of six tablets were recorded and
average was reported.
2.3.6. In vitro Dissolution testing: Dissolution study was conducted for all the formulation using USP Type-II
apparatus (paddle type). The dissolution test was performed using 900 ml of 0.01 M HCl taken as dissolution
0 0
medium at 50 rpm and 37 C± 0.5 C. Five millilitres of aliquots were periodically withdrawn and the sample
volume was replaced with an equal volume of fresh dissolution medium. The samples were suitably diluted and
analysed by HPLC. For comparison, dissolution studies of commercial tablets were also conducted.
3. RESULTS
Loperamide hydrochloride orally disintegrating tablets were prepared by direct compression method.
The compositions of the formulations are shown in the Table1. Table 2 shows the data obtained from the
evaluation of tablets. All batches of the tablets were preliminarily evaluated for various physical parameters such
as hardness, friability, drug content, wetting time, disintegration and dissolution which were reported in Table
no 2. All above properties and value were near to boundary of standard limit. All the tablets maintained
hardness in the range 5.0 kg/cm2. The loss in total weight of the tablets due to friability was in the range of
0.14 - 0.17%. The drug content in different formulation was highly uniform and in the range of 97 - 99%. Wetting
time is used as an indicator of the ease of tablet disintegration and found to be 18.38 - 25.46 sec. The result of
In-vitro disintegration were within the prescribed limits and comply with the criteria for orally disintegrating
tablets, the value were with 12-14sec. In-vitro dissolution studies are shown in Table 3 and Figure 1.
The concept of super disintegrant addition method proved to be beneficial in order to lower the
disintegration time. The quicker disintegration time may be attributed to faster water uptake by the tablets.
Dissolution profiles revealed that, after 5 minutes, formulations F1-F6 showed % drug release of
86,85,92,95,89,92% respectively. Among all the formulations, F4 formulation shows better dissolution efficiency
and rapid disintegration with release of 95% within 5min.
4. CONCLUSION
The Fast disintegrating tablets of Loperamide hydrochloride were formulated by using the
superdisintegrant Crosspovidone. The use of super disintegrant crosspovidone at concentration of 7.5% has given
the better release of drug when compared to other concentrations. The proposed Fast disintegrating formulation
possessed ideal and reproducible characteristics of disintegration time and drug release profile.
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