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Comparative study of different formulations of chlorpheniramine maleate

orally disintegrating tablets

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Int. J. Pharm. Sci. Rev. Res., 28(2), September – October 2014; Article No. 42, Pages: 234-239 ISSN 0976 – 044X

Research Article

Comparative Study of Different Formulations of Chlorpheniramine Maleate Orally

Disintegrating Tablets
a* b a
Amar Issa , Oussama Mansour , Tamim Hammad
a. Department of Pharmaceutics, Faculty of Pharmacy, Tishreen University, Latakia, Syria.
b. Department of Medicinal Chemistry and quality Control, Faculty of Pharmacy, Tishreen University, Latakia, Syria.
*Corresponding author’s E-mail: [email protected]

Accepted on: 12-08-2014; Finalized on: 30-09-2014.

ABSTRACT
Patient compliance is a key factor in recovery or healing, and hard-to-swallow tablets are one of barriers against patient compliance.
The purpose of this study is to formulate and evaluate different formulations of Orally Disintegrating Tablets (ODTs) of
Chlorpheniramine Maleate. Tablets were prepared by the direct compression method. Three types of diluents were used: lactose,
®
mannitol, and glucose. For each group, 40 mg of five different disintegrants such as crospovidone (kollidon-CL ), microcrystalline
cellulose, microcrystalline cellulose, sodium starch glycolate, and sodium croscarmillose were experimented. The lowest
®
disintegration time (17±2.5 sec) was found in the formulation which contains glucose as a diluent and kollidon-CL as a disintegrant.
®
Followed by the formulation which contains mannitol as a diluent and kollidon-CL as a disintegrant with a disintegration time of
21.16±3.5 sec. These formulations also showed the highest dissolution rate, compared to other formulations. All tablets had a
uniform weight and content. They had good mechanical strength, and all of them released 80% of their chlorpheniramine maleate's
content in less than 30 minutes. Tablets with lower disintegrating time released their active ingredient in less time.
Keywords: Orally Disintegrating Tablets, Chlorpheniramine Maleate, Disintegrants, Diluents, Disintegration time.

INTRODUCTION The pharmaceutical active ingredients, which have been

formulated as ODTs, are still limited worldwide, in spite of

O ne of the greatest challenges facing the

pharmaceutical industry today is how to make
drugs easy to take so that patients positively
enjoy the experience.1-3 Hard-to-swallow tablets are one
their features and benefits. Hence, the present work aims
to prepare and study different formulations of Orally
Disintegrating Tablets of chlorpheniramine maleate by
direct compression method.
of the key barriers to patient compliance, and to obviate
this problem, researchers have developed a new dosage Chlorpheniramine maleate is a first-generation alkylamine
form called Orally Disintegrating Tablets (ODTs) which antihistamine used as a treatment of allergic conditions
disintegrate in mouth rapidly, usually within a matter of such as rhinitis and urticaria. It's known as OTC sedative
seconds, when placed upon the tongue without the need drug because it passes the blood brain barrier.15-17 In
for water.4-6 Thus they are suitable for geriatric, pediatric, addition, Chlorpheniramine maleate has been proved to
and traveling patients who suffer from inaccessibility to have an antidepressant property.18 The bioavailability of
water.7,8 In addition to that, ODTs are able to release the chlorpheniramine maleate is 0.4 and its half time is about
active ingredients rapidly, giving the fast effect that 30 hours. Chlorpheniramine maleate is freely soluble in
9 19-21
needed for some cases like allergy, pain, and anxiety. water and has a pKa=9.2. Chlorpheniramine maleate
Moreover, drug candidates which undergo pre-gastric does not exist in such dosage form.
absorption when formulated as orally disintegrating
MATERIALS AND METHODS
tablets may show increased oral bioavailability.10,11
Materials
The US FDA ODT guideline suggests 30 seconds (in vitro)
as the preferred disintegration time whereas the Chlorpheniramine maleate was received as a gift sample
disintegration time recommended by European from Syphcopharma, Syria. Super disintegrants such as:
pharmacopoeia is less than 3minutes. Crospovidone (Kollidon-CL®: polyplasdon XL-10),
Microcrystalline Cellulose (Avicel PH 101® and Avicel PH
Although different technologies, including molding,
102®), Sodium Croscarmillose (Ac-di-sol®) were obtained
sublimation, direct compression, wet granulation, freeze
as gift samples from Alpha Pharmaceutical Industries,
drying and spray drying, have been used to prepare ODTs
Aleppo, Syria. All other materials like lactose, mannitol,
and have advanced considerably along with the rapid
glucose, sodium saccharin, Aerosil 200 and analytical
market growth of ODTs product, the direct compression
solutions were of analytical grade.
method was reported as the simplest and most cost-
effective ODTs manufacturing procedure. Moreover, the Preparation of Orally Disintegrating Tablets
ODTs prepared by direct compression shows better
Chlorpheniramine maleate ODTs were prepared by direct
physical strength than those prepared by other
compression method according to this united formula:
methods.12-14
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Int. J. Pharm. Sci. Rev. Res., 28(2), September – October 2014; Article No. 42, Pages: 234-239 ISSN 0976 – 044X

Evaluation of prepared tablets

Chlorpheniramine Maleate 4 mg
Weight Uniformity
Disintegrant 40 mg
Twenty randomly selected tablets were weighed
individually. The average weight and the standard
Diluent 238 mg
deviation were calculated.
Aerosil200 1% (3 mg) None of the tablets should deviate from the average
weight by more than ±10% as indicted in the European
Sweetener (Sodium Saccharine) 15 mg pharmacopeia, 2005.12
Content uniformity
Fifteen prepared formulations which have different
diluents and/or different disintegrants are given in Table The content uniformity test is used to ensure that every
1. tablet contains the amount of drug substance intended
with little variation among tablets within a batch.
Table 1: Various formulations of Chlorpheniramine
Maleate ODTs. Ten tablets were selected at random and HPLC (High
Performance Liquid Chromatography) analytical method
was applied to assay the individual content of the active
ingredient in each tablet by pulverizing it to a fine powder
and solute it in 500 ml of HCl 0.01Mas indicated in the
th 22
USP-NF. 30 ed., 2007.
The preparation complies if not more than one (all within
limits) individual content is outside the limits of 85 to
115% of the average content and none is outside the
limits of 75 to 125% of the average content.
Hardness and friability tests
Hardness or crushing strength of the tested Orally
Disintegrating Tablet formulations was measured using
the hardness tester (Erweka D-63150: GmbH/TBH.200,
Germany) as indicated by Niazi, 2004.
The friability of a sample of 20 orally disintegrating tablets
was measured utilizing a LOGAN instrument corp. FAB-2.
Pre-weighed tablets were placed in a plastic chambered
friabilator attached to a motor revolving at a speed of 25
rpm for 4 min.23 The tablets were then de-dusted,
All ingredients were weighed and mixed uniformly reweighed, and percentage weight loss (friability) was
together. The obtained blend was lubricated with aerosol calculated by the equation.
200. The tablets were compressed using single punch
tablet compression machine to get a tablet of 300 mg ℎ
% = × 100
weight containing 4 mg of chlorpheniramine maleate. ℎ
The prepared tablets were divided to three groups of In-vitro Disintegration test
three different diluents: In vitro disintegration time (DT) of the orally
Group A contains lactose disintegrating tablets was determined by placing 10 mL of
phosphate buffer (pH= 7.2) at 25oC in a petri dish of 10
Group B contains mannitol cm diameter.24-27 The tablet was then carefully positioned
Group C contains glucose in the center of the petri dish and the time required for
the tablet to completely disintegrate into fine particles
For each group, five different super disintegrants were was noted. Measurements were carried out in replicates
used: of six tablet (n=6) and mean SD values were recorded.
Crospovidon (Kollidon-CL®: PolyplasdonXL-10), Dissolution Test
Microcrystalline Cellulose (AvicelPH 102®),
®
Microcrystalline Cellulose (AvicelPH 101 ), Sodium Starch Dissolution test of Chlorpheniramine maleate tablets was
Glycolate (Primojel®) and Sodium Croscarmillose (Ac-di- performed according to USP XVIII apparatus II, paddle
sol®). The other ingredients like sodium saccharin as a method (Erweka DT600). Paddle speed was maintained at
sweetener and aerosil 200 as a lubricant were kept 50 rpm and 500 mL of 0.01M HCl was used as the
constant. dissolution medium. Samples (5mL) were collected at

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Int. J. Pharm. Sci. Rev. Res., 28(2), September – October 2014; Article No. 42, Pages: 234-239 ISSN 0976 – 044X

predetermined time intervals (1, 2, 3, 4, 5, 7, 10, 15, 20 Disintegration time was found in the range of17 ± 2.5sec
and 30 min), replaced with equal volume of fresh to 3.13min±16.32sec Tables 2.
medium, and analyzed with HPLC analytical method.22,28-
30 Table 2: Disintegration Time of Group A, B and C
Formulations prepared by lactose, mannitol and glucose
Assay respectively.
HPLC analytical method was used, and a calibration curve
Formulation Disintegrant Disintegration Time
was drawn by a series of Chlorpheniramine maleate
standard solutions which was prepared from a mother A1 Kollidon CL 35.16 ± 3.6sec
solution (28mg/100ml). A2 Avicel PH 102 3.13min ± 16.32sec

A standard solution for each used excipient was also A3 Avicel PH 101 3.02min ± 16.04sec
prepared and analyzed by HPLC method to get their A4 Primojel 56.66 ± 4.63sec
chromatogram.22,28,29 A5 Ac-Di-Sol 55.66 ± 6.05sec
HPLC Parameters B1 Kollidon CL 21.16 ± 3.5sec

HPLC was performed on C-18 column following the B2 Avicel PH 102 3.07min ± 14.71sec
parameters developed by Maithani et al., 2010. 20 µL of B3 Avicel PH 101 2.38min ± 12.9sec
the sample was injected and the analysis was carried B4 Primojel 45 ± 4.47sec
using phosphate buffer (pH=5.8): acetonitrile (55:45) as a
B5 Ac-Di-Sol 40.33 ± 5.08sec
mobile phase at a flow rate of 1 ml/min. Detection was
accomplished by UV spectrophotometer at 255 nm. C1 Kollidon CL 17 ± 2.5sec

RESULTS AND DISCUSSION C2 Avicel PH 102 2.54min ± 8.65sec

C3 Avicel PH 101 2.21min ± 17.7sec
Chlorpheniramine Maleate assay
C4 Premojel 37.83 ± 3.18sec
The typical calibration curve for Chlorpheniramine
C5 Ac-Di-Sol 33.83 ± 2.92sec
Maleate analyzed by HPLC method and detected by UV
spectrophotometer was: Comparative study of ODTs combinations prepared by the
= 116656 − 3775.8 same superd is integrant and different diluents, showed
that the least disintegration time was for group C
= 0.9966 prepared by glucose as a diluent, followed by group B
HPLC showed that all excipients except sodium saccharine prepared by mannitol, then group A prepared by lactose,
had no absorbance of U.V at the same wavelength with respectively. This might be due to the high solubility of
chlorpheniramine maleate, this result matches with that glucose compared to the other two diluents.32
obtained by Dibbern et al., 2002.31 Hence, HPLC method
can cancel this U.V absorption interference and gives
accurate assay results.
Evaluation of Prepared Tablets
Generally, mannitol is desirable in orally disintegrating
The data obtained from post-compression parameters dosage forms, because it gives good mouth feel and a
such as weight variation, drug content, hardness, friability pleasant sweet taste. While comparing the disintegration
were all in boundary of standard limit. time values of different groups to each other, tablet
All the tablets passed weight variation test as the which contain Kollidon-CL as a disintegrant exhibited the
percentage weight variation was within the least disintegration time (17±2.5 sec, 21.16±3.5 sec, and
pharmacopoeial limits. 35.16±3.6 sec for formulations C1, B1 and A1,
respectively) compared to other formulations in the same
The percentages drug contents of all the tablets were group. This might be due to high porosity of Kollidon- CL
found to be in the acceptable limits. which is a cross-linked synthetic polymer.32 Hence, water
The hardness of all prepared tablets were found to be in can get throw the pores rapidly exhibiting high capillary
2
the range of 3.75±0.42 to 15.3±1.51 kg/cm . activity. That can accelerate tablet swelling and
disintegration with little tendency to form gels.
In all the formulations the loss in total weight of the Additionally, as Kollidon-CL is non-ionic compound, the
tablets due to friability was less than 1% (in the range of disintegration is independent of the acidity of gastro-
0.4-0.96%). intestinal tract.
The last two parameters indicated good mechanical Formulations prepared by Ac-di-sol were in the second
strength with an ability to withstand physical and place of disintegration time (33.83±2.92 sec, 40.33±5.08
mechanical stress conditions while handling. sec, and 55.66±6.05 sec for C5, B5 and A5, respectively).

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Int. J. Pharm. Sci. Rev. Res., 28(2), September – October 2014; Article No. 42, Pages: 234-239 ISSN 0976 – 044X

The disintegration time of tablets prepared by Kollidon- The longest disintegration time found was more than 3
CL® was shorter than those prepared by Ac-di-sol because minutes and resulted from the use of Avicel. Those results
of the inner adhesive, fibrous and non-porous structure of emphase that the binding role of Avicel is stronger than
32,33
Ac-di-sol. Hence, the intramolecular bounds must be its disintegrate effect which is also done by the
broken and a hydrophilic network have to be formed for mechanism of swelling.
the swelling and disintegration of tablet. This may delay
Previous results concluded that the least disintegration
tablet disintegration.
time (17±2.5 sec) was for the tablets prepared by
Tablets prepared by primojel were in the third place of Kollidon-CL as a disintegrant and glucose as a diluent,
disintegration time (37.83±3.18 sec, 45±4.47 sec, and followed by tablets prepared by Kollidon-CL and mannitol
56.66±4.63 sec for C4, B4 and A4, respectively). This (21.16±3.5 sec).
might be due to the non-porous structure of primojel and
In vitro dissolution studies are shown in Figure. 1 (a, b, c).
its gel-forming tendency which may reduce the ability of
The cumulative percentage of drug release were within
swelling and disintegrating. 22
pharmacopeia limits.

Figure 1 (a): In vitro dissolution studies for group A formulations (prepared by lactose)

Figure 1 (b): In vitro dissolution studies for group B formulations (prepared by Mannitol).

Figure 1 (c): In vitro dissolution studies for group C formulations (prepared by Glucose).

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Int. J. Pharm. Sci. Rev. Res., 28(2), September – October 2014; Article No. 42, Pages: 234-239 ISSN 0976 – 044X

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Source of Support: Nil, Conflict of Interest: None.

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