Iraqi J Pharm Sci, Vol.27(1) 2018 Time controlled sumatriptan using natural polymers
DOI: http://dx.doi.org/10.31351/vol27iss1pp89-99
89
Preparation and Characterization of Time Controlled Drug Delivery
System of Sumatriptan Using Natural Polymers
Mina Sh. Al-Anbagi *,1 , Nawal A. Rajab ** and Yehia I.Khalil***
*Ministry of Health and Environment, ,Al-Zahraa Allergy and Asthma Consultative Center , Baghdad, Iraq.
** Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq.
*** Department of Pharmacy , Isol Al Deen University College, Baghdad, Iraq.
Abstract
Time controlled drug delivery systems are designed to release the drug after a predetermined lag
time to synchronize the disease circadian rhythm.
Sumatriptan is an effective treatment for acute migraine attacks in which this disease show circadian rhythm
between 6 a.m. and 8 a.m.
The aim of this work is to prepare time-controlled press-coated tablet that was given at bed time to
act at early morning with a lag time of 5.45 hours.
Six formulas of fast dissolving core tablets and three formulas of press-coated tablets were prepared by using
direct compression method using different variables to prepare core tablets which include: different types
and concentrations of superdisintegrants while different concentrations of natural and synthetic polymers
were utilized in preparation of press-coated tablets.
The obtained results showed that formula F4 of core tablet, which contained 25 milligrams of sumatriptan, 5% w/w
sodium starch glycolate and avicel PH 102 as diluent, was the selected formula that showed the fastest and complete release
of sumatriptan. Also, formula C3 of press-coated tablet , which contained pectin: EC100 mpa.s: HPMCK15M in
concentration30 milligrams: 10 milligrams:160 milligrams respectively, was selected as the best coating layer since it gave
5.45 hours lag time .
Keywords: Pulsatile, Sumatriptan, Migraine. Pectin, Ethyl cellulose, Hydroxypropylmethylcellulose.
تحضير وتقييم نظام تسليم دوائي موقوت لدواء السوماتريبتان باستخدام بوليمر طبيعي
***يحيى اسماعيل خليلو **رجب عياشنوال ، 1،*مينا شهاب العنبكي
العراق. بغداد ،،مركز الزهراء التخصصي ألمراض الحساسية والربو وزارة الصحة والبيئة ، *
فرع الصيدالنيات ، كلية الصيدلة ، جامعة بغداد ، بغداد ،العراق. **
بغداد ،العراق. ، كلية اصول الدين الجامعة ،قسم الصيدلة ***
الخالصة
الجرع الصيدالنية التي يسيطر عليها الوقت والتي تم تصميمها إلطالق العنصر الدوائي أنظمة تسليم الدواء النابض هي احدى أشكال
ين ب الفعال بعد فترة زمنية محددة سلفا لمزامنة إيقاع المرض البيولوجية. يظهر الصداع النصفي إيقاعا إيقاعيا مع زيادة ملحوظة في النوبات
( tryptamine1 (5-HT1)هيدروكسي تريبتامين -5فز انتقائي لمستقبالت السيروتونين )سوماتريبتان هو محالسادسة صباحا والثامنة صباحا.
مع فترة تأخر مسيطر على توقيتهامغلفة بالضغط اقراص ، هو عالج فعال لنوبات الصداع النصفي الحاد.الهدف من هذا العمل هو إعداد
الذوبان وثالثة أقراص المغلفة بالضغط باستخدام طريقة الضغط المباشر ساعة.تم تحضير ستة أقراص أساسية سريعة 54.5لتسليم الدواء
كيز اباستخدام متغيرات مختلفة إلعداد األقراص أساسية والتي تشمل: أنواع وتراكيز مختلفة من المواد المسرعات التفتت في حين تم استخدام تر
من F4فة بالضغط.أظهرت النتائج التي تم الحصول عليها أن الصيغة مختلفة من البوليمرات الطبيعية واالصطناعية في تحضير أقراص مغل
كمخفف، w/w sodium starch glycolate and avicel PH 102 %5ملغ من سوماتريبتان، و 55القرص األساسي، التي تحتوي على
، التي تحتوي على االقراص المغلفة بالضغط من C3هي الصيغة المحددة التي أعطت التسليم األسرع والكامل لسوماتريبتان. أيضا، الصيغة
pectin:ethylcellulose 100mpa.s:HPMCK15M على التوالي، تم اختياره كأفضل طبقة ملغم 063ملغم : 03ملغم : 03 في تركيز
ساعات تأخرفي وقت تسليم الدواء. 54.5مغلفة حيث أعطت
النصفي. البكتين، إيثيل السليلوز، هيدروكسي بروبيل ميثيل سيليلولوز.: نبضي، سوماتريبتان، الصداع المفتاحيةالكلمات ا
Introduction
Drug delivery is a term used to describe
systems that carry drugs to their targets in the
body to ensure its therapeutic effect(1). Oral drug
delivery is the most widely utilized route of
administration among all the ways that have been
explored for
systemic delivery of drugs via pharmaceutical
products of the different dosage form(2). It is well
known that conventional drug dosage forms give
instant or fast medication release that provides the
determined amount of the drug to the body
without any rate control.
1Corresponding author E-mail: mimielanbaki@gmail.com
Received: 27/1/2018
Accepted: 14/3/2018
Iraqi Journal of Pharmaceutical Sciences
http://dx.doi.org/10.31351/vol27iss1pp89-99
http://bijps.com/index.php/bijps/index
Iraqi J Pharm Sci, Vol.27(1) 2018 Time controlled sumatriptan using natural polymers
90
This lack of control leads to a lot of complications
inherent to the conventional multiple dosing
regimens, e.g., drug accumulation leading to
toxicities, variable plasma drug level, and poor
compliance. All of above necessitate modification
of traditional drug dosage forms which ushered a
second generation known as the modified drug-
release dosage forms(3). The modified drug-
release dosage forms have a prolonged release of
the drug through the longer duration of time
which may result in more patient compliance and
favorable bioavailability and blood concentration-
time profiles of drugs(4). Several controlled-
release preparations present numerous problems
such as resistance and drug tolerance, and
activation of the physiological system due to
long-term constant drug concentrations in the
blood and tissues(5). From above it becomes clear
that shifting toward the pulsatile drug delivery
system is necessary as it would minimize
drawbacks of second-generation dosage forms.
Pulsatile drug delivery systems are time-
controlled drug delivery system. These systems
are designed to achieve time specific and site-
specific delivery of drugs according to the
circadian rhythm of the body. In
chronopharmacotherapy(timed drug therapy)
drug administration is synchronized with
biological rhythms to produce a maximal
therapeutic effect and minimum harm for the
patient. The pulsatile release is also useful for the
targeting of the drug irritating the stomach or
degradable therein, as well for drugs developing
biological tolerance or with an extensive first-pass
metabolism (6). Pulsatile drug delivery system is
designated as the transient and rapid release of a
certain amount of molecules within a short period
immediately after a predetermined off- release
period, i.e., lag time (7).
Migraine shows circadian rhythm with the
marked increase in attacks between 6 a.m. and 8
a.m.(8). Sumatriptan is a selective agonist at
serotonin 5-HT1 receptors, including 5-HT1B/1D
subtypes. It is an effective treatment for acute
migraine attacks, and the injectable form has also
shown efficacy in the treatment of cluster
headaches. Sumatriptan administered
subcutaneously, orally, intranasally or rectally
was effective in alleviating migraine headache
and in the reduction of other symptoms associated
with a migraine, including nausea, photophobia
and phonophobia(9) .
The main aim of this study is to prepare time-
controlled tablet of sumatriptan to synchronize
migraine attack and to obtain acceptable physical
properties of the tablet.
Materials and Methods
Materials
Sumatriptan was from Avril company,
china, croscarmellose sodium,sodium starch
glycolate, microcrystalline cellulose (avicel PH
102), pectin, ethylcellulose 100mpa.s and
hydroxy propyl methyl cellulose K15M were
from Hangzhou Hyper Chemicals Ltd./China,
polyvinylpyrrolidone K30 ,Mg stearate and talc
were from Samarra Drug Industry/Iraq.
Methods
Preparation of inner layer (fast dissolving core
tablet)
Different powder blends of core tablet
which contain Sumatriptan as an active ingredient
with different types of superdisintegrants
(croscarmellose sodium and sodium starch
glycolate at concentrations 1, 3, 5% (w/w) of total
core tablet weight of sumatriptan) were prepared
to be evaluated for their flow properties and
compressibility before compressing into a tablet
using direct compression method.
Powder mixtures of sumatriptan, polyvinyl
pyrrolidone K30, microcrystalline cellulose
(MCC, Avicel PH-102), croscarmellose sodium
(Ac-Di-Sol), sodium starch glycolate ingredients
were dry blended for 20 minutes, followed by
addition of talc and magnesium stearate as shown
in table1. The mixtures were then further blended
for ten minutes, one hundred milligram of
resultant powder blend was manually compressed
using single biconcave punch machine, with a
6mm punch and die to obtain the round core
tablet(10,11).
Formulation of coating mixed blend for press –
coated tablet
Combination of different ratios of pectin,
ethylcellulose (EC) 100mpa.s and hydroxypropyl
methyl cellulose K15M (HPMCK15M) were
weighed and dry blended for about 10 minutes
and used as a press-coating material for coating
the core tablet to prepare press-coated pulsatile
tablets by direct compression method(10). The
composition of the coat is shown in table 2.
The final tablet was made by press coating the
core tablet and the coating materials using 9-mm
die of the tablet machine, 40% of the coating
material were poured to the die before placing the
core tablet which was covered by the the
remaining 60% then it was compressed by single
punch machine(12).
Iraqi J Pharm Sci, Vol.27(1) 2018 Time controlled sumatriptan using natural polymers
91
Table 1. Composition of core powder blend
Ingredients
(mg)
F1 F2 F3 F4 F5 F6
Sumatriptan 25 25 25 25 25 25
Croscarmellose
sodium
5 3 1
Sodium starch
glycolate
5 3 1
Avicel PH 102 65 67 69 65 67 69
PVPK30 2 2 2 2 2 2
Mg stearate 1 1 1 1 1 1
Talc 2 2 2 2 2 2
Total weight 100 100 100 100 100 100
Table 2. Composition of coat powder blend
Formula C1 C2 C3
Pectin (mg) 20 20 30
Ethylcellulose
100mpa.s(mg)
10 20 10
HPMCK15M
(mg)
170 160 160
Total
weight(mg)
200 200 200
Pre-compression parameters of core and coat
powder blends
Micromeritic properties of core and coat
powder blends were recorded. These properties
include : angle of repose was determined by
taking accurately the weighed quantity of powder
blend into the funnel. The funnel height was
adjusted such that the funnel tip should touch the
apex of the blend. This blend was then allowed to
freely flow through the funnel onto the surface.
From the formed powder cone, radius and height
were measured, and their angle of repose was
calculated using the following equation (13)
tan-1=h/r ......... (1)
Where h and r are the height and radius of the
formed powder cone respectively, and θ is an
angle of repose.
The type of flow according to angle of repose
values are shown in table 3
Table 3. Flow properties and corresponding
angles of repose (14)
Flow property Angle of Repose
(degrees)
Excellent 25-30
Good 31-35
Fair –aid not need 36-40
Passable –may hang
up
41-45
Apparent bulk density and tapped density
The bulk density, as a measure used to
designate packing materials was determined by
transporting the precisely weighed amount of
blend (2 grams) to the graduated cylinder (10
milliliters) with the help of a funnel. The volume
was noted. The proportion of the weight of the
sample to the volume was calculated.
To measure tapped density, the same
quantity of blend (2grams) was transported to a 10
milliliters graduated cylinder and tapped by hand
at a specific height for a fixed number of taps
(100). Average of three determinations was taken.
The tapped density was defined as the ratio of the
sample weight to tapped volume(15).
Carr's index (or % compressibility) and Hausner
ratio(16)
It shows powder flow properties. It is
represented in percentage and is give
Carr's index= (Tapped density– Bulk density)/
Tapped density×100……… (2)
Hausner ratio
It is an indirect index of ease of powder
flow. It is measured by the following formula.
Hausner’s ratio= Tapped density/ Bulk
density…….. (3)
Lower Hausner ratio (<1.25) indicates better flow
properties than higher ones (˃1.25). (17)
Post-compression evaluation for core tablet
hardness test
The crushing strength of the core tablets
was measured using a Monsanto hardness tester.
Five tablets from each formulation batch were
tested randomly, and the average reading was
noted. The hardness is measured in kg/cm2 (18).
Content uniformity
This test applied to core tablet. Ten tablets
were weighed and powdered by using mortar and
pestle. The powder which is equivalent to 25 mg
of sumatriptan was weighed and dissolved in 0.1
N HCl solution (pH 1.2).
Iraqi J Pharm Sci, Vol.27(1) 2018 Time controlled sumatriptan using natural polymers
92
The solution gained was filtered, and one mL of
the filtrate was appropriately diluted and analyzed
for Sumatriptan spectrophotometrically at its λ
max (19, 20).
In vitro disintegration time for core tablets
The disintegration test was done for all
core tablet formulas at 37˚C using phosphate
buffer (pH 6.8) as disintegration media.
Disintegration apparatus of a one-liter cylinder
with a basket rack assembly containing six open-
ended tubes and 10-mesh screen on the bottom
was used. A tablet was placed in every tube of the
basket and the time required for complete
disintegration of the tablets with no palpable mass
remaining in the apparatus was measure(14).
In-vitro dissolution test
In-vitro dissolution test is applied for core
tablet using USP apparatus type II (paddle) at 37
± 0.5°C in 900 milliliters of dissolution medium
(phosphate buffer pH 6.8 ) at 50 rpm. Five
milliliters samples were withdrawn periodically at
different time intervals, and each sample was
substituted with an equal volume of fresh
dissolution medium. Then, the samples were
filtered and analyzed spectrophotometrically at its
λ max. Each test was done in triplicate. For
optimization many variables evaluated to test its
effect on the dissolution of the core tablet from
different formulas (21).
Post-compression evaluation for press coated
tablet
The prepared coated tablets were
evaluated for hardness and release study for press
coated tablet as mentioned for core tablets.
In-vitro release studies of press-coated pulsatile
tablets
The prepared press coated tablets were
examined for in vitro drug release in two
different suitable dissolution media( 2 hours in 0.1
N HCl (pH 1.2) followed by 4 hours in phosphate
buffer pH 6.8) using USP type II dissolution
apparatus at 50 rpm to assess their ability to
provide the desired lag time before drug release.
Five milliliters samples were withdrawn
periodically at different time intervals, and each
sample was substituted with an equal volume of
fresh dissolution medium. Then, the samples were
filtered and analyzed spectrophotometrically at its
λ max(22).
Variables effecting release of sumatriptan from
the core tablet
Effect of type of superdisintegrants
Two different types of superdisintegrants
(croscarmellose and sodium starch glycolate) at
5% concentrations were used in (F1 and F4) to
study the effect of superdisintegrant types on the
drug release properties from sumatriptan core
tablet.
Effect of concentration of superdisintegrant
Different percentages of sodium starch
glycolate (superdisintegrant) were utilized in the
formulation of core tablet formula (F6, F5, F4 )
containing 1,3 and 5% to analyze the effect of
using different concentrations of sodium starch
glycolate on sumatriptan release from the core
tablet.
Variables affecting the release of sumatriptan
from the press coated core tablet (effect of
different concentrations of combination of
polymers)
Three formulas of coated core tablet were
made using different polymers (Pectin,
ethylcellulose 100mpa.s and HPMCK15M) in
different ratios as recorded in table 2 to study their
effect on sumatriptan release from press coated
core tablet and also their effect on the lag time
required for release of the drug.
Drug – excipients compatibility studies
Physicochemical compatibility between
sumatriptan and different excipients was studied
using Fourier transform infrared spectroscopy
(FTIR) and differential scanning calorimetry
(DSC).
1.Fourier transform infrared spectroscopy
(FTIR)
The pure drug powder and the optimum
formula of core tablet (F4) were analyzed
individually by using (Shimadzu 8300, Japan)
according to KBr disk method. About 2-3
milligrams sample was mixed with dried IR grade
potassium bromide powder to form a uniform
blend of about 200 milligrams, and analyzed by
FTIR spectroscopy at 4000-400 cm-1(23).
2.Differential scanning calorimetry (DSC)
It was carried out by the same way for the
pure drug powder, and the physical mixture of the
optimum formula of core tablet F4 , and the
optimum formula of core tablet F4 using
Differential Scanning Calorimeter (Shimadzu
DSC- 60). Samples were heated in an aluminum
sample pans at a rate of 10°C/minute over a
temperature up to 350 °C under a nitrogen flow of
50 milliliters/minute (24).
Statistical analysis
The results of the experiments were given
as mean values ± standard deviation (SD) and
analyzed according to the one-way analysis of
variance (ANOVA) at which significant results
(p<0.05) and non-significant (p>0.05)(25).
Iraqi J Pharm Sci, Vol.27(1) 2018 Time controlled sumatriptan using natural polymers
93
Result and Discussion
Pre-compression parameters of core powder
blend
The values of angle of repose, bulk
density, tapped density, Carr's index, and Hausner
ratio for each prepared core and coat powder
blend formula were measured .The results of
precompression evaluation tests of core powder
blend are illustrated in table 4. These results
estimated according to USP (20). The results show
that the prepared core mixtures have acceptable
flow properties and compressibility.
Table 4. Pre-Compression Physical Parameter’s for Core Powder Blend of Sumatriptan
F
o
r
m
u
la
Angle of
repose
(Degree)
Mean± SD,
n=3
Bulk density
(g/cm3)
Mean± SD, n=3
Tapped density
(g/cm3)
Mean± SD, n=3
Carr's index
Mean± SD, n=3
Hausner ratio
Mean± SD, n=3
Type of
flow
F1 17.51±0.03 0.5460.01 0.608±0.02 10.21±1.36 1.11±0.019 Excellent
F2 18.4 0.1 0. 4950.08 0.57±0.021 10.51±1.0002 1.12±0.02 Excellent
F3 25.70.2 0.560.56 0.632±0.03 10.73±0.37 1.119±0.004 Excellent
F4 21.360.56 0.33±0.05 0.371±0.03 10.84±0.39 1.122±0.005 Excellent
F5 19.250.75 0.3450.01 0.357±0.015 3.41±0.15 1.041±0.007 Excellent
F6 20.5±0.4 0.311±0.026 0.334±0.028 6.92±0.2 1.07±0.001 Excellent
Postcompression evaluation of core tablet:
Hardness, content uniformity and in-vitro
disintegration study of core tablets
Hardness testing of solid oral dosage forms
is essential because it provides a quantitative
estimate of the internal bonding strength of the
powder compact, since it gives the tablet
sufficient mechanical strength to keep its internal
structure and geometry under applied external
forces. Differences in tablet hardness are hence
known to correlate with differences in dissolution
or mechanical response during any
postcompression operations such as tablet
coating, handling, packaging, storage, or
shipping(26).
The results of hardness test for all prepared
core tablet formulas were in the range of ( 4.1-
4.53 Kg/cm2) as shown in table 5 which indicate
the tablets had adequate strength property to resist
handling, shipping and tablet coating.
The results of drug content test are shown in table
5 that all prepared core tablets had acceptable
range according to USP pharmacopeia (14).
The results of disintegration test of all prepared
core tablets are shown in table 5. In this study, two
types of superdisintegrants were used , CCS and
SSG had three different
concentrations(1%,3%,5%) w/w of total weight
of sumatriptan core tablet.
As shown in table 5, F1 and F4 that contained
5%(w/w) croscarmellose sodium and 5% (w/w)
sodium starch glycolate respectively, F4 had the
shortest disintegration time, this may be due to the
remarkable rapid water penetration and extensive
swelling capability of SSG. SSG was reported to
possess the capability to absorb water and swell
about 300 times its volume and not affected by an
increase in compression pressure(27).
The results showed that F2 which contains 3%
croscarmellose sodium had shorter disintegration
time than F1 that contains higher concentration of
this superdisintegrant which may be due to partial
gelling that potentially could form a viscous
barrier and delay the entry of water into the tablet
leading to this delay in the disintegration of tablets
of F2(27).
In case of the superdisintegrant sodium starch
glycolate was used in formulas F4, F5 and F6 in
concentrations 5%, 3% and 1% (w/w)
respectively. It was observed that the
disintegration time was decreased as the
concentration of the superdisintegrant was
increased from concentration 1% to 5% (w/w).
Iraqi J Pharm Sci, Vol.27(1) 2018 Time controlled sumatriptan using natural polymers
94
Table 5 . Physical evaluation of core tablets of
sumatriptan
F
o
r
m
u
la
Hardness
(kg)
Mean±
SD, n=5
Content
uniformity
%
Mean± SD,
n=3
Disintegra
tion time
seconds
Mean±
SD, n=6
F1 4.1±0.13 97.31±0.77 14.25±0.95
F2 4.22±0.17 96.17±0.47 11±4.89
F3 4.52±0.32 98.07±0.45 17.5±2.5
F4 4.43±0.3 98.48±2.6 8.8±1.4
F5 4.7±0.2 95.15±1.08 11.67±1.6
F6 4.78±0.2 96.712±0.95 21.5±2.25
In-vitro release studies of core tablets
Figure 1 shows that F4 has faster
dissolution rate where 100% release of
Sumatriptan from core tablet obtained in 2
minutes this significant difference (p≤ 0.05), this
was explained that sodium starch glycolate
possesses the additional advantages of being
soluble and readily dispersible in water. Its
spherical particles, dispersed in a tablet system,
offer a larger surface, thus allowing rapid
penetration of water into the tablet interior. The
main reasons for the efficiency of this disintegrant
probably are its high rate of water uptake and its
marked swelling properties; these factors cause
pressure to be exerted within the tablet, thus
breaking up interparticle bonding. This is then
followed by the dissolution of sodium starch
glycolate particles, which results in the crumbling
and disintegration of the entire tablet structure (28).
SSG may swell up to three hundred times its
original volume in water(29).
Formulas F4, F5, and F6 contain different
concentrations of sodium starch glycolate used to
study the effect of superdisintegrant concentration
on the release of Sumatriptan from core tablets as
shown in figure 2. F4 which contains 5% w/w
sodium starch glycolate show higher percent of
drug release. There was significant difference
(p≤0.05) in dissolution rate between the formulas
because as we increase in the concentration of
superdisintegrant, the disintegration time will
decrease. This disintegration is reported to affect
dissolution characteristics as well(30).
Figure 1. Effect of superdisintegrant type on
drug release from core tablet (phosphate
buffer pH 6.8, temp. 37 0C)
Figure 2. Effect of sodium starch glycolate
concentration on drug release from
sumatriptan core tablet (phosphate buffer pH
6.8, temp. 37 0C)
To prepare pulsatile press coated tablet, F4
(that contains 5% (w/w) sodium starch glycolate
as superdisintegrant and avicel PH 102 as diluent)
was selected as the optimum core part since it
produced the fastest 100% release of sumatriptan
within 2 minutes.
Post compression evaluation of press-coated
pulsatile tablet
The results of hardness of all the press-
coated tablets were shown in table 5. These results
show that all the prepared press-coated tablets
formula agrees with the requirements of USP. The
hardness of the press-coated tablets was kept
constant in the range 6-7 kg/cm2 by mounting the
Iraqi J Pharm Sci, Vol.27(1) 2018 Time controlled sumatriptan using natural polymers
95
compression force of the machine to eliminate the
variability in hardness. The hardness of the press
coated tablets slightly increased as ethyl cellulose
concentration was increased due to high
compressibility of this polymer (31).
Table 6. Post formulation results of press
coated core tablet of sumatriptan
Formula Hardness (kg/cm2)
C1 6.25±0.4
C2 6.75±0.06
C3 6.25±0.04
In-vitro release studies of press-coated pulsatile
tablets
Formulas C1 –C3 were used to study the
effect of the combination of natural and synthetic
polymers in different proportions (pectin,
ethylcellulose100 mpa.s and HPMCK15M).
Ratios of the polymers used were 10:5:85,
10:10:80 and 15:5:80 w/w of coating layer;
respectively. C1 and C2 was used to assign the
effect of ethylcellulose 100 mpa.s and
HPMCK15M on the lag time. It was noticed that
as the ratio of HPMC increased the lag time will
be decreased due to hydrophilicity nature of
HPMC. C2 and C3 were used to observe the effect
of pectin and ethylcellulose 100 mpa.s on lag
time; it was observed that as the ratio of pectin
was increased the lag time was decreased because
of hydrophilic nature of pectin and its inherited
swelling and eroding behavior (32).
The results of In-vitro release studies of
press-coated pulsatile tablets are shown in table 7.
Table 7. Lag time of dissolution for different
coating formulas of sumatriptan press-coated
tablet
Formula Composition
Lag
time
in h:
min
C1 Pectin:EC100:HPMCK
15M 10:5:85
6:20
C2 Pectin:EC100:HPMCK
15M 10:10:80
7
C3 Pectin:EC100:HPMCK
15M 15:5:80
5:45
Coat formula C3 was chosen as coat for
optimum core tablet formula F4 since it gave it
gave 100% release the drug after 5.45 hours lag
time, which is required to provide a maximum
concentration of drug at the time of its maximum
need.
Release profile of the press coated system of
sumatriptan as shown in figure (3).
Figure 3. Release profile of sumatriptan from
the selected final sumatriptan press-coated
tablet
Drug – excipients compatibility studies
Compatibility studies were assigned by using :
Differential Scanning Calorimetry (DSC)
The DSC technique had been used
for chemical stability and compatibility
studies(33). The differential scanning
calorimetry (DSC) of sumatriptan pure
drug, the physical mixture of optimum core
tablet and the optimum core tablet of
Sumatriptan were performed using a
Shimadzu 8300 DSC, and the DSC
thermogram of all samples had been shown
in figures (4-6). The DSC thermogram of
sumatriptan pure drug, the physical mixture
of optimum core tablet and sumatriptan
optimum core tablet exhibited the
characteristic drug peak indicating
compatibility and absence of interaction
between the drug and the other components
(34).
Iraqi J Pharm Sci, Vol.27(1) 2018 Time controlled sumatriptan using natural polymers
96
Figure 4. DSC thermogram of pure
sumatriptan
100.00 200.00 300.00
Temp [C]
-4.00
-3.00
-2.00
mW
DSC
77.67x100C
169.56x100C
Figure 5. DSC thermogram of physical
mixture of sumatriptan core tablet
100.00 200.00 300.00
Temp [C]
-1.00
0.00
1.00
2.00
3.00
mW
DSC
170.40x100C
Figure 6. DSC thermogram of sumatriptan
optimum core tablet
Fourier Transform Infrared Spectroscopy
(FTIR):
FTIR spectrum of pure sumatriptan drug
and the selected core tablet are shown in figures 7
and 8 respectively.
In figure 7 it was found the characteristic peaks of
sumatriptan pure drug at 3373 cm-1, 1298 cm-1,
1236 cm-1, 1082 cm-1 and 636 cm-1 belongs to N-
H Stretching vibration, C-N stretching vibration,
S=O stretching vibration and C-S stretching
vibration, respectively.
In figure 8, the characteristics peaks of
sumatriptan were found in core tablet were for N–
H str. Primary amine at 3391 cm−1, C–N str. at
1299.79 and 1233.26 cm−1, and C–H str. at 2960–
2850 cm−1 and S=O str. at 1057.76 cm-1 and C-S
str. at 638 cm-1 (39).Figure 8 shows the FTIR
spectrum of the selected formula of the core tablet
F4 containing sumatriptan. There were no
significant differences in the main characteristic
bands of the drug indicating no interaction
between drug and other additives in core tablet
formula F4.
Iraqi J Pharm Sci, Vol.27(1) 2018 Time controlled sumatriptan using natural polymers
97
Figure 7. FTIR spectrum of sumatriptan
Figure 8. FTIR spectrum of the selected formula of sumatriptan core tablet
Conclusion
Press coated tablet of sumatriptan with
core tablet containing avicel PH 102 as a diluent
and 5% w/w of SSG as a superdisintegrant and
coating layer containing combination of
polymers which are pectin ,ethylcellulose
100mpa.s and HPMCK15M in concentration 30
mg:10 mg :160 mg respectively provides
optimum lag time required to synchronize the
migraine attack
References
1. Tiwari G, Tiwari R, Sriwastawa B, Bhati L,
Pandey S, Pandey P, Bannerjee SK. Drug
delivery systems: An updated review.
International journal of pharmaceutical
investigation. 2012;2(1):2.
Iraqi J Pharm Sci, Vol.27(1) 2018 Time controlled sumatriptan using natural polymers
98
2. Susanta Kumar Rout et al. A Brief Review on
Modified Release Solid Dosage Form with
Special Reference to Design. Ijppr.Human,
2015;2 (2): 25-40.
3. P. Tripura Sundari et al. Abuse resistant
dosage forms: A redress to modified release
dosage forms. J. Chem. Pharm. Res. 2016;
8(5):229-242.
4. Bhargava A et al. Oral sustained release
dosage form: an opportunity to prolong the
release of drug. IJARPB. 2013; 3(1): 7-14.
5. Lin SY, Kawashima Y. Current status and
approaches to developing press-coated
chronodelivery drug systems. Journal of
controlled release. 2012;157(3):331-353.
6. Singh NP, Ganarajan G, Kothiyal P. Pulsatile
drug delivery system: a review. World J
Pharmacy Pharm Sci. 2016 Mar 9;5:479-491
7. Amit K, Sonam R. 9. Pulsatile Drug Delivery
System: Method and Technology Review.
International Journal of Drug Development
and Research. 2012.
8. Solomon GD. Circadian rhythms and
migraine. Cleveland Clinic journal of
medicine. 1992;59(3):326-329.
9. Perry CM, Markham A. Sumatriptan. Drugs.
1998;55(6):889-922.
10. Bonthagarala B, Vadrevu S, Nama S,
Sudarshan D, Nuthakki S. Formulation and
evaluation of pulsatile drug delivery system of
atenolol. American Journal of Biological and
Pharmaceutical Research. 2014; 1(1): 28-33.
11. Bisht SS, Chaurasia H, Varshney S, Kotiyal
D. Formulation and evaluation of fast
dissolving tablets of sumatriptan succinate.
International Journal of Pharmaceutical
Sciences and Research. 2013 ; 4(5):1912-
1917.
12. Maity S., Sa B., Compression-coated tablet
for colon targeting: Impact of coating and core
materials on drug release, AAPS Pharm
SciTech, 17, 2015, 504-515.
13. Shaikh AC, Nazim S, Siraj S, Khan TA, Patel
MS, Zameeruddin MO, Shaikh AR.
Formulation and evaluation of sustained
release tablets of aceclofenac using
hydrophilic matrix system. International
Journal of Pharmacy and Pharmaceutical
Sciences. 2011;3(2):145-148.
14. The United States Pharmacopoeia (USP) 36,
USA. The United States Pharmacopeial
Convention Inc. 2012.
15. Mohd AH, Rao NG, Avanapu SR. Matrix-
mini-tablets of lornoxicam for targeting early
morning peak symptoms of rheumatoid
arthritis. Iranian journal of basic medical
sciences. 2014; 17(5):357-369.
16. Tejaskumar P, Ananthapur M, Sabitha JS,
Tribedi S, Mathappan R, Prasanth VV.
Formulation and Evaluation of Erodible
Pulsatile Drug Delivery System of Salbutamol
Sulphate for Nocturnal Asthma. International
Journal Of Pharmaceutical Innovat Ions.
2013; 3(3):24-35.
17. Govedarica B, Injac R, Srcic S. Formulation
and evaluation of immediate release tablets
with different types of paracetamol powders
prepared by direct compression. African
Journal of Pharmacy and Pharmacology.
2009; 5(1):31-41
18. Nama M, Gonugunta CS, Veerareddy PR.
Formulation and evaluation of gastroretentive
dosage forms of clarithromycin. AAPS
PharmSciTech. 2008;9(1):231.
19. L.V. Allen, N.G. Popovich, H.C. Ansel,
Ansel's Pharmaceutical Dosage Forms and
Drug Delivery Systems, 9th ed. Lippincott
Williams & Wilkins, Philadelphia, 2010
20. Aslani A, Beigi M. Design, formulation, and
physicochemical evaluation of montelukast
orally disintegrating tablet. International
journal of preventive medicine. 2016;7.
21. R. Gowri et al. Ranitidine Hydrochloride
Floating Tablets of Intragastric Drug Delivery
-Formulation and Characterization.
Ijppr.Human. 2014;2 (2): 88-97.
22. Nayak M., Patel U., Bhimani B., Patel G.,
CHaudhry S..Formulation and evaluation of
pulsatile tablet of nebivolol for
chronopharmacotherapy of hypertension .
International Journal of Pharmaceutical
Research and Bio- Sciences. 2015 ;4:388-401.
23. Manikandan M, Kannan K, Manavalan R.
Compatibility studies of camptothecin with
various pharmaceutical excipients used in the
development of nanoparticle formulation. Int
J Pharm Pharm Sci. 2013;5(4):315-321.
24. Vallabhbhai Pansuriya et al. Formulation and
optimization of compress coated pulsatile
tablet of doxofylline chronopharmaceutical
approach for treatment of nocturnal asthma.
International Journal of Pharmacy &
Pharmaceutical Research. 2015; 2(4): 129-
143.
25. Alkazzaz SZ, Ali WK. Design and In-Vitro
Evaluation of Colon Targeted Prednisolone
Solid Dispersion Tablets. Uk journal of
pharmaceutical and biosciences. 2015;3(6) :
30-41.
Iraqi J Pharm Sci, Vol.27(1) 2018 Time controlled sumatriptan using natural polymers
99
26. May RK, Su KE, Han L, Zhong S, Elliott JA,
Gladden LF, Evans M, Shen Y, Zeitler JA.
Hardness and density distributions of
pharmaceutical tablets measured by terahertz
pulsed imaging. Journal of Pharmaceutical
Sciences. 2013; 102(7):2179-2186.
27. Vidyadhara S, Sasidhar RL, Deepti B, Vikas
S. Formulation of fast dissolving tablets for
olmesartan using hydroxy propyl β-
Cyclodextrins. Der Pharmacia Lettre. 2016; 8
(13):115-125.
28. Khan KA, Rhodes CT. Water‐sorption
properties of tablet disintegrants. Journal of
pharmaceutical sciences. 1975; 64(3):447-
451.
29. Battu SK, Repka MA, Majumdar S, Rao Y M.
Formulation and evaluation of rapidly
disintegrating fenoverine tablets: effect of
superdisintegrants. Drug development and
industrial pharmacy. 2007;33(11):1225-1232
30. Nitalikar MM, Sakarkar DM. Formulation
development and characterization of fast
disintegrating tablets of Nimesulide. Stamford
Journal of Pharmaceutical Sciences. 2012 Apr
21;4(2):25-28.
31. Maraie NK, Albahadily AA. Efficacy of
Preparation of Time Programmed Double
Pulse Press Coated Tablet containing Fixed
Dose Combination of Montelukast Sodium
and Levocetrizine dihydrochloride for
Treatment of Nocturnal Asthma. International
Journal of Pharmaceutical Sciences Review
and Research. 2016; 41(2): 306-311.
32. Sriamornsak P, Thirawong N, Weerapol Y,
Nunthanid J, Sungthongjeen S. Swelling and
erosion of pectin matrix tablets and their
impact on drug release behavior. European
journal of pharmaceutics and
biopharmaceutics. 2007; 67(1):211-219.
33. Balpande HM, Raut NS, Umekar MJ,
Kotagale NR. Compatibility study of
metformin with pharmaceutical
excipients.International Journal of Chem Tech
Research. 2013; 5(4): 1684-1693.
34. Abd-El Bary A, Louis D, Sayed S. Liquisolid
tablet formulation as a tool to improve the
dissolution of olmesartan medoxomil. Inventi
Journals 2014; 3: 1-8.