Pharmaceutical Resonance 2018 Vol.

1 - Issue 1

RESEARCH ARTICLE

Formulation and Evaluation of Rectal Delivery System for the

Treatment of Hemorrhoids

Suchita Dhamane1*, Aditi Kulkarni 2. Potnis Vaishali1, Manoj Modase2

1
Department of Pharmaceutics, JSPM’s Jayawantrao Sawant college of Pharmacy and Research, Hadapsar, Pune.
2
Department of Pharmacognosy, JSPM’s Jayawantrao Sawant college of Pharmacy and Research, Hadapsar, Pune.

ABSTRACT:The aim of this research was to introduce rapid onset of action of lidocaine in relief of pain and inflammation
in treatment of haemorrhoids. Haemorrhoids are swollen and inflamed veins in the rectum and anus that cause discomfort
and bleeding. Rectal delivery of drugs promotes rapid absorption and high bioavailability, with a subsequent immediate
onset of pharmacological effect. Conventional suppositories are solid forms which often cause discomfort during insertion.
The leakage of suppositories from the rectum also gives uncomfortable feelings to the patients. In addition, when the solid
suppositories without mucoadhesivity reach the end of the colon, the drugs can undergo the first-pass effect. To solve these
problems, we developed a novel in situ-gelling and mucoadhesive lidocaine liquid suppository with gelation temperature at
30–36°C and suitable gel strength and bioadhesive force. The mixtures of P407 (25%) and P188 (5%) existed as a liquid at
room temperature, but gelled at 30–36°C. To modulate gel strength and mucoadhesive force, mucoadhesive polymers such
as HPMC K4M and carbopol 940 was used. Optimized formulation was tested in haemorrhoids induced rats for 5 days.
After 5 days of treatment with optimized formulation histopathological studies reveals that there was significant reduction
in inflammation as compared to positive group.
Keywords: Haemor r hoids, liquid suppositor y, mucoadhesive, lidocaine
1. Introduction depolarization, blocking transmission of nerve impulses.
This helps in reducing the pain while passing bowels. It
A conventional suppository is a semi solid dosage form
also shows anti-inflammatory properties. Pure aloe vera is
which melts in the rectum at body temperature [1]. The
used to treat pain and inflammation. Hence, combination
patient compliance for conventional suppository is less as
of lidocaine and aloe Vera was used for preparation of
it causes discomfort and sometimes refusal. Conventional
liquid suppository.
suppository may undergoes first pass metabolism as it
reaches to the end of rectum [2,3] Therefore, an attempt 2. Experimental
was made to develop a liquid rectal dosage form which
2.1 Materials
forms a gel at body temperature, with suitable gel strength
that does not leak out of the anus after administration and Lidocaine was obtained from Titan Laboratory, India,
has suitable bio adhesive force so as not reach at the end Poloxamer 407 and poloxamer 188 were from BASF,
of the colon. Liquid suppositories aimed either to improve Germany; HPMC K4M from Emcure Pharmaceutical Ltd,
the local effect or to enhance the drug absorption.[3,4] Pune and Carbopol 940 from New Modern Chemical
Poloxamer are the base of the liquid suppositories. corporation, Mumbai and aloe vera juice from Patanjali
Poloxamer solutions are known to exhibit phenomenon of Ayurveda.
reverse thermal gelation remaining as solution at low 2.2 Methods
temperature (40oC) and gelling upon increasing the
temperature to 25-35oC.[5,6] 2.2.1 Pre-formulation Studies [6,7]
Lidocaine belongs to class of local anaesthetic. 2.2.1.1. UV-spectrophotometric study of lidocaine
Lidocaine increases permeability to sodium ions in
neuronal membranes, resulting in inhibition of Stock solutions of Lidocaine (100 μg/ml) was prepared by
dissolving accurately weighed 10mg quantity using 100
ml distilled water. From stock solution 1 ml was diluted
* Dahmane Suchita with distilled water to give solutions of 10 μg/ml
Department of Pharmaceutics concentration. The solutions were scanned in the range of
JSPM’s Jayawantrao Sawant college of Pharmacy and
400 to 200 nm and respective λ max values were reported
Research, Hadapsar, Pune
Email : spd.jscopr@gmail.com in triplicate. Calibration curve of lidocaine in distilled

© Published by DYPIPSR, Pimpri, Pune - 411 018 ( MH ) INDIA 42

 Pharmaceutical Resonance 2018 Vol.1 - Issue 1

water was prepared in distilled water and phosphate buffer 407 and poloxamer 188 were two factors with three
pH 6.8. different concentrations. Concentration of polymers was
selected based on evaluation of preliminary placebo
2.2.1.2. IR spectrometry
suppository batches. Formulations were optimized by
The IR absorption spectrum of Lidocaine was recorded by application of 32 full factorial designs, to study effect of
potassium dispersion method. The drug was previously concentration and type of polymer on gelation temperature
dried in desiccator and then spectrum was recorded by and drug release at the end of 5 hrs.
blending with potassium bromide. For this, sample of drug
and potassium bromide was mixed in a 1:3 ratio and kept Table 2. Differ ent batches with their r espective
in sample cell. The cell was then fitted on sample holder compositions as per (32) factorial design
and an IR spectrum was recorded 4000-400 cm-1 after Formulation X1: Poloxamer X2: Poloxamer
baseline correction was made. code 407 188
2.2.2 Drug-excipient compatibility studies MF1 5 1
The compatibility of mixture of Lidocaine with or without MF2 15 1
polymeric addition was ascertained by exposing to the
environmental conditions over the 15 days. The detection MF3 25 1
of changes in any of the physical or physicochemical MF4 5 3
characteristics of blends if any was carried out by visual
and FT-IR spectrophotometry (Jasco 4600, USA). MF5 15 3

2.2.3 Preparation of liquid suppository MF6 25 3

Formulation and evaluation of placebo liquid MF7 5 5

Suppository
MF8 15 5
Placebo liquid suppositories were prepared to determine
optimum concentration of polymer. Prepared suppositories MF9 25 5
were evaluated for gelling temperature, gel strength and
gelling time and gelling ability. All excipients except All nine formulations of medicated liquid suppositories
poloxamer as given in table no.1 were completely were evaluated for colour, clarity, pH, gelation
dispersed in distilled water with continuous agitation at temperature, gel strength, drug content and drug release
room temperature and cooled to 4°C. Poloxamer was then through dialyzing membrane.
slowly added to the solution with continuous agitation. 2.3 Formulation of mucoadhesive medicated liquid
Temperature of liquid suppository was maintained to 4°C suppositories
until a clear solution was obtained.
The medicated liquid suppository formulation was
Placebo liquid suppositories were evaluated for general optimized using Design expert, in whichMF9 was
characteristics, pH, gelation temperature, gel strength. optimized for preparation of mucoadhesive liquid
suppository. From among the nine medicated formulation,
Table 1. For mulation composition of placebo the MF9 demonstrating good gelling ability (+++),
(preliminary) batches of in situ gel. physiologically acceptable pH range in rectal delivery (pH
Name of ingredient -6.9), gellation temperature (36oC), gel strength (5mm)
F1 F2 F3 F4 F5
(% w/w) and prolong diffusion (In-vitro) over 5 hrs. To reinforce
Poloxamer 407 5 10 15 20 25 the gel strength and bioadhesive force of the liquid
Poloxamer 188 1 2 3 4 5 suppositories, the poloxamer solutions was added with
bioadhesive polymers. Medicated Gel was found to have
Aloe vera juice Q.S. Q.S. Q.S. Q.S. Q.S. weak mechanical strength. HPMC K4M, Carbopol 940
were selected as the bioadhesive polymer.
2.2.4 Formulation and evaluation of medicated liquid All six formulations of medicated mucoadhesive liquid
suppositories by using 32 factorial design [8] suppositories were evaluated for colour, clarity, pH,
Medicated liquid suppository was prepared by using gelation temperature, gel strength, drug content and drug
poloxamer 407 (5-25%) and poloxamer 188 (1-5%). release through dialyzing membrane. Selected formulation
Concentration of polymers was selected based on was evaluated for anti-haemorrhoidal activity.
evaluation of preliminary placebo suppository batches.
Design expert version 10.0.3.1 was used for factorial
design of formulation of liquid suppository. Poloxamer

© Published by DYPIPSR, Pimpri, Pune - 411 018 ( MH ) INDIA 43


2.4 Evaluation of liquid suppository
2.4.1 Physical Examination
Appearance of formulation, for this 5 ml of placebo
formulation was taken into clean and dry glass test tube
and was observed carefully for clarity and presence of
suspended particle if any against black and white
background.
Colour of formulation was visually observed.
2.4.2 pH of liquid suppository
The pH of suppository formulations was determined by
using digital pH meter. The pH meter was calibrated
before each use with standard phosphate buffer ( pH 7 and
4).
2.4.3 Gelation temperature [9]
Tube tilting method was used to determine gelation
temperature of placebo, medicated and mucoadhesive
liquid suppository. For this, 2 ml aliquot of liquid was
transferred to a test tube which was sealed with aluminium
foil, and test tube was placed in a water bath at 4°C. The
temperature of water bath was increased in increments of
1°C and left to equilibrate for 5 min at each new setting.
Gelation temperature was noted when the meniscus would
no longer move upon tilting of test tube through 90°.
2.4.4 Gel strength [10,11]
For this, 100ml glass measuring cylinder containing 50gm
of liquid suppository was placed in thermostat at 36.5°C
for gelation. For measuring gel strength apparatus
weighing 35gm was placed onto gelled suppository and
time required for the apparatus to move 5cm into the bulk
of gel was noted.
2.4.5 Mucoadhesive strength [12,13]
The mucoadhesive force of in situ gels liquid suppository
was determined on tissue specimen (A section of tissue cut
from the fundus of sheep rectum). The pieces of tissue
were stored in simulated fluid having pH 6.8. For
determination of mucoadhesive force, a section of tissue
was secured (keeping the mucosal side out) to the upper
Table 3. Composition medicated mucoadhesive Liquid suppositor y
Sr. Formulation Drug P 407
No code (%) (%)
1 MF9HP1 2 25
2 MF9HP2 2 25
3 MF9HP3 2 25
4 MF9CP1 2 25
5 MF9CP2 2 25
6 MF9CP3 2 25
© Published by DYPIPSR, Pimpri, Pune - 411 018 ( MH ) INDIA
Pharmaceutical Resonance 2018 Vol.1 - Issue 1
side of a glass vial using a using double sided adhesive
tape. The diameter of each exposed mucosal membrane
was 1.5 cm. The vials were equilibrated and maintained at
37° for 10 min. One vial with a section of tissue was
connected to the balance and the other vial was fixed on a
height adjustable pan. To the exposed surface of the tissue
attached on the vial, a constant amount of 0.1 g gel was
applied. The distance between two vials was adjusted in
such a way that the gel sample remained adhered to
mucosal membrane. Sufficient pressure was applied on
both of the vials for 10 seconds to allow proper adhesion
of gel to mucosa. A constant weight was added to the pan
(B) to the vial (C). The weight required for detaching the
two vials and hence, film of the sample between them was
noted down. The mucoadhesive force expressed as the
detachment stress in dyne/cm2, was determined from the
minimal weights needed to detach the tissues from the
surface of each formulation, using the following equation.
Where,
m : weight added to the balance (gm)
g : acceleration of gravity
A : area of the tissue exposed (πr2)
2.4.6 Dissolution studies (In vitro) pH 6.8Phosphate
buffer for lidocaine [13,14]
The in vitro drug release studies from medicated liquid
suppository and mucoadhesive liquid suppository was
monitored by using USP II dissolution apparatus. A 2g of
the formulation was placed in semi permeable bag and
secured with the aid of non absorbing thread. The bag was
immersed in a vessel containing dissolution medium, 500
ml phosphate buffer, pH 6.8 at 370C. The speed of rotation
was 100rpm. At predetermined time intervals 4 ml of
aliquots were withdrawn and analyzed spectro-
photometrically at 263 nm. The experiments were
conducted in triplicates.
HPMC
P 188 Carbopol Aloevera
K4M
(%) 940 (%) Juice
(%)
5 0.5 - QS
5 0.75 - QS
5 1.0 - QS
5 - 0.5 QS
5 - 1.0 QS
5 - 1.5 QS
44
 Pharmaceutical Resonance 2018 Vol.1 - Issue 1

2.4.7 In vivo animal study (Anti haemorrhoidal position of peaks of lidocaine.

activity) [15]
3.3 Characteristics of placebo liquid suppositories
To test the anti haemorrhoidal activity of optimized in situ
All placebo liquid suppositories were clear, colorless
gel liquid suppositories,male wistar rats weighing (200-
solution. There was no gelation and colour change of any
250gm) that were housed in standard conditions of
suppository during processing. pH of all the
temperature (22±3°C), relative humidity (55±5%), and
suppositories was found to be in range of 6.7-6.9
(12h light-dark cycle) before and during the study. Rats
respectively. The pH of placebo liquid suppository
were fed with standard pellet diet and water ad libitum.
solution was near to pH of rectum (6.7-6.9). Thus
Protocol for animal study was approved by the
therefore formulation will not produce irritation on
Institutional Animal Ethics Committee (IAEC) of Prado
instillation into the rectum.
preclinical research and development organization.
The liquid suppository should remain liquid at room
2.4.8 Procedure for induction of haemorrhoids temperature and should instantly form gel in rectum, so
the gelation temperature should be 30-36o C. Formulation
Four groups of male wistar rats (200-250gm) were
F1, F3, F5 showed gelation temperature in range of 30-36°
formed, each group having 8 rats. Croton oil preparation
C.Hence, this formulation concentration used for 32
containing deionized water, pyridine, diethylether, and 6%
factorial design of medicated liquid suppository. The
croton oil in diethylether(1:4:5:10)was used for induction
temperature-dependent gelation of poloxamer solutions
of haemorrhoids. After overnight fast, hemorrhoids were
could be explained by configuration change. Poloxamer
induced by inserting sterile cotton swabs (4 mm diameter)
molecules exhibit a well-arranged zigzag configuration.
soaked in 100 μL of croton oil preparation into the anus
With increasing temperature, the zigzag configuration of
(rectoanal portion, 20 mm from anal opening) of all group
poloxamer may be transformed into a close-packed
animals except normal control group. After 10 seconds
meander configuration, forming a more close-packed and
cotton swab was removed and animals were observed for
more viscous gel.
development of edema and blood in faces up to 8 hours
after induction of croton oil. Twenty-four hours after
induction of haemorrhoids, animals of respective groups
were treated for five days.G1-Distilled water, G2-positive
absorption

control, G3-test aloe vera suppository (once daily for 5

days), G4-test mixture suppository (once daily for 5 days).
On the fifth day, 1 hour after the treatment, all the animals
were sacrificed by deep isoflurane anesthesia and
rectoanal tissues (20mm in length) were isolated.
Rectoanal tissues were fixed in 10% neutral buffered
formalin solution for histological examination. The
inflammatory cells, congestion, haemorrhage, conc µg/ml
vasodilatation, and medium to high degrees of necrosis
were the histological observations for rectoanal tissue.
Results of the animal study were expressed as mean ±
SEM and analyzed by one-way ANOVA followed by
absorption

Dunnett’s post test using GraphPad Prism version 4.01.

3. Result and Discussion
3.1 Spectrophotometric characteristics of lidocaine
The UV spectrum (λ max) of lidocaine in water and pH
6.8 phosphate buffer indicated λmax at 263 nm. The
standard calibration curve of Lidocaine in distilled water
and phosphate buffer pH 6.8 was found to be linear over
conc µg/ml
the range of 2 -10 µg/ml as shown in Fig.1.
3.2 Drug-excipient compatibility study Fig. 1 Calibr ation cur ve of lidocaine in distilled water
and pH 6.8 phosphate buffer
FT-IR spectrum (Fig 2) of lidocaine showed major peaks
at 3030cm-1, 3248 cm-1, 1667 cm-1, 2860 cm-1, 2931 cm-1, 3.4 Characteristics of medicated liquid suppositories
3447 cm-1. FTIR spectrum of mixture of lidocaine and
excipients revealed that there was no interaction between All 9 formulations were prepared by following 32 full
drug and excipients, as there was no major change in the factorial designs. The formulations were evaluated for

© Published by DYPIPSR, Pimpri, Pune - 411 018 ( MH ) INDIA 45


physicochemical characterization and drug release study.
All formulations were clear, colourless solution. The pH
of medicated liquid suppository solution was nearing to
pH of rectum (6.7-6.9). Gelation temperature range for
liquid suppository should be 30-36o C. So that it will be a
liquid at room temperature and forms a gel instantly in the
rectum. Formulation MF2, MF5 and MF9 shown gelation
temperature between 30 to 36oC. Gel strength of all
formulation was found in the range of 6 to 45 sec. The gel
strength is an indication for viscosity of the gel at
physiological temperature. The data obtained indicates, as
the polymer grade variation increases gel strength.
Gel strength play important role in the development of
liquid suppository. Determination of gel strength allows
the easy insertion of the suppository and no leakage from
the anus. The contents of lidocaine in the medicated liquid
suppository range between 99-101% which is acceptable.
Formulation indicated comparable release profile over 5
hrs. Release of lidocaine is higher in first hrs, because it is
entered in sol form (Fig 3). Because thermo sensitivity
nature, formulation require few minutes to convert to gel
form. In the gel form retardation of release rate is less. The
probable mechanism in retardation of release may be
reduction in number and dimension of the channels in the
gel structure.
Fig.2: FTIR spectr um of lidocaine & physical mixtur e
of lidocaine and excipient
3.5 Full factorial design
Effect of formulation variables on gelation
temperature
On applying the factorial design, the quadratic model was
found to be significant with model F value of 33.00, p
value < 0.008 which implied that model was significant.
Following quadratic equation describes the effect of
concentration of polymers on gelation temperature.
Y1= 32.55 - 5.83X1 + 1.66X2 + 1.25 X1X2 + 4.16X12 +
1.66X22
© Published by DYPIPSR, Pimpri, Pune - 411 018 ( MH ) INDIA
Pharmaceutical Resonance 2018 Vol.1 - Issue 1
There was significant (p<0.008) effect of individual
variable on gelation temperature. The gelation temperature
decreases with increase in concentration of Poloxamer 407
(X1). At low level of factor X1 gelation temperature is
high and at medium level gelation temperature is about
36oC. The gelation temperature increases with
concentration of factor poloxamer 188(X2), but as not
rapid as X1. The combined effect of factor X1 (poloxamer
407) and X2(Poloxamer 188) can be further elucidated
with help of response surface plot (figure). At high level
of X1 and X2 the gelation temperature was 36oC.
Fig 3: Dissolution plots of cumulative dr ug r elease of
lidocaine liquid suppository of above formulation
Table 4. Summar y of ANOVA for gelation
temperature parameters
Degree
Sum of Mean F p-value
Source of
Squares Square value Prob>F
freedom
0.008
Model 267.3 5 53.47 33.00
(S)
Residual 4.86 3 1.62 - -
Total 272.22 8 36.44 - -
3.6 Contour plot and three dimensional response
surface plot of Gelation temperature
Two-dimensional contour plot and three dimensional
response surface plot is shown in Fig 4A and 4B
respectively. The contour plot does not show straight line,
it indicates that there is no linear relationship between the
factor X1 and X2. The gelation temperature decreases
with increase in concentration of Poloxamer 407 (X1). At
low level of factor X1 gelation temperature is high and at
medium level gelation temperature is about 36o C. The
gelation temperature increases with concentration of factor
X2, but as not rapid as X1. The combined effect of factor
X1 (poloxamer 407) and X2(Poloxamer 188) can be
further elucidated with help of response surface plot
(figure). At high level of X1 and X2 the gelation
temperature was 36oC.
46
 Pharmaceutical Resonance 2018 Vol.1 - Issue 1

Effect of formulation variables on drug release Poloxamer 407 (X1) drug release is high. The drug release
increases with concentration of factor X2 , but as not rapid
On applying the factorial design, the quadratic model was
as X1. The combined effect of factor X1 (poloxamer 407)
found to be significant with model F value of 5.63, p
and X2(Poloxamer 188) can be further elucidated with
value < 0.0465 which implied that model was significant.
help of response surface plot (figure). At high level of X1
Following quadratic equation describes the drug release.
and X2 the drug release was maximum.
Y2= 86.39- 2.34X1 +0.74X2 +6.90 X1X2
The quadratic model was found to be significant with F Table 5. Summar y of ANOVA for Dr ug r elease
value 5.63 (p<0.046) that indicates that the model is parameters
significant. Positive sign in the above equation indicates
that response increases with the factor. Negative sign Degree
Sum of Mean F p-value
Source of
indicates negative effect on drug release, response does Squares Square value Prob>F
freedom
not increase with factor. 0.0465
Model 227.6 3 75.75 5.63
sign-Expert® Software
(S)
ctor Coding: Actual Gelat temp
lat temp
Design Points
45
1
Residual 67.30 5 13.46 - -
30

= A: A 0.5
Total 294.56 8 86.39 - -
B: Conc. of poloxamer 188

= B: B

35
40 Design-Expert® Software
0
Factor Coding: Actual Invitro
Invitro 1
Design Points 90
94.28
85
30
76.75
-0.5
X1 = A: A 0.5
B: conc. of poloxamer 188

X2 = B: B

-1
-1 -0.5 0 0.5 1
0

A: conc. of Poloxamer 407 85

Fig. 4 a 90
-0.5
Design-Expert® Software
Factor Coding: Actual
Gelat temp
Design points above predicted value 80
Design points below predicted value
45

30 45 -1
X1 = A: A 40 -1 -0.5 0 0.5 1
X2 = B: B
Gelat temp

35

30 A: conc. of poloxamer 407

25

1
Fig. 5 a
Design-Expert® Software
Factor Coding: Actual
0.5 Invitro
Design points above predicted value
Design points below predicted value
94.28
0
1 76.75
B: Conc. of poloxamer 188 95
0.5 X1 = A: A 90
-0.5 X2 = B: B
0
85
Invitro

-0.5 80
-1 -1 75
A: conc. of Poloxamer 407
1

Fig. 4 b 0.5

Fig 4 a: Contour plot showing combined effect of B: conc. of poloxamer 188

0

Poloxamer 407 and Poloxamer 188 on Gelling -0.5

0
0.5

temperature. -1 -1
-0.5

A: conc. of poloxamer 407

Fig 4 b: Response sur face plot showing combined effect
of Poloxamer 407 and Poloxamer 188 on Gelling Fig. 5 b
temperature.
Fig 5 a: Contour plot showing combined effect of
Fig 5A and 5B indicate two-dimensional contour plot and Poloxamer 407 and Poloxamer 188 on drug release
three dimensional response surface plot respectively. The Fig 5 b: Response sur face plot showing combined effect
contour plot does not show straight line, it indicates that of Poloxamer 407 and Poloxamer 188 on drug release
there is no linear relationship between the factor X1 and
X2. The percentage release increases with increase in
concentration of Poloxamer 407 (X1). At low and medium
level of factor X1 drug release is less and high level

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 Pharmaceutical Resonance 2018 Vol.1 - Issue 1

Table 6. Result of exper iments for confir ming optimization capability

X1 conc. of poloxamer X2 conc. of poloxamer Response (Y1) Response (Y1)

Batch
407 188 Gelation temperature Gelation temperature
Actual value - 36oC Actual value - 92.41 %
MF9 25% 5%
Predicted value - 35.47oC Predicted value - 91.61%
% error - - 1.47% 1.08%

3.7 Characteristics of medicated mucoadhesive mucoadhesive polymer decreases gelation temperature.

liquid suppositories: HPMC K4M has less effect on gelation temperature as
compared to Carbopol 940. Mucoadhesive polymer
The medicated liquid suppository formulation was
decreases gelation temperature of thermosensitive in situ
optimized using Design expert, in which MF9 containing
gel containing poloxamers, due to their ability to bind to
25% poloxamer 407 and 5% poloxamer 188 was
the polyoxyethylene chain present in the poloxamer
optimized for preparation of mucoadhesive liquid
molecule. This promotes dehydration causing increasing
suppository. To increase the gel strength and bioadhesive
inter molecular bonding which leads to gelation at lower
force of the liquid suppositories, bioadhesive polymers
temperature. As concentration of bioadhesive polymer
were added in optimized medicated liquid suppository.
increases gel strength also increases.
Medicated liquid suppository gel was found to have weak
Formulations containing carbopol 940 shows more gel
mechanical strength. HPMCK4M, Carbopol 940 were
strength as compare to formulations containing HPMC
selected as the bioadhesive polymer. These bioadhesive
K4M. There was increase in bio-adhesive strength with
polymers are water-soluble or swellable, but different in
increase in concentration. Mucoadhesive force means the
their nature and charges. HPMC a cellulose derivative is
force with which liquid suppository binds to mucosal
neutral and swelling in water. Carbopol940, a polyacrylic
membrane. Poloxamer gels without addition of
acid derivative polymerized without cross-linking agent, is
mucoadhesive agent had less mucoadhesive force. HPMC
anionic and water-swellable. Gelation temperature range
K4M and Carbopol 940 mucoadhesive strength increases
for liquid suppository should be 30-36°C. This allows it to
with concentration. But carbopol 940 have effect on
remain liquid at room temperature and gel formation in the
gelation temperature with increase in concentration.
rectum instantly. Increase in concentration of

Table 7. Char acter istics of mucoadhesive medicated liquid suppositor y

Gelation Cumulative Mucoadhesive strength

Sr. No. Formulation code Gel strength
temperature (oC) drug release (dyne/cm2)
1 MF9HP1 36.75±0.375 15.66±0.57 90.73±0.27 5748
2 MF9HP2 34.45±0.102 14.36±0.471 91.37±0.38 5992
3 MF9HP3 30.98±0.896 14.57±0.467 83.75±0.48 6998
4 MF9CP1 33.02±0.368 16.33±0.57 82.64±0.47 5717
5 MF9CP2 29.67±0.896 17.0±1.0 81.59±0.34 6338
6 MF9CP3 28.09±0.367 17.6±0.57 78.89±0.62 6660

Fig 6: Dissolution plots of cumulative dr ug r elease of lidocaine mucoadhesive liquid suppositor y

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 Pharmaceutical Resonance 2018 Vol.1 - Issue 1

3.7.1 In vitro drug release study of mucoadhesive
liquid suppository
Drug release was retarded by the addition of
mucoadhesive polymers. Formulations containing HPMC
K4M showed more than 82% drug release in 5 hrs while
formulations containing carbopol 940 showed less than
80.40% drug release in 5 hrs. The retarding effect of the
carbopol 940 could be attributed to high viscosity.
Formulation MF9HP2 was selected for further study as
drug release was found to be 91.37% at the end of 5hrs
(Fig 6).
be most effective in imparting stability of formulation by
maintaining gelation temperature 30-36oC. The selected
formulation exhibited relevant drug release (in vitro). This
formulation exhibited the optimal Gelation temperature,
gelling ability, gelling time, pH, gel strength, viscosity, %
drug content, mucoadhesive strength, reduce
inflammation in croton oil-induced rats to qualify as
rectal drug delivery system for treatment of hemorrhoids.
The (MF9HP2) formulation has been successfully
formulated to offer stable, cost effective and safe delivery
system for treatment of hemorrhoids.

3.7.2 In vivo animal study

A. Normal rectoanal region : Fig A shows nor mal
architecture of recto anal region. In normal rectoanal
region mucosal layer, submucosal layer and blood
vessels are intact. A
B. Haemorrhoids induced rectoanal region (Possitive
control) : The sections of r ectoanal r egion showing
severe infiltration of inflammatory cells in mucosa as
well as submucosa of colon (Arrow). Marked to
severe inflammation, congestion, haemorrhage,
dilatation of blood vessels, degeneration, and necrosis
can be observed in the section of untreated positive
control group
C. Haemorrhoids induced recto anal region treated B
with aloe vera juice in situ gel suppository: The
sections of recto anal region showing minimal
infiltration of inflammatory cells of recto anal region.
Mild inflammation, marked congestion, degeneration,
and necrosis.
D. Haemorrhoids induced recto anal region treated
with aloe vera juice+ lidocaine in situ gel
suppository: Minimal infiltr ation of inflammator y
cells (arrow) and degeneration of lining mucosa. C

From the above findings of the study (Fig 7), it can be

concluded that after five days of treatment of prepared in
situ gel liquid suppositories containing (Lidocaine) and
aloe vera juice as a vehicle liquid suppositories (Fig.7d)
has shown near normal architecture. In situ gel liquid
suppository containing aloe vera juice has shown mild
inflammation, marked congestion, degeneration, and
necrosis. Though aloe vera juice liquid suppository has not D
shown normal architecture, it is indicating positive sign
towards cure of hemorrhoids. After treatment with Aloe
vera juice-liquid suppository and combination of lidocaine
+ aloe vera juice liquid suppository shows significant
reduction in the inflammation of croton oil-induced Fig 7: Histopathology of mucosal layer of r ecto anal
hemorrhoids in rats compared to positive control. This region treated with final formulation in hemorrhoids
may be due to the potent anti-inflammatory activity of the induced rats
herbs present in the tested formulation.
4. Conclusion
Liquid suppository of lidocaine MF9HP2 containing
poloxamer 407, poloxamer 188 and HPMC K4M found to

© Published by DYPIPSR, Pimpri, Pune - 411 018 ( MH ) INDIA 49


Acknowledgments
The authors are grateful to JSPM’s Jayawantrao
Sawant College of pharmacy and research, Hadapsar,
Pune for supplying of all the basic requirements of this
research.
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