Formulation, Development and

Evaluation of Ciprofloxacin
Hydrochloride Soft Gel for Oral
Administration

About Author: Alka Lohani

M.Pharm (Pharmaceutics)
department of pharmaceutical sciences bhimtal campus
kumaun university nainital
Abstract:
Inconvenience of administration and patient compliance are gaining significant importance
in the design of dosage forms. Difficulty in swallowing (dysphagia) is common among all age
groups, especially in elderly and pediatrics. Ciprofloxacin hydrochloride is an orally
administered antibacterial agent. The objective of this study was to develop ciprofloxacin
hydrochloride soft gel using sodium alginate as a gelling agent and sodium citrate as a
source of cation. Gels are formed by aggregation of polymers with minimum two
components; the gelling agent and the fluid component. Different batches were prepared
using three different concentrations of sodium alginate (0.1, 0.4, and 0.8%). The
consistency of sodium alginate gel was dependent on the concentration of, sodium alginate,
sodium citrate and co-solute. The results of dissolution study of soft gel F3 containing 0.4%
sodium alginate and 0.3% sodium citrate revealed that Ciprofloxacin hydrochloride was 85%
released in 45 min. and possessed acceptable sensory characteristics when evaluated by
human volunteers. Short term stability study carried out for four weeks at different
temperatures (0C and room temperature) showed no considerable changes in performance
characteristics of developed optimized formulation.
Introduction:
Recently, more stress is laid down on the development of organoleptically elegant and
patient friendly drug delivery system for pediatric and geriatric patients.1, 2 Many patients,
elders and person with dysphagia find it difficult to swallow the tablets and hard gelatin

capsules which results in high incidence of noncompliance and ineffective therapy. The
patients with dysphagia can be choked by water while consuming liquid formulation which
can be eliminated by administering liquid formulations with high viscosity.3, 4, The gel dosage
form can be swallowed easily without water and are soft and smooth. The objective of this
investigation was to develop hydrophilic gel dosage form for oral administration of
Ciprofloxacin. Ciprofloxacin hydrochloride is a broad-spectrum fluoroquinolone antibacterial
agent is more absorbed from the stomach and the proximal part of the small intestine. 5
Materials and MethodsCiprofloxacin was obtained as gift sample from Finecure (P Ltd.)U. S. Nagar. Uttrakhand,
Sodium alginate, Methyl paraben, propyl paraben, and all other chemicals like citric acid,
sodium citrate, mannitol, purchased were of analytical grade.
Preparation of oral soft gelAll the required ingredients of the formulation were weighed accurately. Sodium alginate
powder was dispersed in 50 ml of distilled water maintained at 95C. The dispersion was
stirred at 95C for 20 min using a magnetic stirrer. Ciprofloxacin was added with stirring.
Then sucrose, citric acid, and preservatives (methylparaben, propylparaben) were added
with stirring. Finally, required amount of sodium citrate was dissolved in 10 ml of distilled
water and added to the mixture. The weight of the gel was monitored continuously during
manufacturing and finally it was adjusted to the 100 gm with distilled water. The mixture
was allowed to cool to room temperature to form gel. The mixture containing Sodium
alginate, ciprofloxacin, and other additives was packed in polyethylene bag with airtight
seal. The gels were prepared using three different concentrations of sodium alginate (0.1,
0.4, and 0.8%), each with two different sodium citrate concentrations (0.3 and 0.6%). The
composition of Ciprofloxacin soft gel is shown in table-1.

INGREDIENT

F1

F2

F3

F4

F5

F6

Ciprofloxacin%

2.5

2.5

2.5

2.5

2.5

2.5

Sodium alginate%

0.1

0.1

0.4

0.4

0.8

0.8

PEG 400%

10

10

10

10

10

10

Citric acid %

0.05

0.05

0.05

0.05

0.05

0.05

Sucrose %

66

66

66

66

66

66

Evaluation of oral soft

gel
The ciprofloxacin soft gels
were examined for
appearance in terms of
clarity, texture and
consistency. Ciprofloxacin
soft gels were also
evaluated for viscosity, pH,
and drug content and in

Sucralose %

0.3

0.3

0.3

0.3

0.3

0.3

vitrodrug release. Texture

Sodium citrate %

0.3

0.6

0.3

0.6

0.3

0.6

evaluationTexture of the

Methylparaben (mg)

0.18

0.18

0.18

0.18

0.18

0.18

Propylparaben (mg)

0.02

0.02

0.02

0.02

0.02

0.02

Raspberry flavor %

Water %, up to

100

100

100

100

100

100

soft gel was evaluated in

terms of stickiness and
grittiness by mildly rubbing
the gel between two
fingers.
Rheological
measurement-Viscosity
of the all the batches of soft gels was measured using Brookfield DV-II+Pro viscometer. The
Ciprofloxacin soft gel was squeezed out from the polyethylene plastic bag by making a cut of
uniform size on the bag and viscosity was measured using spindle number LV4 at the
rotation of 50 rpm at room temperature. The viscosity measurements were made in
triplicate using fresh samples each time. Results are shown in table 2.
Table-2, showing
Parameters

F1

F2

F3

F4

F5

Viscosity(cP

18623

25525

71508

75629

1015210 1218213

s)

pH

6.93

6.08

6.99

6.12

6.05

6.10

F6

viscosity and pH
pH of the soft gel
The pH of the final
gel has got influence
on stability, and on
the taste. The pH of

ciprofloxacin soft gel was measured by using Digital pH meter at room temperature. Results
are shown in table 2.
Drug content Drug content of the ciprofloxacin soft gel was estimated by eluting the drug
from 10g of gel in phosphate buffer pH 6.8. The drug content was estimated by UVspectrophotometer at 278 nm after filtering the sample through whattman filter paper.
Taste evaluation- Ten healthy, adult human volunteers participated in taste evaluation of
ciprofloxacin soft gel (F3). One dose of the ciprofloxacin soft gel (10 g) containing 250 mg
of ciprofloxacin was given to every volunteer and they were told to keep the gel in mouth
for 5 sec. The volunteers were instructed not to swallow the gel. The volunteers were asked
to comment on the bitterness, aftertaste, sweetness and flavor of the gel. Mouth feel in
terms of grittiness was also checked. The results of taste evaluation of ciprofloxacin soft gel
are shown in table-3
Table -3, Taste evaluation (formulation F3)
Parameters 1

10

Bitterness

NB

NB

NB

NB

NB

NB

NB

NB

NB

NB

Aftertaste

NB

NB

NB

NB

BT

NB

NB

NB

NB

NB

Sweetness

VS

SW

VS

VS

VS

VS

VS

VS

VS

SW

Flavor

GD

GD

GD

GD

GD

GD

GD

GD

GD

GD

Mouth feel

GD

GD

GD

GD

MD

GD

GD

MD

GD

MD

NB- non-bitter, BT-bitter, SW-sweet, VS- very sweet, GD-good, MD-moderate

In vitro drug release6- In vitro drug release studies was carried out using USP dissolution
apparatus 2 using paddle at a speed of 100 rpm using 900 ml of pH 6.8 phosphate buffer as
dissolution media at 372C. Soft gel (5 gm) containing 250 mg of ciprofloxacin was used
in the dissolution test. Sample was withdrawn at the interval of every five minutes and the
drug solution was replaced with the same volume of phosphate buffer (pH 6.8) maintained
at 372C. Absorbance was measured at 278 nm using UV- Spectrophotometer after
suitable dilution of the samples.
Stability studies of soft gel- Thesamples were kept at different temperatures (0-8,
255, 452) for four weeks. The samples were observed for pH, viscosity and

appearance at the interval of 2 week. The results of the stability studies are shown in table4
Table-4 stability studies of ciprofloxacin soft gel (Formulation F3)
Temperature

0C

Room Temperature*

weeks

pH

6.91

6.89

6.99

6.92

Viscosity(cPs)

7150

7168

7162

7169

*about 28C
Results and DiscussionAll the batches of soft gels were transparent in appearance. The gel of formulation F1, F2,
and F3 were non-sticky and non-gritty while the gel of formulation F4 was slightly sticky but
non gritty. The non-gritty nature of the formulation F5 to may be due to the suitable
concentration of sodium alginate and sodium citrate but F6 was gritty due to higher
concentration of both sodium alginate and sodium citrate.
The gel of formulation F1 and F2 exhibited fluid like consistency while the gel of formulation
F5 and F6 were very thick in consistency.
Viscosity is the one important parameter which provides vital information during the
optimization of the soft gel. The viscosity of the formulation F1 and F2 were low because of
its fluid like consistency while the viscosity of the formulation F5 and F6 were high because
they were very thick in consistency. As formulation F5 and F6 were thick in consistency,
sticky and gritty, they failed to give good mouth feel. The viscosity of the formulation F3 and
F4 were acceptable. The consistency and viscosity of the soft gels are related to each other
because both are dependent on concentration of sodium alginate, sodium citrate, and cosolute. Effect of concentration of co-solutes (sucrose and sucralose) on the viscosity and
consistency of all the batches of the soft gel was same because the co-solutes were used at
same level in all the batches. formulation F3 consisting of 0.4% sodium alginate and 0.3%
sodium citrate was considered as an optimum batch considering viscosity and appearance.
The pH of the maximum stability of ciprofloxacin in aqueous phase is in between 1.5 to 7.
Therefore, the pH of the formulated gels was adjusted and maintained in between 5 to 7
with help of buffering agents such as citric acid and sodium citrate. Sucrose may crystallize

in presence of citric acid on standing.[8] Therefore, the amount of citric acid was kept
minimum, just to adjust to the required pH. Sodium citrate was selected as a salt to
contribute cation because it also act as sequestrant, buffering agent and helps in
maintaining mechanical property of the gel.7 The drug content of the formulations F3 and F4
were 99.61.56% and 99.11.48%, respectively which is well within the acceptable limit.
The results shown reveal that gels of the formulation F3 exhibited acceptable consistency
and viscosity. Thus, it was subjected to dissolution study. Dissolution studies of the
ciprofloxacin soft gel containing 0.3% of sodium alginate and 0.3% of sodium citrate
showed 85% release of the drug within 45 min.
The results of taste evaluation of the formulation F3 ciprofloxacin gel are shown in Table 3.
All the ten volunteers perceived the soft gel as non-bitter. Addition of flavors and
sweeteners is the foremost and simplest approach for taste masking especially in the case
of pediatric formulations. Sucrose (66%) was not able to mask the bitter taste completely
because sugar molecules might have been trapped into the gel network. Sucralose was
selected as an auxiliary sweetener because it is non-carcinogenic and 300-1000 times
sweeter than the sucrose.8 Raspberry flavor was selected because to certain extent it helps
in masking the bitter taste of drug and also improves patient acceptance.
The results of stability studies, shown in Table 4 indicate no considerable changes in pH,
viscosity and appearance of the formulations. Precipitation of ciprofloxacin in the soft gels
was not observed