Original/Brief

Formulation and evaluation of transparent

ibuprofen soft gelatin capsule
A. Lodha, A. Patel, J. Chaudhuri, P. Jadia, T. Joshi, J. Dalal

Gujarat Liqui Pharmacaps ABSTRACT

Pvt. Ltd. 662-666, GIDC,
The compound ibuprofen, 2-(4-isobutylphenyl) propionic acid, has been known e.g. from Martindale, the Extra
Waghodia, Baroda,
Gujarart, India
Pharmacopoeia, 28th edition, 1982, p.256, as a drug which had anti-inflammatory and analgesic properties. It is
used for the treatment of rheumatoid arthritis or other inflammatory diseases of joints, soft tissue rheumatism
Address for correspondence: and gout. Ibuprofen, because of its analgesic properties, has been widely used as anodyne, e.g. against pain
Lodha Ami, or discomfort associated with headache, toothache or menstruation.
E-mail: ami.m.sha@gmail.
A medication suitable to combat acute pain is demanded to display its effects fast which action, in turn, is only
com
achieved by a quick release and good bio-availability of the active-ingredient. It is for the commercial forms
in particular that the conditions of preparation must be strictly observed, as minor alterations in production
procedures such as mixing, pressure of compression and type of machine will affect the physical properties of
the particles of he active ingredient and will deteriorate its bio-availability. It is an object of this presentation
to provide a medicament that can be readily taken that contains an active amount of ibuprofen in a carrier,
that is simple to prepare and that will quickly display a high activity.

KEY WORDS: Ibuprofen, anti-inflammatory

Formulation development 300) in the fill formulations is limited due to their ability to
diffuse into the shell and thereby act as gelatin plasticizers. The
Vehicle extent of diffusion of a polyethylene glycol from the fill into the
shell decreases with an increase in its molecular weight. Orally

C ompound that show low aqueous bio-availability have the

tendency to precipitate when small amounts of water is
added to the solution, thus affecting its resorption. This can
be overcome by the addition of combination of Hydrophilic
vehicles. Hydrophilic vehicles for softgel fill formulations
include polyethylene glycols (e.g., PEG 400, PEG 600),
polyoxyethylene – polyoxypropylene copolymers (Poloxamers),
propylene glycol, glycerin, ethyl alcohol, and water. The use of
propylene glycol, glycerin, and water is restricted to less than
10% of the total fill formulation, as these vehicles can also
act as plasticizers for the gelatin shell. Similarly, use of lower
molecular weight polyethylene glycols (e.g., PEG 200, PEG
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DOI:
10.4103/0975-7406.94154
administered polyethylene glycols of a lower molecular weight
(e.g., PEG 200, PEG 300, PEG 400) are well absorbed in the
GIT and are mostly (>90%) excreted unchanged in urine and
feces in human subjects.
Solubility enhancers
It is desirable to produce a highly concentrated solution of a
compound as it allows the encapsulation of a unit dose of the
compound in a softgel that is small enough to swallow easily
and thus improving patient acceptance of the medication.
The solubility of the acidic compounds like ibuprofen can be
enhanced in polyethylene glycols by 40–400% through partial
ionization of this compound with a hydroxide ion species
(e.g., sodium hydroxide, potassium hydroxide, ammonium
hydroxide). When this neutralization (counter ion) technique
is used to obtain a highly concentrated solution of a compound,
it is essential to keep the apparent pH of the final fill
formulation at least between 2.5 and 7.5. At pH values below
2.5, gelatin is hydrolyzed causing leakage of the softgel, whereas
at pH values above 7.5, gelatin may be either hydrolyzed or

How to cite this article: Lodha A, Patel A, Chaudhuri J, Jadia P, Joshi T, Dalal J. Formulation and evaluation of transparent ibuprofen soft gelatin capsule. J
Pharm Bioall Sci 2012;4:95-7.

Journal of Pharmacy and Bioallied Sciences March 2012 Supplement S95 

 Patel et al.: Formulation, process development and evaluation of artemether and lumefantrine soft gelatin capsule
tanned (i.e. cross-linked) resulting in decreased solubility of
the gelatin shell.
Alternately, the solubility of ibuprofen in hydrophilic
vehicles can also be improved significantly by using povidone
(polyvinylpyrrolidone, PVP) as a solubility enhancer. Unlike the
solubility enhancing techniques employed the use of povidone
as a solubility enhancer results in a softgel fill formulation
containing a compound in its original form that is very
compatible with the other softgel components. In addition, as
povidone is available in a variety of molecular weights ranging
from 2500 to 3000000 the viscosity of a fill formulation can
be controlled through the selection of appropriate molecular
weight and concentration of the polymer without adversely
affecting the solubility of dissolved compounds.
Materials and Methods
Ibuprofen (active ingredient), polyethylene glycol 400
(vehicle), polyvinyl pyrrolidone (K-10) (solubility enhancer),
polyethylene glycol (co-solvent), potassium hydroxide
(ionizing agent).
Optimization of fill material
In order to obtain the optimized fill formulation, ibuprofen is
initially dissolved in 15 to 50 parts of polyethylene glycol along
with 2 to 50 parts of polyethylene glycol which is then mixed
with polyvinyl pyrrolidone K-30. The previously mixed potassium
hydroxide with water is added till optimum pH is obtained.
Encapsulation parameter
Evaluation of ibuprofen soft gelatin capsules
Uniformity of fill weight of the capsules
Weigh an intact capsule. Open it without losing any part of the
shell and remove the contents as completely as possible. Wash
the shell with a suitable solvent and keep aside until the odor of
the solvent is not perceptible. Weigh the shell. The difference
between the weighing gives the weight of the contents. Repeat
 S96 Journal of Pharmacy and Bioallied Sciences March 2012 Supplement
the procedure with another 19 capsules. The weight complies
as per the pharmacopoeial limits.
Loss on drying of the capsule shell
Soft gelatin capsule shells normally contain 6% to 13% of water
and the Loss on Drying of the shell was found to be within the
limit.
Disintegration test for soft gelatin capsules
Although there are no official limits specified, ideally a
disintegration time within 30 minutes is considered ideal for soft
gelatin capsules. The formulated capsules disintegrated within
a maximum of about 25 mins as shown in the table.
Dissolution studies of ibuprofen soft gelatin
Ideal media for dissolution study was optimized from the
disintegration test prior to dissolution testing studies. Various
Gastric stimulated media for dissolution were 0.1N HCl (pH 1-2),
acetate buffer (pH 4.5), phosphate buffer (pH 7.8) and water.
The dissolution media consisting of Phosphate Buffer Solution at
pH 7.8 provided best cumulative drug release as depicted in
graphs.
Assay
Experimental chromatographic conditions
Stationary phase: Phenomex, 5 µm, C18 (250x4.6 mm) column
Mobile phase: A mixture of 3 volumes of orthophosphoric acid,
247 volumes of water and 750 volumes of methanol
Detection wavelength: 264 nm
Flow rate: 1.5 ml/minute
Operating pressure: 160 kgf
Temperature: Room temperature.
Preparation of standard solution:
100 mg of Ibuprofen diluted with the Mobile phase up to 100 ml
(Stock Solution).
Make 100 µg/ml of Ibuprofen diluted with the Mobile phase.
Aliquots of standard solutions containing 40  µg/ml of
Ibuprofen.
Preparation of sample solution:
20 tablets → Average weight → Powdered and weighed a
quantity equivalent to 100 mg of Ibuprofen were transferred
to 100 ml standard flask and make up with mobile phase. Filter
with Whatman filter paper.
 Patel et al.: Formulation, process development and evaluation of artemether and lumefantrine soft gelatin capsule 

Figure 2: Comparative dissolution studies of developed formula and

Figure 1: Optimization of dissolution media marketed product

Aliquots of solution containing 40µg/ml diluted with mobile by employing the above mentioned techniques, a high-
phase. bioavailability is achieved with a high degree of reliability
and reproducibility and hence, a fast and reliable display of
Analysis of formulation its effects.

*RSD of six observations
Conclusion
The soft gelatin dosage form has an advantage over all other
previously known dosage form for ibuprofen that upon
intake the active ingredient is quickly resorbed. Nevertheless,
References
1. Brox W. 1988. Soft gelatin capsules and methods for their production.
US Patent 4,744,988.
2. Brox W. 1988. Gelatin capsule. US Patent 4,780,316.
3. Nazzal S, Wang Y. 2001. Characterization of soft gelatin capsules by
thermal analysis. Int J Pharm 230:35–45.
4. Dhabhar DJ. 1996. Process for reducing the precipitation of difficulty
soluble pharmaceutical actives US Patent 5,484,606.
Source of Support: Nil, Conflict of Interest: None declared.

Journal of Pharmacy and Bioallied Sciences March 2012 Supplement S97 

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