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Sudhamani T. et al. / International Journal of Biopharmaceutics. 2010; 1(2): 75-81.

IJB
International Journal of Biopharmaceutics

Journal homepage: www.ijbonline.com

FORMULATION AND EVALUATION OF IBUPROFEN


LOADED MALTODEXTRIN BASED PRONIOSOME
T. Sudhamani*, V. Ganesan, N. Priyadarsini, M. Radhakrishnan
The Erode College of Pharmacy, Erode, Tamil Nadu.

ABSTRACT
Ibuprofen loaded maltodextrin based proniosome were prepared by slurry method with different surfactant to carrier ratio.
The proniosome formulation was evaluated for FT-IR study and scanning electron microscopy. The niosomal dispersion was further
evaluated for entrapment efficiency, in-vitro release study, kinetic data analysis, stability study. The result from SEM analysis has
showed smooth surface of proniosome. The formulation F4 which showed higher entrapment efficiency of 96.57± 1.08% and in-
vitro cumulative drug release of 92.16% at the end of 12 hr was found to be best among the all 9 formulations. Release was best
explained by the zero order kinetics. Kinetic analysis showed that the drug release follows non-fickian release. Proniosome
formulation has showed appropriate stability for 60 days by storing the formulations at different conditions.

KEYWORDS: Ibuprofen, Proniosomes, Maltodextrin.

INTRODUCTION
This dry, free-flowing, granular product which,
Proniosomes are dry product which could be upon addition of water, disperses or dissolves to form a
hydrated immediately before use would avoid many of the multilamellar niosome suspension suitable for administration
problems associated with aqueous niosome dispersions and by oral or other routes.
problems of physical stability (aggregation, fusion, leaking)
could be minimized (Rhodes D G et al,1999). These dry Ibuprofen is considered to be the first-line drug in
formulations of surfactant-coated carrier can be measured out the symptomatic treatment of rheumatoid arthritis,
as needed and rehydrated by brief agitation in hot water ( osteoarthritis and ankylosing spondylitis. The successful
Almira, I et al 2001 ). They are water-soluble carrier particles treatment of arthritis depends on the maintenance of effective
that are coated with surfactant and can be hydrated to form drug concentration level in the body, for which a constant
niosomal dispersion immediately before use on brief and uniform supply of drug is desired. The short biological
agitation in hot aqueous media. Reported methods for half-life (about 2 hr) and dosing frequency more than once a
preparation of proniosomes were the spraying of surfactant day as well as two third (70-80%) of dose is excreted by renal
on water-soluble carrier particles and the slurry method transport. Therefore, an alternative non-invasive mode of
(Almira, I et al 2001). delivery of the drug is needed. Transdermal delivery certainly
*
appears to be an attractive route of administration to maintain
Corresponding author the drug blood levels of ibuprofen for an extended period of
time. The present study involves formulation of a topical
T. Sudhamani
ibuprofen gel from malltodextrin based proniosome.
E-mail: tsmkrishv28@yahoo.com
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Sudhamani T. et al. / International Journal of Biopharmaceutics. 2010; 1(2): 75-81.

MATERIALS AND METHODS Cf is the concentration of free drug.

Ibuprofen obtained as a gift sample from Swasan IN VITRO DRUG RELEASE STUDIES OF THE GELS
pharmaceuticals, India. Maltodextrin, Cholesterol, HPMC In vitro release studies were carried out using dialysis
and span-60 were purchased from Loba Chem. Pvt. Ltd., membrane employing in two sides open ended cylinder.1 ml
Mumbai. All other reagents used were of analytical grade. of proniosomal gel was placed uniformly in the dialysis
membrane previously soaked overnight. The two sides open
PREPARATION OF PRONIOSOMES ended cylinder was placed in the beaker containing 200ml of
phosphate buffer saline pH 7.4. Aliquots of 5 ml were
Proniosome were prepared by the slurry method withdrawn periodically and replaced with same amount of
(Mahmoud Mokhtar et al 2008, Fang JY et al, 2001). phosphate buffer saline solution to maintain the sink
Different ratios of formulations were prepared and dissolved condition. The samples were analysed by UV
in chloroform: ethanol (2:1) solution (Table 1). It was then spectrophotometrically at a λ max of 257 nm (Unchegbu, I.F
added to a 100ml round bottom flask containing the et al 1996, Yanhong Yang et al, 2002).
maltodextrin carrier. Additional chloroform: ethanol solution
was added to form slurry in the case of lower surfactant DRUG RELEASE KINETIC DATA ANALYSIS
loading. The flask was attached to a rotary flash evaporator to
evaporate solvent at 60 to 70 rpm, a temperature of 45 ± 2ºC, The release data obtained from various formulations
and a reduced pressure of 600mmHg until the mass in the were studied further for their fitness of data in different
flask had become a dry, free flowing product. These kinetic models like Zero order, Higuchi’s and peppa’s
materials were further dried overnight in a dessicator under (Korsmeyer R.W et al, 1983, Huguchi.T e al, 1963).
vacuum at room temperature. This dry preparation was
referred to as ‘proniosomes’ and was used for preparations SCANNING ELECTRON MICROSCOPY
and for further study on powder properties. These
proniosomes were stored in a tightly closed container at Proniosome powders were affixed to double-sided
refrigerator temperature until further evaluated. carbon tape, positioned on an aluminium stub and excess
powder was removed. The stubs were stored under vacuum
PREPARATION OF PRONIOSOMAL GEL BY USING overnight. The samples were sputter-coated with gold.
HPMC POLYMER Electron micrographs were obtained using scanning electron
microscope. The surface morphology (roundness,
The proniosomal powder was dispersed in HPMC smoothness, and formation of aggregates) of proniosomes
polymer solutions (2%) with stirring at 100 rpm, for 1 hour was studied by Scanning Electron Microscopy (Alsarra, I A
using magnetic stirrer. This was further neutralized with
et al, 2005).
0.5% triethanolamine amine and 10% glycerine slowly with
constant stirring. This proniosomal gel was taken for further
studies (Chandra et al 2008, Alsarra, I A et al, 2005). ZETA POTENTIAL ANALYSIS
The zeta potential was analyzed (Varaporn
ENTRAPMENT EFFICIENCY Buraphacheep Junyaprasert et al, 2008) for proniosomal
powder by MALVERN ZETASIZER in BIRLA
To evaluate the loading capacity of proniosomal INSTITUTE OF TECHNOLOGY, MESRA, (RANCHI).
gels of ibuprofen, 20mg of the proniosomal gel was weighed
and dispersed in distilled water and warmed a little for the STABILITY STUDIES FOR PRONIOSOMAL GEL
formation of niosomes. The niosome dispersion so obtained
was centrifuged at 18,000 rpm for 40 min at (Remi Stability study was carried out to investigate the
centrifuge).The clear fraction was used for the determination degradation of drug from proniosomal gel during storage.
of free drug at 257 nm UV spectrophotometrically (Ankur The proniosomal gel formulations composed of span-60 and
Gupta et al, 2007). cholesterol sealed in glass vials and stored in 4°C, 25°C and
40°C temperatures for a period of 2 months Samples from
%EE = [(Ct-Cf)/Ct] X 100 each batch were withdrawn after the definite time intervals
Where, and converted into noisome and the residual amount of drug
Ct is the concentration of total drug. in the vesicles were determined (Ankur Gupta et al, 2007,
WHO 2006).
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Sudhamani T. et al. / International Journal of Biopharmaceutics. 2010; 1(2): 75-81.

RESULTS AND DISCUSSION this revealed that the drug release follows a non fickian
Proniosomes of ibuprofen were prepared by slurry diffusion.
method. In this method drug, non ionic surfactant and Vesicles with smaller diameter are believed to better
cholesterol were mixed in organic solvent and added to permeate through the skin as smaller vesicles tend to fuse
maltodextrin carrier. The use of maltodextrin as the carrier in readily. Shape and surface characteristic of proniosome were
the proniosome preparation permitted flexibility in the examined by Scanning Electronic Microscopy analysis.
amounts of surfactants and other components, which greatly Surface morphology showed the smooth surface of optimised
enhances the potential application of proniosomes in a proniosomal formulation Figure.1.
scaled-up production environment. The zeta potential value for the optimised
The drug content and entrapment efficiency were proniosomal powder F4 was found to be-28.3mV Figure 4. A
studied for all the nine formulations represented in table 2. value of ±25 mV (positive or negative) was taken as the
The entrapment efficiency was found to be highest with the arbitrary value that separates low-charged surfaces from
formulation F4 (96.57%), which may have an optimum highly-charged surfaces.
surfactant, maltodextrin ratio to provide a high entrapment of The proniosomal powder showed good stability for
ibuprofen. F4 formulations. Stability studies of the optimized
The release study was conducted for all the nine proniosomal gel were performed. The percentage of drug
formulations as shown in the Figure 2 and 3. Most of the retained in the span-60 vesicles after a period of 2 months for
formulations were found to have a linear release and the 4°C, 25°C, 40°C was found to be were 95.72%, 90.45% and
formulations were found to provide approximately 84.65% respectively Figure 5. From this it can be concluded
80%release within a period of 12 hours. The formulation that proniosomes are stable to store under refrigeration
which have optimum ratio F4 was found to sustain the drug temperature with least leakage.
release than other formulations. Among all formulations F4
was selected as best formulation because of its highest CONCLUSION
entrapment efficiency and consistent release profile of On conclusion, this novel drug delivery system i.e.
ibuprofen. proniosome as compared to liposome or niosome represent a
Cholesterol, which has a property to abolish the gel significant improvement by eliminating physical stability
to liquid transition of niosomes, this found to prevent the problems, such as aggregation or fusion of vesicles and
leakage of drug from the niosomal formulation. The slower leaking of entrapped drugs during long-term storage.
release of drug from multilamellar vesicles may be attributed Proniosomes derived niosomes are superior in their
to the fact that multilamellar vesicles consist of several convenience of storage, transport, and dosing as compare to
concentric sphere of bilayer separated by aqueous niosomes prepared by conventional method. By these facts
compartment. study can be concluded by Ibuprofen was successfully
The zero order plots showed the zero order release entrapped within the lipid bilayer of the vesicles with high
characteristics of the formulation, which was confirmed by efficiency and said that proniosomes based niosomal gel
the correlation value which was found to be nearer to one. formed from span 60, cholesterol using maltodextrin as a
Correlation value of Higuchi’s plot revealed that the carrier was a promising approach to sustain the drug release
mechanism of drug release was diffusion. The in vitro kinetic for an extended period of time and by that reducing the side
data subjected to log time vs log drug release transformation effects related to GI irritation.
plot (peppa’s model), the value lies were found to be n>0.45

Table.1 Compositions of Proniosome Batches of Ibuprofen.


Formulation Code Drug (mg) Span 60 (mg) Cholesterol (mg) Maltodextrin (mg)
F1 200 100 100 100
F2 200 200 100 200
F3 200 300 100 300
F4 200 400 100 400
F5 200 500 100 500
F6 200 100 100 500
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Sudhamani T. et al. / International Journal of Biopharmaceutics. 2010; 1(2): 75-81.

Formulation Code Drug (mg) Span 60 (mg) Cholesterol (mg) Maltodextrin (mg)
F7 200 200 100 500
F8 200 300 100 500
F9 200 400 100 500

Table.2 Drug content and Entrapment Efficiency.

S.No Formulation Code Average drug content (1ml) Entrapment Efficiency(%)

1 F1 17.20 ± 0.2 83.57 ± 1.01


2 F2 18.24 ± 0.23 84.94 ± 2.01
3 F3 18.45 ± 0.28 86.54 ± 1.91
4 F4 19.96 ± 0.32 96.57 ± 1.08
5 F5 19.42 ± 0.56 87.16 ± 1.39
6 F6 17.88 ± 0.45 87.85 ± 1.21
7 F7 19.57 ± 0.22 93.53 ± 1.48
8 F8 17.56 ± 0.42 93.26 ± 1.06
9 F9 17.62 ± 0.38 88.66 ± 1.62

Figure .1 SEM PHOTOGRAPHY OF PRONIOSOMAL POWDER FOR F4 FORMULATION


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Sudhamani T. et al. / International Journal of Biopharmaceutics. 2010; 1(2): 75-81.

Figure .2 COMPARATIVE IN VITRO RELEASE STUDIES FROM F1 – F5

COMPARATIVE STUDY FROM F1 - F5

90
80
Percentage Drug Release

70
F1
60
F2
50
F3
40
F4
30
F5
20
10
0
0 5 10 15
TIME IN HOURS

Figure .3 COMPARATIVE IN VITRO RELEASE STUDIES FROM F6 – F9

COMPARATIVE STUDY FROM F6 - F9

80

70

60

50

40
Percentage Drug

F6
30
F7
20
Release

10

0
0 2 4 6 8 10 12 14
TIME IN HOURS
Sudhamani T. et al. / International Journal of Biopharmaceutics. 2010; 1(2): 75-81. 80

Figure. 4 Zeta potential report of Proniosomal powder for F4 formulation


Sudhamani T. et al. / International Journal of Biopharmaceutics. 2010; 1(2): 75-81. 81

Figure .5 Stability study data for F4 Formulation

STABILITY STUDY FOR F4 FORMULATION


Percentage Drug Retained

105
100
95 4 degree
25 degree
90
40 degree
85
80
0 20 40 60 80
DAYS

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