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In vitro Dynamics of Ibuprofen Incorporated Proniosomal Gel

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Aim: The research was aimed to encapsulate the ibuprofen with proniosomal gel and facilitate ibuprofen release in sustained manner for sustained drug release. Methods:Different proniosomal gels of ibuprofen were formulated with Span 20/Span 80 and soya lecithin using the method described in literature. In all formulations cholesterol concentration was kept constant. The prepared proniosomal gels were evaluated for chemical incompatibility by FT-IR, vesicle size analysis, encapsulation efficiency, in vitrodrug permeation and in vitrodrug release kinetics were performed. Results: The principal absorption peaks of ibuprofen were retained in the proniosomal gels indicating that there was no interaction between ibuprofen and excipients. Vesicular diameter markedly depended on the type of the non-ionic surfactant used. As the outer diameter depends on the HLB value of surfactant, the vesicular diameter was less for proniosomes prepared using Span 80 (low HLB). The encapsulation efficiency was more for the proniosomal gels prepared using Span 20. Proniosomal gel prepared using Span 80 showed higher flux across the membrane due to its leaky membrane. The order of ibuprofen release from the proniosomal gel was PN2>PN4>PN1>PN3. Conclusion:The optimized proniosomal gel formulation PN3 containing Span 20 exhibited prolonged ibuprofen release profiles. Fickian diffusion mechanism was observed with the PN3 formulation which was due to the sustained release property. The results indicated that the proniosomal gel would be an effective transdermal delivery system for ibuprofen.
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PB Indian Journal of Pharmaceutical Education and Research | Vol 47 | Issue 4 | Oct–Dec, 2013
Indian Journal of Pharmaceutical Education and Research | Vol 47 | Issue 4 | Oct–Dec, 2013 59
www.ijper.org
Pharmaceucal Research
Pharmaceucal Research
In vitro Dynamics of Ibuprofen Incorporated
Proniosomal Gel
Thulasi Chowdary G, Harini Chowdary V*, Vandana KR, Jayasri V and Prasanna Raju Y
Department of Pharmaceutics, Sree Vidyankethan College of Pharmacy, A. Rangampet, Tirupati, 517102, India
Submission Date: 24-8-2013; Review completed: 22-10-2013; Accepted Date: 21-1-2014
ABSTRACT
Aim: The research was aimed to encapsulate the ibuprofen with proniosomal gel and facilitate ibuprofen release in
sustained manner for sustained drug release. Methods: Different proniosomal gels of ibuprofen were formulated
with Span 20/Span 80 and soya lecithin using the method described in literature. In all formulations cholesterol
concentration was kept constant. The prepared proniosomal gels were evaluated for chemical incompatibility by
FT-IR, vesicle size analysis, encapsulation efficiency, in vitro drug permeation and in vitro drug release kinetics
were performed. Results: The principal absorption peaks of ibuprofen were retained in the proniosomal gels
indicating that there was no interaction between ibuprofen and excipients. Vesicular diameter markedly depended
on the type of the non-ionic surfactant used. As the outer diameter depends on the HLB value of surfactant, the
vesicular diameter was less for proniosomes prepared using Span 80 (low HLB). The encapsulation efficiency
was more for the proniosomal gels prepared using Span 20. Proniosomal gel prepared using Span 80 showed
higher flux across the membrane due to its leaky membrane. The order of ibuprofen release from the proniosomal
gel was PN2>PN4>PN1>PN3. Conclusion: The optimized proniosomal gel formulation PN3 containing Span
20 exhibited prolonged ibuprofen release profiles. Fickian diffusion mechanism was observed with the PN3
formulation which was due to the sustained release property. The results indicated that the proniosomal gel
would be an effective transdermal delivery system for ibuprofen.
Keywords: encapsulation efficiency, permeation, flux, fickian diffusion, transdermal delivery.
INTRODUCTION
Drug delivery using colloidal particulate
carriers such as liposomes1 and niosomes2,3
have distinct advantages over conventional
drug delivery systems. The colloidal par-
ticulate systems act as drug reservoir and
can adjust the drug release rate by modi-
cation of the particle composition or
the surface characteristics. Niosomes are
microscopic non-ionic surfactant vesicles
with spherical, unilamellar, bilayered, mul-
tilamellar and polyhedral structures. Nio-
somes can be developed by the hydration
of non-ionic surfactants viz. alkyl or dial-
kyl polyglycerol class, ester linked sorbitan,
polysorbates with or without incorporation
of cholesterol.4 Niosomal delivery system is
a potential alternative to liposomal delivery
for many drug candidates, due to its highest
chemical stability offered over liposomes.
Additionally, variable purity of phospho-
lipids used in liposomes and their higher
cost could be effectively addressed by nio-
somes.5,6
Though niosomes are advantageous over
liposomes, aqueous niosomal dispersion
has posed some unanswered questions
such as instability associated with aggrega-
tion, fusion and hydrolysis of the encapsu-
lated drug. Thus, niosome has limited shelf
life. In order to circumvent stability associ-
ated problems, proniosomes were initiated.
‘Proniosomes’ are dry, free-owing granu-
lar product which can form multilamellar
dispersion upon hydration.7 The pronio-
somes offer ease of storage, transportation
DOI: 10.5530/ijper.47.4.8
Address for
correspondence
Ms. Harini Chowdary
Vadlamudi
Asst. Professor, Department
of Pharmaceutics, Sree
Vidyanikethan College
of Pharmacy, Tirupati -
517102, India.
Mobile: +91-9494598424
Email:
vadlamudi.harini@gmail.com
Thulasi Chowdary G, et al.: Ibuprofen proniosomal gel
60 Indian Journal of Pharmaceutical Education and Research | Vol 47 | Issue 4 | Oct–Dec, 2013
Indian Journal of Pharmaceutical Education and Research | Vol 47 | Issue 4 | Oct–Dec, 2013 61
and extended shelf-life over niosomal dispersions.
Proniosomes can deliver the active drug moieties very
effectively through the transdermal route.5,8
Ibuprofen [2-(4-isobutylphenyl) propionic acid] is
a non-steroidal anti-inammatory drug (NSAID)
that inhibits both the isoforms of cyclo-oxygenase
enzyme. It is used in the treatment of inammation,
osteoarthritis, rheumatoid arthritis, primary dysmen-
orrhea, mild to moderate pain and fever.9 Being class
II, ibuprofen has elimination half-life of 2 h and
cause ulceration, bleeding and perforation in the GI
tract which limits its oral use. Sustained release dos-
age form of ibuprofen that may have a potential to
keep therapeutic level in plasma for prolonged period
may evade its toxic effects on GIT and will improve
its area of application.10 Transdermal delivery of ibu-
profen is the best way to avoid the post-oral admin-
istration problems of GIT. Moreover, it can reduce
the frequency of administration and improve patient
compliance.11
Therefore, the present study was aimed to develop ibu-
profen proniosomal delivery systems using non-ionic
surfactants Span 20 and Span 80, cholesterol and soya
lecithin. The prepared systems hypothesized to have
sustained release for ibuprofen over a period of time.
The proniosomes prepared were evaluated for the drug
content, entrapment efciency, homogeneity and in vitro
drug release. The effect of surfactants and the soya leci-
thin on the drug encapsulating capacity as well as on the
sustained action was also evaluated.
MATERIALS AND METHODS
Ibuprofen was obtained as a gratis from M/s. A-Z
Pharmaceuticals, Chennai. Span 20 and Span 80 were
obtained from M/s. Loba Chem Ltd., Mumbai. Cho-
lesterol was procured from M/s. HiMedia Lab Pvt
Ltd., Mumbai. Soya lecithin (phospholipoin 80H)
was obtained as a gift sample from Lipoids (Ludwig-
shafen), Germany. All other chemicals used were of
analytical grade and were used without any chemical
modications.
Preparation of proniosomal gel
Accurately weighed quantities of ibuprofen, non-ionic
surfactants, soya lecithin and cholesterol were taken
in a clean and dry wide mouthed glass vial and
2.5 ml of ethanol was added. The open end of the
vial was covered with a lid to avert loss of solvent and
heated to 65±3°C until the surfactant mixture dissolved
completely. Then 1.6 ml of phosphate buffer pH 7.4
(aqueous phase) was added to above mixture and heated
to get homogeneous dispersion. Then it was allowed to
cool until the dispersion is converted to proniosomal
gel.12 The composition of various proniosomal gels
were listed in Table 1.
Fourier transform infrared spectroscopy
Fourier Transform Infrared (FTIR) spectra of ibupro-
fen, PN1 and PN2 were recorded in a Thermo-IR 200
FTIR spectrophotometer. Potassium bromide pellet
method was employed and background spectrum was
collected under identical conditions. Each spectrum
was derived from 16 single average scans collected in
the range of 400–4000 cm−1 at the spectral resolution
of 2 cm−1.
Physical appearance
All the gel formulations were tested for their homoge-
neity by visual inspection. They were tested for their
appearance and presence of any gritty aggregates.
Vesicle size analysis
The proniosomal gels were diluted with phosphate
buffer pH 7.4 and were observed under polarized bin-
ocular microscope to determine the vesicle size. The
size distribution range and mean diameter were also
calculated.
Polarized photography
The prepared proniosomal gels were diluted using
phosphate buffer pH 7.4 and spread in a cavity slide and
covered with a cover slip. The slide was observed under
microscope with and without polarized light (Olympus,
BX 51-P). Photomicrographs were taken at suitable
magnications.
Encapsulation efciency
The proniosomal gel in the glass tube was diluted with
10 ml phosphate buffer pH 7.4. The aqueous suspen-
sion was sonicated for 20 min. The ibuprofen contain-
ing niosomes were separated from the un-entrapped
Table 1: Composition of Proniosomal Gels in mg
Formulation code Ibuprofen Cholesterol Soyalecithin Span 20 Span 80
PN1 1000 200 1800 1800 –
PN2 1000 200 1800 – 1800
PN3 1000 200 900 1800 –
PN4 1000 200 900 – 1800
Thulasi Chowdary G, et al.: Ibuprofen proniosomal gel
60 Indian Journal of Pharmaceutical Education and Research | Vol 47 | Issue 4 | Oct–Dec, 2013
Indian Journal of Pharmaceutical Education and Research | Vol 47 | Issue 4 | Oct–Dec, 2013 61
ibuprofen by centrifuging at 10,000 rpm for 30 min. The
supernatant liquid was collected and assayed at 225 nm.
The percentage of drug encapsulation (EE (%)) was
calculated by the following equation:6
EE% =CC
C
tf
t
-×100
where, Ct is the concentration of total ibuprofen and Cf
is the concentration of free ibuprofen.
Drug content
Ibuprofen content in the prepared proniosomal gels
was determined by dissolving a known quantity of the
gels in methanol. The contents were passed through
0.4 µm membrane lter. The ltrate was assayed upon
dilution with phosphate buffer pH 7.4.
In vitro permeation studies
The permeation of ibuprofen from proniosomal
formulations was determined by using vertical Franz
diffusion cell. Receptor compartment containing
phosphate buffer pH 7.4 was constantly stirred at
50 rpm using magnetic stirrer and the temperature
was maintained at 37±2° C. The aliquots were with-
drawn at 1, 2, 3, 4, 5, 6, 7 and 8 h. Soon after with-
drawal of the aliquots, the receptor compartment was
replaced with fresh buffer solution to maintain sink
conditions. The samples were analyzed for ibupro-
fen content using a UV-visible spectrophotometer at
225nm. The ux (J) was determined as the angular
coefcient of the curve obtained by plotting the
cumulative amount of the penetrated drug versus
time. The permeability coefcient (kp) of ibuprofen
was calculated using the following equation:13
k
J
C
p=
where, C is the initial concentration of drug in the for-
mulation applied to the membrane.
Transmission electron microscopy (TEM)
Morphology and structure of the optimized pro-
niosomal gel was stud ied using transmission elec-
tron microscopy (TEM) TOPCON 002B operating at
200 kV and capable of point-to-point resolution.
RESULTS AND DISCUSSION
FTIR
The FTIR spectra (Fig. 1) of the ibuprofen, PN1 and
PN2 showed major absorption peaks of ibuprofen at
2961.01 cm–1, 2900.79 cm–1, 2728.06 cm–1, 1717.17 cm–1,
1501.68 cm–1, 1458.12 cm–1, 1317.22 cm–1, 1248.81 cm–1,
1227.50 cm–1, 935.12 cm–1, 863.34 cm–1, 777.39 cm–1,
586.57 cm–1 indicating the presence of CH3 asymmetric
stretching, hydroxyl stretching, CH2 symmetric stretch-
ing, C=O Stretching vibration of –COOH group,
Aromatic C-C stretching, CH-CO deformation, O-H
in plane deformation, C-H in plane deformation, C-C
stretching, CH3 rocking vibration, C-H out of plane
vibration, CH2 rocking vibration and C-C deformation
respectively. Appearance of extra peaks at 3059.19 cm–1
in both the formulations and appearance of peaks near
2153 cm–1 and 2357 cm–1 for PN2 may be due to any of
Span, cholesterol and lecithin.
Physical appearance
All the formulations were homogenous with glossy
appearance.
Vesicle size analysis
Vesicle diameter was determined by diluting the pro-
niosomal gel with phosphate buffer pH 7.4. The effect
of various concentrations of surfactants (Span 20 and
Span 80) on the vesicle size of proniosomes was deter-
mined by keeping the cholesterol concentration as
constant. The vesicular diameter values of ibuprofen
loaded proniosomal gels are shown in Table 2. It was
observed that the vesicular diameter of proniosomes
prepared with Span 80 was less compared to that of
Span 20. The outer dimensions and size of ibuprofen
proniosomes are depended on HLB values of Span
Figure 1: FTIR spectra of proniosomal gels.
Thulasi Chowdary G, et al.: Ibuprofen proniosomal gel
62 Indian Journal of Pharmaceutical Education and Research | Vol 47 | Issue 4 | Oct–Dec, 2013
Indian Journal of Pharmaceutical Education and Research | Vol 47 | Issue 4 | Oct–Dec, 2013 63
20/80. The lower the HLB value of surfactant, the
smaller initial size of the niosomal vesicles which is a
result of decreased surface free energy with increase in
hydrophobicity as it was observed from Span 80 with
HLB 4.3 showed less vesicular diameter for PN2 and
PN4 compared to proniosomes (PN1 and PN3) pre-
pared with Span 20 with HLB 8.6. Reduction in vesicu-
lar diameter was observed with increase in soya lecithin
concentration which is believed to be due to increased
hydrophobicity. The order of average vesicular diam-
eter is PN3>PN1>PN4>PN2. The results imply that
type of non-ionic surfactant and the concentration of
the soya lecithin have a profound inuence on vesicular
diameter of proniosomes.
Encapsulation efciency
The niosomes formed from Span 20 containing pronio-
somal gel has showed better entrapment compared to
that of Span 80 as shown in Table 2. This is due to that
the entrapment efciency depends on the structure of
the surfactant. Longer the saturated alkyl chain of the
surfactant, greater is the entrapment efciency. Span 80
possess unsaturated alkyl chain which made the chains
bend and more permeable when it forms membrane
which ultimately leads to lowest entrapment efciency.14
It suggests that the alkyl chain of surfactant is a cru-
cial factor in entrapment efciency and saturated chain
produces higher entrapment compared to unsaturated
chain. Effect of soya lecithin on entrapment efciency
was not signicant.
Microscopic images
Microscopic images were taken to nd the vesicle
morphology. From the images (Fig. 2) it was evident
that the vesicles in the proniosomal gel were discrete
and almost spherical in shape. PN1 and PN2 show dis-
crete spherical particles with various sizes, PN3 shows
discrete particles of various size, PN4 shows discrete
particles out of which majority of vesicles are spheri-
cal and some of them possess fractured/roughen
edges. The colour variation of the photographs is due
to the concentration variation of soya lecithin in the
formulations. The difference in the size of the vesicles
is purely due to the variation in the magnication.
Drug content
Drug content determines the amount of ibuprofen
in the prepared proniosomal gels. Results showed the
more uniformity of the drug in the proniosomal gels
and indicated the less drug loss in formulations as
shown in Table 2. The drug content was highest in PN1
formulation which could be due to non-ionic surfactant
Span 20.
In vitro permeation of ibuprofen from the
proniosomal gel
The permeation of drug from proniosomal gels con-
taining Span 80 is high compared to that of Span 20.
This was due to unsaturated alkyl chain structure in
Span 80 that led to leakier niosomal membrane. Hence,
fast drug release was observed in case of ibuprofen pro-
niosomal gels prepared using Span 80. In addition, leci-
thin acted as penetration enhancer. Hence increase in
concentration of lecithin led to enhanced drug release
with the same concentration of span 20/span 80 as
it was observed from the ux and permeability coef-
cient (Table 2, Fig. 3). Sustained drug release pattern
was observed with ibuprofen proniosomal gel prepared
using Span 20. The percent drug release at the end of
8 h was found to be 86.3, 94.1, 82.4 and 90.3% for PN1,
PN2, PN3 and PN4 respectively (Fig. 4).
Transmission electron microscopy
The optimized proniosomal gel (PN3) was examined
micro scopically using Transmission Electron Micros-
copy (TEM). TEM showed that the particles had spher-
ical, uniform shapes. A dense, well-distributed pattern
was observed in PN3 (Fig. 5).
Release kinetics
The best t model for PN1 and PN3 was found to be
Higuchi release model with correlation coefcient ‘r’
Table 2: Drug Content, Flux and Permeability Coefcient of the Proniosomal Gel
Formulation code Vesicle size (µm) % Drug content Flux (μg cm2 h1)
Permeability
coefcient (kp)
(cm h1)
% Entrapment
efciency
PN1 12.69±0.14 85±0.71 98.02±0.23 4.90×10476.7±0.96
PN2 6.66±0.63 64±0.65 170.88±0.67 8.54×10463.5±0.88
PN3 13.65±0.24 81.2±0.94 88.42±0.41 4.42×10475.2±0.28
PN4 9.98±0.57 61.2±0.89 146.49±0.97 7.32×10460.6±0.79
Values are expressed in mean±S.D. (n = 3)
Thulasi Chowdary G, et al.: Ibuprofen proniosomal gel
62 Indian Journal of Pharmaceutical Education and Research | Vol 47 | Issue 4 | Oct–Dec, 2013
Indian Journal of Pharmaceutical Education and Research | Vol 47 | Issue 4 | Oct–Dec, 2013 63
values 1.00 and 0.999 describing the Fickian diffusion
pattern as shown in Table 3. Whereas PN2 and PN4
exhibited both Hixson-Crowell with r values 0.9978 and
0.9872 respectively indicating the release rate is limited
by drug particles dissolution rate rather than by diffu-
sion. The ‘n’ value ranging between 0.8–0.99 indicates
non-ckian diffusion and suggests that more than one
type of release phenomenon is involved.
CONCLUSION
The in vitro permeation of ibuprofen from the pronio-
somal gels of various compositions was studied. Ibupro-
fen was effectively incorporated into proniosomal gels.
The higher encapsulation efciency was found in a formu-
lation containing span 20. Soya lecithin has no profound
effect on entrapment efciency. Ibuprofen proniosomal
gels containing span 20 have exhibited prolonged drug
Figure 4: n vitro drug Release of ibuprofen from proniosomal gels.
Values are presented as mean±S.D. (n = 3).
Figure 3: Cumulative amount of drug versus time plot. Values are
presented as mean±S.D. (n = 3). Figure 5: TEM photograph (69,750 × magnifica tion) of pronioso-
mal gel (PN-3).
Figure 2: Microscopic images of ibuprofen proniosomes.
Table 3: Release Kinetics of Proniosomal Gels
Model PN1 PN2 PN3 PN4
Zero order r 0.9841 0.9576 0.9853 0.9575
First order r 0.9841 0.9576 0.9709 0.9575
Higuchi r 1.0000 0.9887 0.999 0.9842
Peppas r 0.9906 0.9885 0.9902 0.9849
Hixson-Crowell r 0.9981 0.9936 0.9978 0.9872
Baker-Lonsdale r 0.9749 0.986 0.9158 0.9818
Weibull r 0.9675 0.9575 0.9696 0.9673
Thulasi Chowdary G, et al.: Ibuprofen proniosomal gel
64 Indian Journal of Pharmaceutical Education and Research | Vol 47 | Issue 4 | Oct–Dec, 2013
Indian Journal of Pharmaceutical Education and Research | Vol 47 | Issue 4 | Oct–Dec, 2013 PB
release proles. Thus, it is concluded that the proniosomal
gel approach is said to be a promising drug delivery system
for BCS class II drugs such as ibuprofen and especially
this method is easy to prepare, economic and reproduc-
ible. Further studies are required to explore the suitability
of proniosomal gel drug delivery approach for various
therapeutic drug candidates with commercial viability.
ACKNOWLEDGEMENT
The authors are thankful to the management of Sree
Vidyanikethan College of Pharmacy, A. Rangampet,
Tirupati, Andhra Pradesh, India for providing the nec-
essary facilities to carry out the research work.
CONFLICTS OF INTEREST
The authors report that this article content does not
have any conicts of interest.
REFERENCES
1. Betageri G, Habib M. Liposomes as drug carriers. Pharm Eng 1994;14:
76–77.
2. Schreier H, Bouwstra J. Liposomes and niosomes as topical drug
carri ers: dermal an d transderma l drug deliver y. J Cont Rel 1994; 30:
1–15.
3. Hu C, Rhodes DG. Proniosomes: A Novel Drug Carrier Preparation. Int J
Pharm 2000; 206:110–122.
4. Malhotra M, Jain NK. Niosomes as Drug Carriers. Indian Drugs 1994; 31:81–86.
5. Vora B, Khopade AJ, Jain NK. Proniosome based transdermal delivery of
levonorgestrel for effective contraception. J Cont Rel 1998; 54:149–165.
6. Jia-You F, Song-Yih Y, Pao-Chu W, Yaw-Bin H, Yi-Hung T. In vitro skin
permeation of estradiol from various proniosome formulations. Int J Pharm
2001; 215:91–99.
7. Ibrahim A A, Bosela AA, Ahm ed SM, Mahrous G M. Pronioso mes as a
drug car rier for tra nsdermal deli very of ketorol ac. Eur J Pharm Bio pharm
2005; 59:485– 490.
8. Huang BY, Jung BH, Chung SJ, Lee MH, Shim CK. In vitro skin permeation
of nicotine from proliposomes. J Cont Rel 1997; 49:177–184.
9. Insel P. Analgesic-antipyretic andantiinammatory agents.In: Hardman
JC, edito r. Goodman & Gilman’s Th e Pharmacolo gical Basis of
Therapeutics, 9th e d. New York: McGraw -Hill publishers; 1996. p. 6 39.
10. Akas h MS, Iqbal F, Raza M, Rehman K, Ahmed S, Sh ahzad Y
and Hussain Shah SN Characterization of Ethylcellulose and
Hydroxypropyl Methylcellulose Microspheres for Controlled Release
of Flurbi profen J Pharm Dr ug Del Res. 2013, 2:1 1–10.
11. M ahmoud M, Omai ma AS, Mohamme d AH, Nagia AM . Effect of some
formulation parameters on urbiprofen encapsulation and release
rates of niosomes prepared from proniosomes. Int J Pharm 2008; 361:
10 4 –111 .
12. G upta A, Sunil K P, Bal amurugan M, Ma mta S, Daksh B. Des ign and
developm ent of a pronioso mal transder mal drug delive ry system for
captopr il. Tropical J Phar m Res 2007; 6:687–6 93.
13. Marta PA, Ana LS, Marcos S. Pharmaceutical Nanotechnology: Human
skin pene tration and distribution of n imesulide fr om hydrophilic gels
contai ning nanocar riers. Int J Pha rm 2007; 341:215–220.
14. WanLSC,LeePFS. Inuenceofnon-ionicsurfactantsoninterfacialtension
in o/w system. Can J Pharm Sci 1974; 8:136–139.
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The concept of carriers to deliver drugs to target organs and modify drug disposition has been widely discussed. The majority of such reports have concerned the use of phospholipid vesicles or liposomes, which exhibit certain disadvantages, such as chemical instability, high cost and variable purity of lipids used, which militates against their adoption as drug delivery vehicle. Alternatives to phospholipids are thus of interest from the technical viewpoint and could also allow a wider study of the influence of chemical composition on the biological fate of vesicles.
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The objective of this study was to design and optimize polymeric microspheres of flurbiprofen (FLB) with ethylcellulose (EC) and hydroxypropyl methylcellulose (HPMC) using response surface methodology. EC and HPMC were taken as independent variables whereas; the dependent variables were % drug release at pH 1.2, 4.5 and 7.4. FTIR spectra and TGA showed no significant difference between drug and polymers. DSC and XRD studies exhibited molecular dispersion of FLB within microspheres. Contour plots were drawn to predict the relationship between dependent and independent variables. Both polymers revealed their significant effects on drug release that followed the zero order which was further verified by the lowest values of Akaike information criterion. The mechanism of drug release followed super case II type of drug release. This study helped unraveling the influence of two factors on in-vitro drug release and thereby, proposed an appropriate sustained drug release formulation. variables but among them, the response surface methodology (RSM) is one that has currently been used to develop a versatile relationship between investigational response and a set of contributing variables [1]. RSM is the set of mathematical and statistical technique that is used to analyze the problems that are influenced by several variables during manufacturing process. It is used only when few significant factors are involved in the optimization of process variables. It also reduces the number of experimentations and saves time, thus corroborating to be more effectual and cost-effective than traditional methods for the preparation of dosage forms [2]. Flurbiprofen (FLB) is non-steroidal anti-inflammatory (NSAID) drug that is effective for the treatment of fever, pain and inflammation in the body. The major untoward reactions that appear after FLB administration include gastrointestinal tract (GIT) including peptic ulcer, dyspepsia, cramping, gastric bleeding resulting in the treatment failure and patient incompliance [3]. FLB requires frequent administration round the clock to achieve its desired therapeutic effects due to its short biological half-life (2-6 hrs). Therefore, sustained release dosage form of FLB that may have a potential to keep therapeutic level of FLB in plasma for prolonged period may evade its toxic effects on GIT and will improve its area of application. Oral Sustained release dosage forms are known to have many advantages over their immediate counterparts nevertheless; the drug must be dispersed adequately through well defined polymeric matrix system [4]. Biodegradable and non-biodegradable polymers have extensively been used for the release retarding efficacy [5,6]. Hydrophilic and lipophilic polymers are being widely used to control the release behavior of drug from matrix [7]. The ability of polymeric microspheres to encapsulate variety of drugs, high bioavailability and sustained release characteristics make them ideal vehicle for many control release applications [8]. Ethyl cellulose (EC) is a lipophilic polymer and has been widely used and broadly studied for both lipophilic hydrophilic drugs in the preparation of CR dosage system [9]. EC microspheres showed good extended drug release properties, especially for highly lipophilic drugs as this polymer has excellent membrane-forming ability, durability and low cost, however its flexibility is relatively inferior [10]. Extensive research is being carried out utilizing EC as a drug carrier to achieve the desirable drug release profile. Large doses of FLB can be incorporated in microspheres with EC because of its least chances of dose dumping which may result in severe gastric and mucosal irritation. Hydroxypropyl methylcellulose (HPMC) is another semi-synthetic ether derivative of cellulose used in this study. Due to its non-toxic nature, ease of compression and accommodation to high levels of drug loading, it has been a dominant hydrophilic vehicle used in controlled release dosage forms [11]. The hydration rate of HPMC increases with the increase of hydroxypropyl content and solubility which is pH independent. The objective of this research work was to optimize the formulation of flurbiprofen loaded EC/HPMC microspheres by solvent evaporation method using RSM which showed a controlled release of flurbiprofen from these microspheres. Further we focused on the influence of each variable along with another variable on drug loading, entrapment efficiency, percent recovery of microspheres,
Article
The skin permeation of estradiol from various proniosome gel formulations across excised rat skin was investigated in vitro. The encapsulation efficiency and size of niosomal vesicles formed from proniosomes upon hydration were also characterized. The encapsulation (%) of proniosomes with Span surfactants showed a very high value of ≒100%. Proniosomes with Span 40 and Span 60 increased the permeation of estradiol across skin. Both penetration enhancer effect of non-ionic surfactant and vesicle-skin interaction may contribute to the mechanisms for proniosomes to enhance estradiol permeation. Niosome suspension (diluted proniosomal formulations) and proniosome gel showed different behavior in modulating transdermal delivery of estradiol across skin. Presence or absence of cholesterol in the lipid bilayers of vesicles did not reveal difference in encapsulation and permeation of the associated estradiol. The types and contents of non-ionic surfactant in proniosomes are important factors affecting the efficiency of transdermal estradiol delivery.
Article
A critical analysis of (trans) dermal delivery of substances encapsulated within liposomes and niosomes is presented. Topical liposomes or niosomes may serve as solubilization matrix, as a local depot for sustained release of dermally active compounds, as penetration enhancers, or as rate-limiting membrane barrier for the modulation of systemic absorption of drugs. The mechanism(s) of vesicle-skin interaction and drug delivery are being extensively investigated using radioactive- or fluorescence-labeled marker molecules and drugs, and various electron and (laser) light microscopic visualization techniques, and different models describing the interaction with and fate of vesicles in the skin have been proposed. With the current experimental data base on hand, most investigators agree that direct contact between vesicles and skin is essential for efficient delivery, although phospholipids per se apparently do not penetrate into deeper skin layers. Investigators have mostly focused on dermal corticosteroid liposome products. However, localized effects of liposome-associated proteins such as superoxide dismutase, tissue growth factors and interferons appear also to be enhanced. The delivery of liposome-encapsulated proteins and enzymes into deeper skin layers has been reported, although the mechanism of delivery remains to be elucidated. An objective assessment of the performance of topical liposome formulations vs. conventional dosage forms is frequently obscured by investigators comparing equal concentrations, rather than equivalent thermodynamic activities of their respective formulations. We conclude that liposomes and niosomes may become a useful dosage form for a variety of dermally active compounds, specifically due to their ability to modulate drug transfer and serve as nontoxic penetration enhancers.
Article
The feasibility of proliposomes as a sustained transdermal dosage form was examined. Proliposomes containing varying amount of nicotine were prepared by a standard method using sorbitol and lecithin. The porous structure of sorbitol in the proliposomes was maintained, indicating that the majority of lecithin and nicotine is deposited within their porous matrix of the sorbitol particles. As a consequence, the flow properties of the proliposome particles was comparable to that of original sorbitol particles. Microscopic observation revealed that proliposomes are converted to liposomes almost completely within minutes following contact with water. It indicates that proliposomes may form liposomes by the sweat when they are applied on the skin under occlusive conditions in vivo. The size distribution of the reconstituted liposomes and nicotine release to pH 7.4 phosphate buffer from them were not significantly affected by the content of nicotine. The release pattern was apparently identical to the Exodus® patch, a commercially available transdermal nicotine formulation. We also studied in vitro permeation of nicotine across rat skin from proliposomes in a modified Keshary–Chien diffusion cell where the experimental set up simulates in vivo application of the proliposomes under an occlusive condition. The nicotine flux from proliposomes was initially retarded compared with that of nicotine powder. The flux from proliposomes appeared to remain constant throughout the experimental period compared with that of nicotine powder, indicating that nicotine may be delivered across the skin in a sustained manner at a constant rate from proliposomes. These results, therefore, indicate that sustained transdermal delivery of nicotine is feasible using proliposomal formulations if the formulations are topically applied under occlusive conditions.
Article
A proniosome based transdermal drug delivery system of levonorgestrel (LN) was developed and extensively characterized both in vitro and in vivo. The proniosomal structure was liquid crystalline-compact niosomes hybrid which could be converted into niosomes upon hydration. The system was evaluated in vitro for drug loading, rate of hydration (spontaneity), vesicle size, polydispersity, entrapment efficiency and drug diffusion across rat skin. The effect of composition of formulation, amount of drug, type of Spans, alcohols and sonication time on transdermal permeation profile was observed. The stability studies were performed at 4 degrees C and at room temperature. The biological assay for progestational activity included endometrial assay and inhibition with the formation of corpora lutea. The study demonstrated the utility of proniosomal transdermal patch bearing levonorgestrel for effective contraception.
Article
A procedure is described for producing a dry product which may be hydrated immediately before use to yield aqueous niosome dispersions similar to those produced by more cumbersome conventional methods. These 'proniosomes' minimize problems of niosome physical stability such as aggregation, fusion and leaking, and provide additional convenience in transportation, distribution, storage, and dosing. This report describes the preparation of dispersions of proniosome-derived niosomes, comparison of these niosomes to conventional niosomes, and optimization of proniosome formulations. In addition, conventional and proniosome-derived niosomes are compared in terms of their morphology, particle size, particle size distribution, and drug release performance in synthetic gastric or intestinal fluid. In all comparisons, proniosome-derived niosomes are as good or better than conventional niosomes.