hydrogel drug delivery system
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P R E PA R AT I O N A N D C H A R AC T E R I S AT I O N O F
H Y D RO G E L B A S E D D RU G D E L I V E RY S YS T E M FO R
R E L E A S I N G F LU VA S TAT I N D RU G
Under the guidance ofDr. Smita Mohanty
Mohamed Adam.K(Reg.No.1007108017)
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Background of the work
• Fluvastatin – A Drug• Hydrogels : An Introduction
Method of Drug Loading
Preparation of PSA Hydrogel
Results and Discussion
Conclusion
References
Fluvastatin is a competitive inhibitor of HMG-CoA reductase, which is responsible for the conversion
of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate, a precursor of sterol, including cholesterol.
The ultimate result of this mechanism is a reduction of the plasma total cholesterol which is responsible for coronary
artery disease (CAD)
Administration of statins by oral rout is associated with several problems including diarrhea, constipation, indigestion
and does not usually provide rate-controlled release or target specificity.
Fluvastatin : Works against Hypercholesterolemia
Structural formula for fluvastatin
Shorter biological half life (2.5 hrs ) and Poor bioavailability (20%) has necessitated the administration of
repeated (20 to 40 mg twice a day ) and higher doses to obtain the desired therapeutic efficacy which often leads
to risk of toxicity.
B a c k g r o u n d o f t h e Wo r k
Hydrogel : Swellable Polymeric Materials
Hydrogels are three dimensional networks of hydrophilic polymers.
Hydrogels are water swollen polymer matrices, with a huge tendency to absorb water. Their ability to swell, under
physiological conditions, makes them an ideal material for biomedical applications .
Hydrogels can protect drugs from hostile environments, e.g. the presence of enzymes and low pH in the stomach.
Their porosity permits loading of drugs into the gel matrix and subsequent drug release at a pre-designed rate.
A c r y l i c b a s e d h y d r o g e l s h a v i n g h i g h c h a r g e t o m a s s r a ti o t h a n a n y o t h e r
p o l y m e r s
Impregnation of Hydrogel with drugs
Preparation of Drug Loaded Hydrogel
Preparation
40mg of MBA were dissolved in 10ml of stock solution (Neutralized Acrylic acid). About 4mg of APS and 0.5 ml of TEMED were added to prepare PSA Hydrogel.
Materials
Acrylic acid N,N-methylenebisacrylamide (MBA) - Cross linkerAmmoniumpersulfate (APS) - An Initiator N,N,N,N’-tetramethylethylenediamine
(TEMED) - An Accelerator Sodium hydroxide (NaOH) - Neutralizer
P r e p a r a ti o n o f P S A H y d r o g e l
Spectral Characterization of PSA Hydrogel
FTIR Spectra of stock solution
83
5.7
96
2.1
99
2.6
10
60
.5
12
76
.0
13
50
.9
14
25
.9
15
36
.0
16
36
.7
33
16
.1
Stock soln
10
20
30
40
50
60
70
80
90
100
110
%T
500 1000 1500 2000 2500 3000 3500 4000
Wavenumbers (cm-1)
1640 cm-1, related to the C=C acrylate stretch mode ;1420 cm-1, related to C–C.
FTIR Spectra of crosslinked PSA gel
13
13
.5
13
55
.6
14
02
.5
14
54
.0
15
40
.7
16
46
.1
16
57
.8
32
43
.5
0.4 % gel
-20
-10
0
10
20
30
40
50
60
70
80
90
100
110
%T
500 1000 1500 2000 2500 3000 3500 4000
Wavenumbers (cm-1)
When sodium acrylate is polymerized the C=C bond is converted to C–C bond. This was clearly captured in the FTIR spectra as
the size of the absorption peak at 1645 cm-1 reduced with progress of polymerization.
R e s u l t s a n d D i s c u s s i o n
Effect of Crosslinker Concentration
0 50 100 150 200 250 300 350 4000
500
1000
1500
2000
2500
0.2% CL
0.4% CL
0.8% CL
1% CL
Time (min)
Sw
elli
ng
rat
io (
%)
Swelling behavior of Poly(sodium acrylate) hydrogels with different crosslinker concentration in distilled water at
room temperature.
0.00 500.00 1000.00 1500.00 2000.000.00
200.00
400.00
600.00
800.00
1000.00
1200.00
1400.00
1600.00
1800.00
pH=2pH=3pH=4pH=5pH=6pH=7
Sw
elli
ng
Ra
tio
%
Swelling behavior of Poly(sodium acrylate) hydrogels at different pH
Time (min)
Effect of pH on Swelling Ratio
FTIR Spectra of drug loaded PSA gelFTIR Spectra of crosslinked PSA gel
Conformation of Fluvastatin Loading
The dependency of the drug loading amount on the incubation time
Effect of Incubation Time on Drug Loading
The dependency of the drug loading amount to the crosslinker concentration
Effect of Amount of Crosslinker on Drug Loading
Release of fluvastatin from hydrogel carrier as a function of time
Drug Release as a Function of Time
Poly(sodium acry late) hydrogels was synthes ized
through cross l ink ing of acry l i c ac id/acry lamide.
Swel l ing capac i ty of the hydrogels i s aff ected by
the cross l inker (MBA) concentrati on, so that the
swel l ing i s decreased by increas ing the MBA
concentrati on. The superabsorbent hydrogels
exhib i ted h igh sens iti v i ty to pH , so that , severa l
swel l ing changes of the hydrogel were obser ved
in pH var iati ons of a wide range (2-7) and
eff ecti ve enough for drug de l ivery .
C o n c l u s i o n
[1]. V. Bekiar, P. Lianos; Poly (Sodium Acrylate) Hydrogels as Potential pH-Sensitive Sorbents for the Removal of Model Organic and Inorganic Pollutants from Water Global NEST Journal, Vol 12, No 3, pp 262-269, 2010 [2]. A. Pourjavadi, H. Hosseinzadeh; Synthesis, Characterization and Swelling Behavior of Gelatin-g-poly(sodium acrylate)/Kaolin Superabsorbent Hydrogel Composites; Journal of Composite Materials 2007 41: 2057 [3]. Bahia A. Moussa, Ashraf H. Abadi, Hanan E. Abou-Youssef and Marianne A. Mahrouse; Spectroscopic and chromatographic determination of fluvastatin sodium in presence of its acid degradate; International Journal of PharmTech Research; CODEN (USA): IJPRIF ISSN : 0974-4304 Vol.2, No.1, pp 875-898, Jan-Mar 2010 & Pattern Application Publications: US 2008/0200532 A1 [4]. Murat Sen, Arzu Yakar; Controlled release of antifungal drug terbinafine hydrochloride from poly(N-vinyl 2-pyrrolidone/itaconic acid) hydrogels; International Journal of Pharmaceutics 228 (2001) 33–41
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[8]. M. Morishita, T. Goto, K. Nakamura, A. M. Lowman, K. Takayama, and N. A. Peppas. Novel oral insulin delivery systems based on complexation polymer hydrogels: Single and multiple administration studies in type 1 and 2 diabetic rats. J. Control. Release. 110:587–594 (2006). doi:10.1016/j.jconrel. 2005.10.029.
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[11]. Hwang S-J, Park H, Park K. Gastric retentive drug delivery systems. Crit Rev Ther Drug Carrier Syst 1998; 15:243–284.
[12]. Qiu Y, Park K. Environment-sensitive hydrogels for drug delivery. Adv Drug Delivery Rev 2001; 53:321–339.
[13]. Siegel RA, Falamarzian M, Firestone BA, Moxley BC. pH controlled release from hydrophobic polyelectrolyte copolymer hydrogels. J Contr Rel 1988; 8:179–182.
[14]. J. Saminathan, A. S. K Sankar, K. Anandakumar, T.Vetrichelvan; Simple UV Spectrophotometric Method for the Determination of Fluvastatin Sodium in Bulk and Pharmaceutical Formulations; E-Journal of Chemistry 2009, 6(4), 1233-1239
R e f e r e n c e s
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