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)

Quick View

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

[5]. P. Akkas, M. Sar, M. S en, O. GuÈ ven; The effect of external stimuli on the Bovine Serum Albumin adsorption capacity of poly(acrylamide/maleic acid) hydrogels prepared by gamma rays; Radiation Physics and Chemistry 55 (1999) 717±721 [6]. Milen Dimitrov, Nikolai Lambov, Stoicho Shenkov, Veneta Dosseva, Vladimir Y. Baranovski; Hydrogels based on the chemically crosslinked polyacrylic acid: Biopharmaceutical characterization; Acta Pharm. 53 (2003) 25–31 [7]. Mohammad Asif, Mohd Yasir, Arundhati Bhattacharya and Meenakshi Bajpai; Formulation And Evaluation Of Gastroretentive Dosage Form For Fluvastatin Sodium; International Journal Of Comprehensive Pharmacy ISSN 0976-8157

[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.

[9]. G. M. McGeehan, D. M. Bickett, M. Green, D. Kassel, J. S. Wiseman, and J. Berman. Characterisation of the peptide substrate specificities of interstitial collagenase and 92-kDa gelatinase—implications for substrate optimization. J. Biol. Chem. 269:32814–32820 (1994).

[10]. T. A. Holland, Y. Tabata, and A. G. Mikos. Dual growth factor delivery from degradable oligo(poly(ethylene glycol) fumarate) hydrogel scaffolds for cartilage tissue engineering. J. Control. Release. 101:111–125 (2005). doi:10.1016/j.jconrel.2004.07.004.

[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

Thank you…

Thank you…

Thank you…

Thank you…

Thank you…

Thank you…

Thank you…