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P R E PA R AT I O N   A N D C H A R A C T E R I S AT I O N O F
H Y D R O G E L B A S E D D RU G D E L I V E RY S Y S T E M F O R
           R E L E A S I N G F LU VA S TAT I N D RU G

                     Under the guidance of
                      Dr. Smita Mohanty



                         Mohamed Adam.K
                         (Reg.No.1007108017)
Quick View
Fluvastatin : Works against Hypercholesterolemia

            Fluvastatin is a competitive inhibitor of
 HMG-CoA reductase, whichmechanism is afor the conversion
  The ultimate result of this is responsible reduction of the
  of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to
   plasma total cholesterol which is responsible for coronary
  Shorter biological half life (2.5 hrs ) and Poor bioavailability
    mevalonate, a precursordisease (CAD)
                      artery of sterol, including cholesterol.
         (20%) has necessitated the administration of
     repeated (20 to o u n twice a dayh and W o rdoses
        B a c k g r 40 mg d o f t ) e higher k
 to obtain the desired therapeutic efficacy which often leads
    Administration of statins by oral rout is associated with
                        to risk of toxicity.
several problems including diarrhea, constipation, indigestion
         and does not usually provide rate-controlled
                  release or target specificity.

                Structural formula for fluvastatin
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. rTheir abilitya v i n g h i g h
  A c r y l i c b a s e d h y d o g e l s h to swell, under
  c h aphysiological conditions, o t h athemn y ideal e r
        r g e t o m a s s r a t i makes n a an o t h
              material forp o l y m e r s
                           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.
Impregnation of Hydrogel with drugs




Preparation of Drug Loaded Hydrogel
Materials
       Acrylic acid
       N,N-methylenebisacrylamide (MBA) - Cross linker
       Ammoniumpersulfate (APS) - An Initiator
       N,N,N,N’-tetramethylethylenediamine
                        (TEMED) - An Accelerator
       Sodium hydroxide (NaOH) - Neutralizer
  Preparation of PSA 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.
Spectral Characterization of PSA Hydrogel
        110
        110   0 .4 % g e l
              Stoc k s oln



        100
        100
         90

         90
         80

         80
         70




                                                                                                                                                               1355. 6




                                                                                                                                                                                                    962. 1
                                                                                                                                                                                      1060. 5
                                                                                          1657. 8
         60




                                                                                                                                        1454. 0


                                                                                                                                                            1313. 5
         70




                                                                                                                                                                                                992. 6
                                                                                                    1646. 1
         50




                                                                                                                                                                           1276. 0
         60
   %T




                                                                                                                                                  1402. 5
         40




                                                                                                                                                                                                             835. 7
         50
         30



                 Results and Discussion



                                                                                                              1636. 7
                                              3243. 5




                                                                                                                         1540. 7
         40
         20




                                                                                                                                                                 1350. 9
                                                                                                                                                    1425. 9
         30
         10
                                    3316. 1




          0




                                                                                                                              1536. 0
         20

        -10
         10
        -20
         4000                3500
                             3500                       3000
                                                        3000   2500
                                                                2500             2000
                                                                                  2000                                  1500
                                                                                                                         1500                                                        1000
                                                                                                                                                                                      1000                            500
                                                                                                                                                                                                                       500
                                                                   Wavenum bers (c m-1)
                                                                   Wavenum bers (c m-1)




                             FTIR Spectra of of stock solutiongel
                               FTIR Spectra crosslinked PSA
        When sodium acrylate is polymerized the C=C bond is
    1640 cm-1, bond. This the C=C captured in the FTIR spectra
converted to C–C related towas clearlyacrylate stretch mode ; as
      the size of the1420 cm-1, peak at 1645C–C. reduced with
                      absorption related to cm-1
                      progress of polymerization.
Effect of Crosslinker Concentration

                                  2500


                                  2000

                                                                            0.2% CL
             Swelling ratio (%)

                                  1500
                                                                            0.4% CL

                                  1000                                      0.8% CL

                                                                            1% CL
                                   500


                                     0
                                         0   100      200       300   400

                                                   Time (min)




   Swelling behavior of Poly(sodium acrylate) hydrogels
with different crosslinker concentration in distilled water at
                     room temperature.
Effect of pH on Swelling Ratio


                   1800.00

                   1600.00
                                                                            pH=2
                   1400.00                                                  pH=3
                                                                            pH=4
                   1200.00                                                  pH=5
                                                                            pH=6
            Swelling Ratio %




                   1000.00                                                  pH=7

                               800.00

                               600.00

                               400.00

                               200.00

                                 0.00
                                     0.00   500.00      1000.00   1500.00   2000.00


                                                     Time (min)



Swelling behavior of Poly(sodium acrylate) hydrogels at different pH
Conformation of Fluvastatin Loading




FTIR Spectra of drug loaded PSA gel
FTIR Spectra of crosslinked PSA gel
Effect of Incubation Time on Drug Loading




The dependency of the drug loading amount on the
                incubation time
Effect of Amount of Crosslinker on Drug Loading




The dependency of the drug loading amount to the
           crosslinker concentration
Drug Release as a Function of Time




Release of fluvastatin from hydrogel carrier
            as a function of time
Po l y ( s o d i u m a c r y l ate ) hyd ro ge l s wa s sy nt h e s i ze d
t h ro u g h c ro s s l i n k i n g o f a c r y l i c a c i d / a c r y l a m i d e .
Swe l l i n g ca p a c i t y o f t h e hyd ro ge l s i s a ffe c te d b y
t h e c ro s s l i n ke r ( M BA ) co n c e nt rat i o n , s o t h at t h e
   s we l l i n g i s d e c re a s e d b y i n c re a s i n g t h e M BA
                           Conclusion
  co n c e nt rat i o n . T h e s u p e ra b s o r b e nt hyd ro ge l s
ex h i b i te d h i g h s e n s i t i v i t y to p H , s o t h at , s e ve ra l
s we l l i n g c h a n ge s o f t h e hyd ro ge l we re o b s e r ve d
     i n p H va r i at i o n s o f a w i d e ra n ge ( 2 - 7 ) a n d
           effe c t i ve e n o u g h fo r d r u g d e l i ve r y.
References
Thank you…    Thank you…


       Thank you…
    Thank you…
       Thank you…
Thank you…
                Thank you…

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Hydrogel Drug Delivery System

  • 1. P R E PA R AT I O N A N D C H A R A C T E R I S AT I O N O F H Y D R O G E L B A S E D D RU G D E L I V E RY S Y S T E M F O R R E L E A S I N G F LU VA S TAT I N D RU G Under the guidance of Dr. Smita Mohanty Mohamed Adam.K (Reg.No.1007108017)
  • 3. Fluvastatin : Works against Hypercholesterolemia Fluvastatin is a competitive inhibitor of HMG-CoA reductase, whichmechanism is afor the conversion The ultimate result of this is responsible reduction of the of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to plasma total cholesterol which is responsible for coronary Shorter biological half life (2.5 hrs ) and Poor bioavailability mevalonate, a precursordisease (CAD) artery of sterol, including cholesterol. (20%) has necessitated the administration of repeated (20 to o u n twice a dayh and W o rdoses B a c k g r 40 mg d o f t ) e higher k to obtain the desired therapeutic efficacy which often leads Administration of statins by oral rout is associated with to risk of toxicity. several problems including diarrhea, constipation, indigestion and does not usually provide rate-controlled release or target specificity. Structural formula for fluvastatin
  • 4. 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. rTheir abilitya v i n g h i g h A c r y l i c b a s e d h y d o g e l s h to swell, under c h aphysiological conditions, o t h athemn y ideal e r r g e t o m a s s r a t i makes n a an o t h material forp o l y m e r s 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.
  • 5. Impregnation of Hydrogel with drugs Preparation of Drug Loaded Hydrogel
  • 6. Materials Acrylic acid N,N-methylenebisacrylamide (MBA) - Cross linker Ammoniumpersulfate (APS) - An Initiator N,N,N,N’-tetramethylethylenediamine (TEMED) - An Accelerator Sodium hydroxide (NaOH) - Neutralizer Preparation of PSA 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.
  • 7. Spectral Characterization of PSA Hydrogel 110 110 0 .4 % g e l Stoc k s oln 100 100 90 90 80 80 70 1355. 6 962. 1 1060. 5 1657. 8 60 1454. 0 1313. 5 70 992. 6 1646. 1 50 1276. 0 60 %T 1402. 5 40 835. 7 50 30 Results and Discussion 1636. 7 3243. 5 1540. 7 40 20 1350. 9 1425. 9 30 10 3316. 1 0 1536. 0 20 -10 10 -20 4000 3500 3500 3000 3000 2500 2500 2000 2000 1500 1500 1000 1000 500 500 Wavenum bers (c m-1) Wavenum bers (c m-1) FTIR Spectra of of stock solutiongel FTIR Spectra crosslinked PSA When sodium acrylate is polymerized the C=C bond is 1640 cm-1, bond. This the C=C captured in the FTIR spectra converted to C–C related towas clearlyacrylate stretch mode ; as the size of the1420 cm-1, peak at 1645C–C. reduced with absorption related to cm-1 progress of polymerization.
  • 8. Effect of Crosslinker Concentration 2500 2000 0.2% CL Swelling ratio (%) 1500 0.4% CL 1000 0.8% CL 1% CL 500 0 0 100 200 300 400 Time (min) Swelling behavior of Poly(sodium acrylate) hydrogels with different crosslinker concentration in distilled water at room temperature.
  • 9. Effect of pH on Swelling Ratio 1800.00 1600.00 pH=2 1400.00 pH=3 pH=4 1200.00 pH=5 pH=6 Swelling Ratio % 1000.00 pH=7 800.00 600.00 400.00 200.00 0.00 0.00 500.00 1000.00 1500.00 2000.00 Time (min) Swelling behavior of Poly(sodium acrylate) hydrogels at different pH
  • 10. Conformation of Fluvastatin Loading FTIR Spectra of drug loaded PSA gel FTIR Spectra of crosslinked PSA gel
  • 11. Effect of Incubation Time on Drug Loading The dependency of the drug loading amount on the incubation time
  • 12. Effect of Amount of Crosslinker on Drug Loading The dependency of the drug loading amount to the crosslinker concentration
  • 13. Drug Release as a Function of Time Release of fluvastatin from hydrogel carrier as a function of time
  • 14. Po l y ( s o d i u m a c r y l ate ) hyd ro ge l s wa s sy nt h e s i ze d t h ro u g h c ro s s l i n k i n g o f a c r y l i c a c i d / a c r y l a m i d e . Swe l l i n g ca p a c i t y o f t h e hyd ro ge l s i s a ffe c te d b y t h e c ro s s l i n ke r ( M BA ) co n c e nt rat i o n , s o t h at t h e s we l l i n g i s d e c re a s e d b y i n c re a s i n g t h e M BA Conclusion co n c e nt rat i o n . T h e s u p e ra b s o r b e nt hyd ro ge l s ex h i b i te d h i g h s e n s i t i v i t y to p H , s o t h at , s e ve ra l s we l l i n g c h a n ge s o f t h e hyd ro ge l we re o b s e r ve d i n p H va r i at i o n s o f a w i d e ra n ge ( 2 - 7 ) a n d effe c t i ve e n o u g h fo r d r u g d e l i ve r y.
  • 16. Thank you… Thank you… Thank you… Thank you… Thank you… Thank you… Thank you…