Hydrogels of Solid lipid Nanoparticles of CurcuminPresented by

RUCHI CHAWLA ASSISTANT PROFESSOR

IIT(BHU), VARANASI

5th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems

March 16-18, 2015 Crowne Plaza, Dubai, UAE

Contents Introduction Experimental work

Preparation of SLNs Analytical Method for Curcumin Formulation characterization

Summary and conclusion References

IntroductionHydrogels:

Advantages of Hydrogels (Kopecek, 2009):

Shape stability and softness similar to that of the soft surrounding tissues

Chemical and biochemical stability

Absence of extractables

High permeability for water-soluble nutrients and metabolites across the biomaterial tissue-interface

Convenient handling

Easy application

Excellent tissue biocompatibility due to their high water content

Curcumin Yellow spice derived from the roots, rhizome of Curcuma longa Adaptogen, bio-protectant, anti-bacterial, antioxidant and anti-inflammatory Chemically it is a mixture of three principal compounds (Strimpakos and Sharma, 2008):

Curcumin (sometimes referred to as curcumin I), Demethoxycurcumin (curcumin II), and Bisdemethoxycurcumin (curcumin III)

Limitations: Poor systemic bioavailability because of poor absorption and rapid systemic

elimination via glucuronidation (Aggarwal and Sung, 2009). Hydrophobic compound with a high partition coefficient of 3.2 and water solubility

around 0.6 μg/ml (Kurien et al.,2007 and Patel et al., 2009).

Why Solid lipid Nanoparticles? Small size Possibility of controlled rug release Increased drug stability High drug pay load Incorporation of lipophilic and hydrophilic drugs Biocompatibility Enhancement of bioavailability of the incorporated drugs (Mehnert and Mader, 2001) Enhanced penetration of drug into the skin from lipid nanoparticles, occlusion effect and film

formation of lipid nanoparticles on the skin Larger surface area and contact point to adhere to the skin layer than that of microparticle. SLN can provide benefits of accumulation of drug in the skin strata to various skin diseases

such as acne and eczema (Korting et al, 2007).

Experimental Work

Preparation of SLNs of Curcumin by nanoprecipitation method (Chorny et al., 2002)

Injected slowly with stirring at 1000 rpm

Ultracentrifugation at 10,000 x g for 5 min

Solvent removal by evaporation room temperature for 24hours

UV spectrophotometric method for Curcumin

Characterization of SLNs

Compatibility studies

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0

5

10

15

20

25

30

35

40

45

%T

3508

.63

1627

.97

1508

.38 14

29.3

0

1280

.78

1205

.55

1153

.47 11

14.8

9

1026

.16

962.

51

856.

4280

8.20

466.

79

curcumin5007501000125015001750200022502500275030003250350037504000

1/cm

0

5

10

15

20

25

30

35

40

%T

2916

.47

2848

.96

2661

.85

1705

.13 14

64.0

214

33.1

6

1298

.14

937.

44

719.

4768

6.68

547.

80

stearic acid

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2.5

5

7.5

10

12.5

15

17.5

20

22.5

25

27.5

%T35

10.5

6

2918

.40

2848

.96 17

01.2

7

1627

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stearic acid + curcumin

FT-IR Spectrum of Curcumin + Stearic acid

FT-IR Spectrum of Stearic acidFT-IR Spectrum of Curcumin

Particle size and polydispersity of C-SLNs

Batches Particle-Size Poly Dispersity index

Batch-1 (0.5 % PVA) 697.7 + 0.06 nm -0.9375 + 0.0004

Batch -2 (0.75 % PVA) 939.8 + 0.01 nm 0.383+ 0.001

Batch 3 (1 % PVA) 527.6 + 0.04 nm -1.597+ 0.001

Entrapment Efficiency of C-SLNs

Batch (n=3) Total Drug content (mg) Free Drug Content (mg) Entrapment efficiency

(%EE)

(TDC –FDC)/TDC * 100)

Batch 1 5.448+ 0.02 1.006+ 0.07 81.53 + 0.02%

Batch 2 5.880+ 0.09 1.150+ 0.06 80.44 + 0.09%

Batch 3 5.860+ 0.10 1.012+ 0.07 82.73 + 0.01%

Hydrogel preparationS. No. Batches Carbopol concentration

(% w/v)Hydrogel type

1 B1 0.5 Blank gel

2 B2 1.0 Blank gel

3 B3 2.0 Blank gel

4 Y1 0.5 In-situ hydrogels*

5 Y2 1.0 In-situ hydrogels*

6 Y3 2.0 In-situ hydrogels*

7 D1 0.5 Enriched hydrogels^ (1:1 ratio of B2 and C-SLNs#)

8 D2 0.66 Enriched hydrogels (1:1 ratio of B2 and C-SLNs#)

*In situ hydrogels were prepared by adding carbopol (0.5, 1.0 and 2.0 %) to fixed volume of C-SLNs suspension containing 1% PVA^Enriched hydrogels were prepared by adding carbopol hydrogel (1%w/v) to # C-SLNs prepared using 1% PVA

Texture profile analysis

0 2 4 6 8 10 12 14

60

50

40

30

20

10

0

-10

-20

-30

-40

-50

Force (g)

Time (sec)

1 2 3

1F

2F

Y5

Typical force-time plot of Texture analysis

Texture analysis of blank hydrogels

Texture analysis of In-situ hydrogels

Texture analysis of In-situ hydrogels

Texture analysis of Enriched hydrogels

Comparative Texture analysis

Conducted using Franz diffusion cells and dialysis membrane Dissolution media: phosphate buffer pH 6.0 solution containing 1% v/v Methanol maintained at 37 ±

1 ◦C on a magnetic hot plate with moderate stirring

In-vitro release studies

In-vitro occlusion test

Summary & Conclusion Curcumin loaded SLNs were prepared by nano-precipitation technique using stearic acid as lipid and PVA as surfactant.

Batch-3 (1% PVA) exhibited particle size of 527.6 nm, PDI of -1.597 and % Entrapment efficiency 82.73% In vitro release from C-SLN enriched hydrogel showed controlled release of drug in comparison to C-SLNs upto 72

hr with approx.58 % release within 24 hours. Occlusion test showed reduced water loss from carbopol and even lesser from enriched hydrogel.

Stability studies over a period of 90 days, showed increase in firmness, cohesiveness and index of viscosity and decrease in consistency.

In-situ hydrogels exhibited a concentration (carbopol) dependent increase in firmness, consistency, cohesiveness and viscosity, however, presence of C-SLNs significantly decreased (p < 0.05) these values in comparison to blank hydrogels.

Similar observations were made in enriched hydrogels Also, a significant difference (p < 0.05) in hydrogel properties was observed between in-situ and enriched hydrogels

indicating effect of SLNs on the swelling properties of Carbopol. Occlusive properties of in-situ hydrogels were better than enriched and blank hydrogels. In-situ hydrogels also exhibited uniform and extended release of curcumin, alongwith higher permeation characteristics. Better formulation characteristics of in-situ hydrogels might be because of homogenous deposition and gelling of

carbopol around curcumin nanoparticles.

References: Strimpakos, A. S., Sharma, R. A. (2008). Comprehensive invited review curcumin: preventive and therapeutic properties in

laboratory studies and clinical trials. Antioxidants & Redox Signaling 10, 511-546.

Kurien, B. T., Singh, A., Matsumoto, H., Scofield, R. H. (2007). Improving the solubility and pharmacological efficacy of curcumin by heat treatment. Assay and Drug Development Technologies 5, 567-576.

Patel, R., Singh, S. K., Singh, S., Sheth, N.R., Gendle, R. (2009). Development and characterization of curcumin loaded transfersome for transdermal delivery. Journal of Pharmaceutical Sciences and Research 1, 71-80.

Aggarwal, B. B., Sung, B. (2009). Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends in Pharmacological Sciences 30, 85-94.

Mehnert, W. and Mader, K. (2001) Solid lipid nanoparticles: Production, characterization and applications. Adv. Drug Deliv. Rev., 47, 165-196.

Yang, S., Zhu, J., Lu, Y., Liang, B., Yang C. (1999) Body distribution of camptothecin solid lipid nanoparticles after oral administration. Pharm. Res., 16 , pp. 751–757.

Korting, M.S., Mehnert, W. and Korting, H.C. (2007) lipid nanoparticles for improved topical applicationof drugs for skin disease, Adv Drug Del Review, 59, 427-443.

Chorny, M., Fishbein, I., Danenberg, H.D., Golomb, G. (2002) Lipophilic drug loaded nanospheres prepared by nanoprecipitation: effect of formulation variables on size, drug recovery and release kinetics Journal of Controlled Release 83 389–400.

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