Central Salt & Marine Chemicals Research Insitute,

Bhavnagar

Fortification of edible salt- CSMCRI Technologies

Dr.J.R.Chunawala, Principal Scientist,

CSIR-CSMCRI

Jan 2016

Micronutrient deficiency

• Iron deficiency is the most common micronutrient deficiency in the

world affecting 2 billion people, 2 billion nearly people have

inadequate iodine nutrition, and approximately 250 million preschool

children are vitamin A deficient.

• About 2/3rd of under 5 years children, more than ½ of women in

reproductive ages including adolescents and pregnant women are

anaemic (NFHS- 3, 2005-06)

• Significantly higher prevalence in SC /ST population /clusters

• Micronutrient deficiencies account for about 7.3% of the global burden

of diseases.

• As per WHO, India falls under the category of severe public health

significance. (>40% Anaemia prevalence)

• Micronutrient deficiencies place a heavy burden on the health and

economy of nation

• 11 % Gross Domestic Product (GDP) lost in Asia and Africa as a result

of under nutrition

CSIR-CSMCRI

Recommended daily minimum requirements of some essential elements

Age (year)

Ca

(mg)

P

(mg)

I

(g)

Fe

(mg) Mg (mg)

Zn

(mg) Cu (mg)

Mn

(mg)

Infants 0 – 0.5 500 750 90 0.27* 30 3 0.6 0.6

0.5 – 1.0 500 750 90 05 45 5 0.6 0.6

Children 1 – 3 600 600 90 9 50 5 1.0 1.0

4 – 6 600 600 90 13 70 7 1.5 1.5

7 – 10 600 600 120 16 100 8 1.5 1.5

Males 11 – 14 800 800 150 21 120 9 2.0 4.0

15 – 18 800 800 150 27 195 11 2.0 4.0

19 – 22 800 600 150 17 340 12 2.0 4.0

23 – 50 800 600 150 17 340 12 2.0 4.0

51+ 800 600 150 17 340 12 2.0 4.0

Females 11 – 14 800 800 150 27 160 9 2.0 4.0

15 – 18 800 800 150 27 235 12 2.0 4.0

19 – 22 800 600 150 21 310 10 2.0 4.0

23 – 50 800 600 150 21 310 10 2.0 4.0

51+ 800 600 150 21 310 10 2.0 4.0

Pregnant

women 1200 1200 200 35 310 12 2.0 4.0

Lactating

mother 1200 1200 200 25 310 12 2.0 4.0

anaemia prevalence in Indian women

Iodine, Iron, Zinc, Vitamin A, Calcium,

Vitamin D, Vitamin B12, Folic acid

Micronutrient deficiency occur concurrently

IODINE DEFICIENCY

In India, household coverage of adequately

iodized salt (83.2% in urban areas vs. 66.1% in

rural areas)

350 million people are at risk of IDD as they

consume salt with inadequate iodine.

Every year nine million pregnant women and

eight million newborns are at risk of IDD in

India.

Salt as a Carrier of Nutrients

Uniform consumption levels within a country/region

Cost

Well distributed in all food preparations

potential to quickly reach large populations without socio-economic

barriers

low potential for excessive intake

Double fortified salt is an innovative new concept of fortified food

product – deliver small but required amounts of iodine and iron to human

body through diet

The major problem is the interaction between iodine and iron which results

in a loss of iodine.

Selection of Iodine Compound

Name Chemical

Formula

%

Iodine

Mol.

Wt.

M.P. 0C

B.P. 0C

Solubility in Water (g/L)

00C 200C 300C 400C 600C

Iodine I2 100 253.8 113 184 - - 0.3 0.4 0.6

Calcium

Iodide CaI2 86.5 293.9 740 1100 646 676 690 708 740

Calcium

Iodate Ca(IO3)26H2O 65.0 498 35 - - 1.0 4.2 6.1 13.6

Potassium

Iodide KI 76.5 166.0 686 1330 1280 1440 1520 1600 1760

Potassium

Iodate KIO3 59.5 214.0 560 d. 47.3 81.3 117 128 185

Sodium

Iodide NaI 2H2O 85.0 149.9 651 1304 1590 1790 1900 2050 2570

Sodium

Iodate NaIO3 64.0 197.9 d. - - 25.0 90.0 150 210

Loss of iodine in iodised salt

Iodide oxidation and iodate reduction leads to the formation of iodine:

2I- → I2 + 2e- ( oxidation )

2I5+ + 10e- → I2 ( reduction )

Solar sea salt contains magnesium and calcium chlorides as impurities, hydrolysis of

these salts in water produces an acid:

MgCl2 → Mg(OH)Cl + HCl ( in presence of H2O)

MgCl2 → MgO + 2HCl( in presence of H2O)

Decomposition of iodide or iodate :

4I- + O2 + 4 H+→ 2I2 +2H2O (presence of acid, sunlight and oxygen)

IO3- + 5I- +6H+→ 3I2 +2H2O ( at elevated temperature)

IO3- + 6 Fe2+ + 6 H+ → I- + 6 Fe3+ + 3H2O

IO3- +5I- + 6H+ →3I2 + 3H2O

Fe3+ + 2I- → 2Fe2+ + I2

CSIR-CSMCRI

Demonstration of iodine loss by heating the mixture

of moist KIO3 (1 g) and MgCl2.6H2O on a sand bath

CSIR-CSMCRI

Demonstration of iodine liberation by heating

KIO3 with tamarind and 2-3 drops of water

CSIR-CSMCRI

Iodine Estimation Kit for Iodized Salt

CSIR-CSMCRI

CSMCRI Iodizing agent with improved stability

Key innovation:

• Reaction of iodine crystals and aq.alkali generates iodide –iodate couple in 5: 1 mole ratio and the use of resultant solution for preparation of iodized salt.

• Gastric juice would convert the latent iodine into its elemental form – more facile absorption by body.

• Process easier and cost effective .

US Patent Application No. 20110008497

Canadian Patent No. 6,27,154

Preparation of iodising agent:

3 I 2 +6 OH - → 5 I - +IO3 - +3 H 2 O

Exposure to Stomach condition:

IO 3 - +5 I -+6 H + → 3 I 2 +3 H 2 O

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

0 3 6 12 16 18 24 30 36 40 46 48

Iod

ine

, p

pm

Months

CSIR-CSMCRI

CSMCRI- ultra stable iodizing agent

US Patent No .7695707, April, 2010 ,EP No. 1,575,874

US Patent Appl. No. 20090188810

PCT Appl. No. PCT/IN2004/000405, Pub. No. WO/2006/067798

Anion exchange reaction:

Mg (1 - x) Al x (OH) 2 (Basic Layer)

(Inter Layer)

(Basic Layer) Mg (1 - x) Al x (OH) 2

H 2 O CO 3 2 - H 2 O + 2IO 3

-

Mg (1 - x) Al x (OH) 2

Mg (1 - x) Al x (OH) 2

H 2 O 2 IO 3 - H 2 O

* exchangeable x – 0.20 - 0.33

Anion exchange reaction:

Mg (1 - x) Al x (OH) 2 (Basic Layer)

(Inter Layer)

(Basic Layer) Mg (1 - x) Al x (OH) 2

H 2 O CO 3 2 - H 2 O + 2IO 3

-

Mg (1 - x) Al x (OH) 2

Mg (1 - x) Al x (OH) 2

H 2 O 2 IO 3 - H 2 O

* exchangeable x – 0.20 - 0.33

CSMCRI

0

5

10

15

20

25

30

35

0 10 20 30 40 50 60 70

Iod

ine

(pp

m)

No. of Months

Stability Data

Magnesium aluminum hydroxide Octahedral

forms positively charged layers and balancing

anionic carbonate ions are located between the

layers as interlayer anions.

Basic Magnesium Aluminum Hydroxy Carbonate

Hydrate

Key Innovations

Process for preparation of stable iodizing agent with proven

performance.

Process simplicity and economy in iodate consumption.

STL,Jaipury = 0.0074x + 31.099

R2 = 0.0659

0.00

10.00

20.00

30.00

40.00

0 50 100 150 200

No of Days

Iod

ine

in

pp

m

STL,Jaipur

Linear (STL,Jaipur)

STL,Tuticoriny = 0.0277x + 28.953

R2 = 0.6195

0.00

10.00

20.00

30.00

40.00

0 50 100 150 200

No of Days

Iod

ine

in

pp

m

STL,Tuticorin

Linear (STL,Tuticorin)

STL,Bhubneshwary = 0.0123x + 31.601

R2 = 0.1949

0.00

10.00

20.00

30.00

40.00

0 50 100 150 200

No of Days

Iod

ine

in

pp

m

STL,Bhubneshwar

Linear

(STL,Bhubneshwar)

S.N0.No Of

DaysSTL,Jaipur STL,Tuticorin STL,Bhubneshwar

1 0 28.87 29.95 33.06

2 15 34.06 29.39 31.60

3 30 29.80 29.95 30.50

4 49 32.91 29.72 33.46

5 64 32.65 29.62 29.96

6 79 30.96 30.26 33.07

7 94 30.88 30.83 33.07

8 109 30.71 31.35 32.28

9 124 33.20 35.70 32.81

10 141 31.81 33.34 36.16

11 156 33.74 33.04 33.18

12 171 31.19 32.83 32.76

Iodine stability in iodised salt

Prepared using novel compound

- tested by Salt Department

CSIR-CSMCRI

KEY:

G=Good, F=Fair, P=Poor,

-=Information not available

R=Recommended, V=Variable,

NR=Not Recommended

% Iro

n C

on

tent

Bio

availa

bility

in H

um

an

s

Bio

availa

bility

in A

nim

als

Salt

Rela

tive co

st

facto

r

Freely water soluble

Ferrous sulphate 7H2O 20 G G V 5.0

Ferrous gluconate 12 G G V 8.3

Ferrous lactate 19 G G NR 5.3

Ferric ammonium citrate 18 G G NR 5.5

Ferrous ammonium sulphate 14 - G - -

Ferric choline citrate 14 - G NR -

Slowly Soluble

Dried Ferrous Sulphate 33 G G V 3.0

Ferric glycerophosphate 15 G G NR 6.6

Ferric citrate 17 P V 17.6

Ferric sulphate 22 P G NR 13.6

Ferric saccharate 3-35 F G - 5.7-6.6

Ferric chloride 34 F G NR 5.9

Poorly Soluble

Ferrous fumarate 33 G G R 3.0

Ferrous succinate 35 G G - 2.8

Ferrous tartrate 22 F F - 9.0

Ferrous citrate 24 F F V 8.4

Almost insoluble or soluble

Ferric pyrophosphate 25 P P R 12.0

Ferric orthophosphate 28 P P R 10.7

Sodium iron pyrophosphate 15 P P NR 20.0

Reduced elemental iron

a. reduced by hydrogen 96 F F NR 2.1

b. reduced by carbon monoxide 96 F F NR 2.1

c. Carbonyl Iron 98 F F NR 2.1

d. Reduced by electrolysis 97 F F NR 2.1

Ferric oxide 70 P P NR 4.2

Ferric hydroxide 62 P P NR 4.8

Ferrous carbonate 35 P P NR 8.5

Iron complex compound

Sodium ferric EDTA 13 G G - 7.7

Commercially available Iron Compounds

Relative cost factor

= 100 x bioavailability factor in human / % of iron

Bioavailability factor

= G(1) ; F (2); P (3)

Types of

DFS

Iron Compound

(1000 ppm)

Iodine

Compound

(40ppm)

Additives In-Vitro

Results

In-Vivo

Results

Clinical

Trial

Results

Type 1

Ferrous Fumarate

(Diosady, 2002)

(Encap.)

KIO3 Soy Stearine, TiO2,

SHMP Unknown Unknown Unknown

Type 2

Ferrous Sulphate

Heptahydrate

(Shivkumar, 2001)

KIO3

(Encap.) SHMP Unknown Yes Unknown

Type 3

Ferrous Sulphate

Monohydrate

(Encap.)

KIO3

(Encap.)

Malic acid, SHMP,

Sodium dihydrogen

phosphate, NaHCO3

Unknown Unknown Unknown

Type 4

Ferrous Sulphate

hydrate

(Encap.)

KIO3

Cellulose acetate

phthalate, Silicon,

Partially hydrogenated

vegetable oil

Unknown Unknown Unknown

Type 5

Ferric

Pyrophosphate

(FePP)

(Micronized)

KIO3 Yes Yes Unknown

Type 6 Sodium Ferric

EDTA KIO3

Stabilizers, Colour

masking agent Unknown Unknown

Unknown

CSIR

CSMCRI

Inorganic iron

( premix)

IO3-

( premix) No additives Known Known Unknown

Characterisation of the most recent produced formulation by type of

Double Fortified Salt (DFS)

CSMCRI - Double fortified salt ( DFS)using novel Iron

fortifying agent

Key Innovations

Use of waste bittern as magnesium source

Aluminum is replaced by Fe

White in colour

Prevented chemical interaction between iron and

iodine in salt medium

Safe ,affordable, stable, used without compromising

appearance, stability, taste, and texture of the salt

Process simplicity.

A white coloured synthetic hydrotalcite of approximate formula

[Mg4.1±0.4Fe(III)(OH)10.2±0.7][CO3]0.5 .3H2O], as iron source for iron fortification.

Fortification of edible salt with a novel iron fortifying agent and iodizing agent has been developed

prepared cost effectively using synthetic hydrotalcite.

Process has been scaled up and optimized (30 gm to 3 kg) for fortifying agent)

CSIR-CSMCRI

Bioavailability and toxicity studies of DFS

The bioavailability study has been initiated with Govt. Medical college,

Bhavnagar. Prof. C.B.Tripathi, Head, Pharmacology Deptt, is carrying out the

study for which CSMCRI will give the DFS salt samples and assist in in vitro

study and they will help in in vivo studies( rats and human ).

CSIR-CSMCRI

Group Type of salt Initial

(Hb)

After

depletion

(6 months)

(Hb)

After repletion

(1 month period)

(Hb)

II Salt with

Ferrous

sulphate

12 - 15 11 - 12 14 - 14.6

III Common salt

( No Fe)

13.7 - 14.6 12.4 - 14 13.5 - 14.2

IV DFS-CSMCRI 12.9 – 15.1 12 – 13.5 14 – 18

I DFS-CSMCRI 13.9-14.6 12.8-14.4 Cont.- 8 months

13.3- 18.5

Preliminary studies of bioavailability tested at Department of Pharmacology,

Government Medical college, Bhavnagar, using wistar rats.

The results indicated clearly that the iron contained in DFS prepared by this institute is more effective

than the other conventional iron fortified salt

Bioavailability of the iodine have been be conducted at Department of Pharmacology, Government

Medical college, Bhavnagar using 50 wistar rats and results are awaited.

The cost of fortification for fortifying salt to contain 1000 ppm of iron and 30 ppm of iodine works

out to be Rs. 1.5 per kg of salt.

Bioavailability of iron and iodine in Double Fortified Salt

CSIR-CSMCRI

CSIR-CSMCRI patents on salt fortification

1. Iodizing agent and process for preparation thereof

International Application No.PCT /IN 2004 /000190 ,Granted on 13 th April,2010,

US patent No. 7695707

2. Process for the Preparation of Stable Iodate-Exchanged Synthetic Hydrotalcite

with Zero Effluent Discharge.

International Application No.PCT /IN 2008 /000615 Granted on 14 th August ,2012, US patent

No. US 8,241,483 B2

3. Iodized salt and a process for its preparation.

International Application No. PCT/IN2004/000405, Pub.No. WO/2006/067798

Granted on 14 th May ,2010, US patent No. US 8,440,252

4. Novel double fortified salt compositions containing iron and iodine and process of

preparation thereof.

International Publication Number WO 2013/128474 A1, publication date 6th Sept. 2013.US patent

publication No.US2015/0037466 A1,5 th Feb.2015

The cost of fortification for fortifying salt to contain 1000 ppm of iron and 30 ppm of

iodine works out to be Rs. 1.5per kg of salt.

CSIR-CSMCRI

MOU with District Administration

THANK YOU CSIR-CSMCRI