Dear Joanne,

For the formation of gel beads you need to use calcium ion or other divalent ions. This is because sodium and potassium alginate (monovalent alginate) is a water soluble compounds thus inhibits the formation of gel beads whereas calcium alginate (divalent alginate) is insoluble in water.

For more on this, please read the following text:

Alginate is a water-soluble linear, polyanionic; polysaccharide extracted from brown seaweed and is composed of alternating blocks of 1-4 linked α-L-guluronic and β-D-mannuronic acid residues. The gel beads are prepared through the sol-gel transformation of alginate which is brought about by cross-linking the alginate with divalent cations like Ca 2+ , Zn 2+ . Guluronic acid is responsible for the formation of gel by the alginate with the cations in the solution. The alginate matrix consisting of an open lattice structure forms porous beads. The beads have low retention capacity for encapsulating low molecular weight and water soluble drugs. 

Chitosan is a biocompatible, biodegradable, nontoxic, linear co-polymer polysaccharide, consisting of β (1-4)-linked 2-amino-2-deoxy-D-glucose (D-glucosamine) and 2-acetamido-2-deoxy-D-glucose (N-acetyl-D-glucosamine) units and has the structural similarity to cellulose (made up of β (1-4)-linked D-glucose units). Chitosan is the N-deacetylated derivative of chitin, although this N-deacetylation is never complete, which has a number of amino groups exposed making it polycationic polysaccharide. Depending on the amount/extent of deacetylation, different grades of chitosan are found. Due to its gel-forming property, it has been used in the designing of drug delivery system.

The more effective beads for the drug delivery can be formed by using the combination of both alginate and the chitosan. The interaction between alginate and chitosan has been systematically investigated. Their polyelectrolyte complex has been widely used to obtain devices for the controlled release of drugs. [4] The interaction between the alginate and the chitosan forms the polyelectrolyte complex via the ionic interaction between the carboxyl residue of alginate and the amino residue of chitosan. The complexation of alginate with chitosan decreases the leakage of the encapsulated drug from the beads. Due to this reason, the previously used alginate beads and the chitosan-tripolyphosphate beads which had low mechanical strengths are replaced by the alginate chitosan beads which can be prepared by various methods.

Preparation Method:

Ionotropic gelation method

This includes the formation of the hydrogel beads by treating the alginate solution with the solution containing polyvalent (mostly divalent) ions. The polyvalent ions help in the formation of the gel by forming a bond with the alginate. This is the commonest method employed and it can be modified in many different ways to bring about the desired shape, size, and therapeutic effects. 

The solution of the sodium alginate is prepared (different concentration). To that solution, the drug (if required in suitable vehicle) in different concentrations is added. The mixture is stirred and allowed to stand for required time. The mixture is then dropped into the solution containing divalent ion (different concentration) and if required at different pH conditions. The beads thus formed are washed (different solutions) and dried (different conditions). The wet beads thus formed can then be coated with the polymers like chitosan and then dried to modify the release. The solution of sodium alginate is mixed with the drug solution and the polymer like chitosan is added to it. Then the mixture is gelled with divalent ion solution as above. Further modification can be the addition of the alginate solution into the mixture of divalent ion salt and the polymer (chitosan). Then the beads formed are passed through the same processes.

References & Links:

George M, Abraham TE. Polyionic hydrocolloids for the intestinal delivery of protein drugs: Alginate and chitosan - A review. J Control Release. 2006;114:1-14 Back to cited text no. 2

Wong TW, Chan LW, Kho SB, Heng PWS. Design of controlled release solid dosage forms of alginate and chitosan using microwave. J Control Release 2002;84:99-114 Back to cited text no. 3

Xu Y, Zhan C, Fan F, Wang L, Zheng H. Preparation of dual crosslinked alginate-chitosan blend gel beads and in vitro controlled release in oral site-specific drug delivery system. Int J Pharm 2007;336:329-37 Back to cited text no. 4

Poncelet D, Babak V, Dulieu C, Picot A. A physico-chemical approach to production of alginate beads by emulsification-internal ionotropic gelation. Colloids Surfaces A: Physicochem Engineering Aspects 1999;155:171-6. Back to cited text no. 5

Shu XZ, Zhu KJ. The release behavior of brilliant blue from calcium alginate gel beads coated by chitosan: The preparation method effect. Eur J Pharm Biopharm 2002;53:193-201. Back to cited text no. 6

Murata Y, Toniwa S, Miyamoto E, Kawashima S. Preparation of alginate gel beads containing chitosan salts and their function. Int J Pharm 1999;176:265-8. Back to cited text no. 7

Murata Y, Toniwa S, Miyamoto E, Kawashima S. Preparation of alginate gel beads containing chitosan nicotinic acid salts and their functions. Eur J Pharm Biopharm 1999;48:49-52. Back to cited text no. 8

Murata Y, Kontana Y, Ohmae H, Kawashima S. Behavior of alginate gel beads containing chitosan salts prepared with water soluble vitamins. Eur J Pharm Biopharm 2002;53:249-51.

http://www.cysonline.org/article.asp?issn=2229-5186;year=2011;volume=2;issue=4;spage=192;epage=196;aulast=Bhattarai

http://www.bioline.org.br/pdf?pr09056

http://www.physics.uoguelph.ca/psi/papers/Bacteria%20%26%20Biofilms/Bacteria_EPS%26LPS/Gotoh_Chemosphere_03.pdf

http://www.scielo.br/pdf/bjps/v46n4/21.pdf

Hoping this will be helpful,

Rafik

According to my previous work, alginate form a gel with divalent cations like Calcium via producing insoluble complex which occur due to the chelation of COO_ groups to the    Ca++ as a central atom , this model is known as an egg box model. Incontract, the monovalent cations such as Na+ could not form such complex because of the solubility and charge reasons

Thanks a lot Sir Rafik Karaman and Sir Fateh Eltaboni for your detailed and clear explanation. They are very helpful and understandable. Yet, I still have question regarding this:

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There are 2 methods of preparation:

1. 1 way preparation: mixed drug and alginate dropped into solution containing  chitosan AND calcium cloride (Ca2+ as divalent ion) solution

2. 2 way preparation, as Sir Rafik Karaman mentioned before: "The mixture is then dropped into the solution containing divalent ion (different concentration) and if required at different pH conditions. The wet beads thus formed can then be coated with the polymers like chitosan and then dried to modify the release."

If the preparation follows the first method, will chitosan bond with Ca2+ ONLY (as chitosan has also many negative-charged-group), instead of bond with alginate and Ca2+, together, forming ca alginate beads with chitosan layer?