Evaluation of cyclodextrins for enhancing corneal penetration of natamycin eye drops

Abstract

A new group of pharmaceutical excipients called cyclodextrins can be introduced into ophthalmology for delivering such water insoluble drug. This group of excipients is able to solubilize many water insoluble drugs which were previously impossible to be formulated as aqueous eye drop solution by forming their inclusion complexes. Analysis of pure drug and excipients by physical test, melting point determination, chemical test and solubility determination were carried out in this study. It may be concluded that cyclodextrin complexes of Natamycin can lead to an aqueous formulation (Natamycin eye drop) having better trans corneal permeability and thus can be proved to have faster and better antifungal efficiency.

Eye drop formulations are aqueous solution. Drugs selected for ocular medication are those which are nonirritant and have the capacity to penetrate the cornea and conjunctiva. Drugs must reach the aqueous humor in order to act on the muscles of iris and ciliary epithelium.[1] Many drugs that are useful in topical application to the eye are not sufficiently water soluble. A new group of pharmaceutical excipients called cyclodextrins can be introduced into ophthalmology for delivering such water insoluble drug. This group of excipients is able to solubilize many water insoluble drugs which were previously impossible to be formulated as aqueous eye drop solution by forming their inclusion complexes. The cyclodextrins increase the water solubility of the drug and thus enhances the drug absorption into the eye. It improves aqueous stability of the drug and reduces local irritation.[2]

Materials and Methods

Analysis of pure drug and excipients

Physical test

Physical study is an important prerequisite before using any drug or excipient for in-vitro or in-vivo analysis. For this a small amount of the drug as well as the excipients were studied for their different parameter i.e. physical state, odor, color and melting point.

Melting point determination

Melting point of the Natamycin was determined by using capillary tube method. The small amount of the drug was filled in a 0.2 mm capillary tube (one end is sealed with the help of flame) up to a height of about 3-4 mm. The capillary tube was placed in capillary slots of the melting point instrument. The heating was started and the temperature range at which drug started melting and whole sample got melted was noted.

Chemical test

Small amount of drug sample was taken, on a glass slide and a drop of concentrated hydrochloric acid was added to it.

Table 1.

Physical test of natamycin

Table 2.

Physical test of different cyclodextrin

Small amount of drug sample was taken, on a glass slide and a drop of concentrated phosphoric acid was added to it.

Solubility determination

The solubility study of drug was performed in different organic solvent (e.g. Methanol, Glacial Acetic acid, Glycerol, Propylene Glycol, Dimethyl sulfoxide and water) as per IP 1996.

Results and Discussion

The results of various evaluation parameters were carried out and discussed here under:

Analysis of pure drug and excipients

Physical test

The result for the physical examination carried out as per the procedure given under Natamycin Cyclodextrin.

Conclusion

The Natamycin is soluble Glacial acetic acid, dimethyl sulphoxide, insoluble in water, polyethylene Glycol 400 and sparingly soluble in Methanol and ethanol. Based upon the observations for various physico-chemical as well as the in-vivo studies it may be concluded that Cyclodextrin complexes of Natamycin can lead to an aqueous formulation (Natamycin eye drop) having better trans corneal permeability and thus can be proved to have faster and better antifungal efficiency.