Preparation and Evaluation of Chitosan Microspheres

Mousumi Kar* and Dr P K Choudhury**

*&**Dept. of Pharmaceutical Sciences, MLSU, Udaipur
*Corresponding
author & email: mousumi_s@rediffmail.com

In the present study, an effort has been made to develop chitosan microspheres for a water-soluble antidiabetic drug. The microspheres were prepared by denaturation process to retard the drug release and to obtain maximum drug loading. The prepared microspheres were characterized by loading efficiency, % entrapment, optical microscopy, scanning electron microscopy and release characteristics. The morphology of the microspheres was well within permissible limits, with size in the range of 200 to 250m. The drug release was sustained for more than 8 hrs. The drug release followed higuchi kinetics, indicating diffusion controlled drug release.

Metformin hydrochloride is an antidiabetic drug used to treat NIDDM (Yuen et al. 1999) and is indicated as an adjunct to diet to lower blood glucose in cases where hyperglycemia cannot be controlled satisfactorily on diet alone. It has got a short half-life of about two hours. Chitosan is a high molecular weight cationic polysaccharide, comprising copolymers of Glucosamine and N-acetyl Glucosamine obtained by the deacetylation of Chitin (Mishra et al. 2003). Because of its low production costs, biodegradability, biocompatibility, nontoxic nature (Illum, 1998) and recent FDA approval, chitosan has found pronounced application in multiparticulate drug delivery (Dubey and Parikh 2004). Chitosan microspheres have been prepared by chemical denaturation process, ion induced coagulation and spray drying methods (El-Gibaly, 2002). The main objective of this study was to find out the effect of introduction of calcium ion into the system during the emulsification-denaturation process. An attempt was also made to encapsulate and retard drug release of very highly water-soluble drug like Metformin hydrochloride in chitosan matrix involving minimum amount of glutaraldehyde.

The drug Metformin hydrochloride was gifted by Bombay Tablets, Mumbai. Chitosan was obtained as a gift sample from Central institute of fisheries technology, Kochi, India. All other chemicals used were of analytical grade.

The microspheres were prepared by using 40 ml of 2.5% w/v chitosan-drug solution, to which 10% calcium chloride dihydrate was added and the solution was stirred continuously at 1000 rpm for 10 min. Glutaraldehyde (25% solution) was added drop -wise while stirring at same speed. Curing was allowed for 30 min. The microspheres were allowed to settle, then filtered and dried in air for 24 hrs. The dried microspheres were sieved and kept in desiccator until used.

The % drug entrapment for each batch was calculated and found to be between 70 to 85%. The drug content was determined by UV spectrophotometer at 233 nm using Systronics UV-Visible spectrophotometer. The selected batches based on their morphology and drug entrapment were subjected to in vitro release study.

SEM of the drug loaded chitosan microspheres was taken. The shape and surface features of microspheres observed by optical microscopy and SEM suggest that incorporation of calcium chloride affected the hardness and size of the microspheres. The microspheres were hard, free flowing and discrete and almost oval in shape (Fig 2). The color was dark brown. Clumping was seen in some cases, which could be easily separated by gentle agitation. The size of microspheres ranged from 200 to 350m. . The drug was sustained for more than 8 hrs. The drug loading characteristics shows that addition of calcium chloride has some effect in the loading of drug. This could be due to increase in the strength of the gel produced due to action of glutaraldehyde on calcium-loaded chitosan drug particles. But with increase in the concentration of calcium chloride, the drug loading and sustaining effect was decreased (Fig 1). This effect was seen due to increased solubility of the drug in water. With the increase in the concentration of calcium chloride, an excess amount was left behind, which started solubilising on coming in contact with the aqueous media leaving behind pores for the easy passage of the drug.

The strong gel matrix formed due to the dual action of calcium chloride and glutaraldehyde was sufficient enough to sustain the drug release for 8hrs.

This novel method of formulation of microspheres utilizing chemical denaturation process could be utilized as a non-time consuming and easy method for the entrapment of drugs for sustained action in the form of microspheres.

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Fig 1. Comparative Release Profile of Formulations with Variable Calcium  
Chloride Concentrations.

Fig 2.:Scanning electron photomicrograph of chitosan microspheres

About Mrs. Mousumi Kar

Mrs. Mousumi Kar completed M Pharm. in Pharmaceutics from College of Pharmaceutical
Sciences, (COPS), Manipal, Karnataka state on the topic ‘Floating drug
delivery system for an antipsychotic agent’. Currently she is working
as Lecturer, Department of Pharmaceutical Sciences, Mohan Lal Sukhadia University,
Udaipur. She is also working towards her PhD .