Aqueous preparation and evaluation of albumin-chitosan microspheres containing indomethacin

Controlled-release egg albumin-chitosan microspheres containing indomethacin as a model drug were successfully prepared by coacervation method. The proposed method can offer a simple method for microsphere preparation in an aqueous system with the elimination of the use of organic solvents that are usually needed in conventional techniques of microencapsulation. The interaction between negatively charged egg albumin molecules in phosphate buffer, pH 7.2, or sodium hydroxide solution and positively charged chitosan molecules dissolved in diluted acetic acid to form an insoluble precipitate was the principle for the formation of the microspheres. The effects of many process variables, such as amount of formaldehyde as a cross-linking agent, stirring time, final pH of encapsulation medium, initial drug loading, and albumin concentration or albumin-to-chitosan weight ratio, on the properties of the prepared microspheres were investigated. Incorporation efficiencies of the microspheres to the drug were high in most cases and ranged between 63.3 +/- 3.6% and 92.39 +/- 3.2%, while particle sizes were 435.2 +/- 12.6 up to 693.9 +/- 34.6 mum for the different tested batches. On the other hand, the values of angles of repose and compressibility indices were in the range of 23.5 +/- 0.4 to 32.0 +/- 0.7 degrees and 11.1 +/- 0.7% to 23.6 +/- 0.7% respectively, which indicate overall good free flowing nature of the microspheres of all batches. The maximum required amount of the cross-linking agent was determined to avoid excessive unnecessary chemicals. It was also noticed that excessive time of stirring and excessive initial drug loading are not recommended as it may lead to microspheres of low properties. The pH of the encapsulation media (pH 3.77 up to pH 4.91) significantly affected the properties of the microspheres. As the pH of the encapsulation media was increased, the incorporation efficiency, particle size, and flowability decreased, along with increase of drug release rate, which could be related to incomplete cross linking of the microspheres matrix. It was also observed that high concentration of albumin solution and accordingly the increase of albumin-to-chitosan weight ratio were accompanied with increases in incorporation efficiency and particle size with improved microsphere flowability and slow indomethacin release. Thus, the proposed microspheres showed the ability to control the release of indomethacin, and their properties were highly affected by many process variables that could be controlled to obtain an optimized system.