Optimization of Release Conditions of Alzheimer's Drug Donepezil Hydrochloride from Sodium Alginate/Sodium Carboxymethyl Cellulose Blend Microspheres

• Published in: Journal of macromolecular science. Physics Vol. 53; no. 5; pp. 902 - 917
• Main Authors: Bulut, Emine, Şanli, Oya
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Taylor & Francis 04-05-2014
• Subjects: Applied sciences; Biological and medical sciences; blends; Cellulose and derivatives; controlled release; donepezil hydrochloride; drug delivery systems; Exact sciences and technology; General pharmacology; Medical sciences; Natural polymers; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; polymeric microspheres; Starch and polysaccharides; water soluble polymers; Stoichiometry; drug delivery systems; Water oil emulsion; Crosslink density; Composition effect; Drug carrier; Property processing relationship; donepezil hydrochloride; Calcium ion; Donepezil; Microencapsulation; Manufacturing; Cellulose ether; Release; blends; Cellulose(carboxymethyl); Swelling; Control release polymer; Gelation; water soluble polymers; Alginates; Antialzheimer agent; Experimental study; In vitro; Polyelectrolyte; controlled release; Morphology; Oside polymer; Microgel; Kinetics; polymeric microspheres
• ISSN: 0022-2348; 1525-609X
• DOI: 10.1080/00222348.2013.874310

Microspheres of blends of sodium alginate (NaAlg) and sodium carboxymethyl cellulose (NaCMC) were prepared by a water-in-oil (w/o) emulsion crosslinking method and used for the release of donepezil hydrochloride (DP), which is an Alzheimer's drug. The microspheres were characterized with Fourier transform infrared spectroscopy (FTIR), differantial scanning calorimetry (DSC), and scanning electron microscopy (SEM). The microsphere characteristics, including DP entrapment efficiency, particle size, equilibrium swelling degree (ESD), and DP release kinetics, were determined. The effects of the preparation conditions, including the NaAlg/NaCMC (w/w) ratio, drug/polymer (w/w) ratio, cross-linker concentration and time of exposure to the cross-linker, on the release of DP were investigated for successive gastrointestinal tract pH values of 1.2, 6.8, and 7.4 at 37°C. The release of DP increased with the increase in NaAlg/NaCMC (w/w) ratio and drug/polymer (d/p) ratio, while it decreased with increasing extent of cross-linking. The optimum DP release was obtained as 99.13% for a NaAlg/NaCMC (w/w) ratio of 2/1, d/p ratio of 1/4, CaCl
2
concentration of 5% and crosslinking time of 30 min. It was also observed from release results that DP release from the microspheres through the external medium was higher at low pH (1.2) values than that at high pH (6.8 and 7.4) values. The DP release of the microspheres followed either Fickian transport below a value of n < 0.5 or anomalous transport (n = 0.5-1.0).