A comparative histological study of alginate beads as a promising controlled release delivery for mefenamic acid

The new mefenamic acid-alginate bead formulation prepared by ionotropic gelation method using 3 x 2(2) factorial design has shown adequate controlled release properties in vitro. In the present study, the irritation effects of mefenamic acid (MA), a prominent non-steroidal anti-inflammatory (NSAI) drug, were evaluated on rat gastric and duodenal mucosa when suspended in 0.5% (w/v) sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads. Wistar albino rats weighing 200 +/- 50 g were used during in vivo animal studies. In this work, biodegradable controlled release MA beads and free MA were evaluated according to the degree of gastric or duodenal damage following oral administration in rats. The gastric and duodenal mucosa was examined for any haemorrhagic changes. Formulation code A10 showing both Case II transport and zero order drug release and t(50) % value of 5.22 h was chosen for in vivo animal studies. For in vivo trials, free MA (100 mgkg(-1)), blank and MA (100 mgkg(-1)) loaded alginate beads (formulation code A10) were suspended in 0.5% (w/v) NaCMC solution and each group was given to six rats orally by gavage. NaCMC solution was used as a control in experimental studies. In vivo data showed that the administration of MA in alginate beads prevented the gastric lesions.     

A Comparative Histological Study of Alginate Beads as a Promising Controlled Release Delivery for Mefenamic Acid

The new mefenamic acid-alginate bead formulation prepared by ionotropic gelation method using 3 × 2² factorial design has shown adequate controlled release properties in vitro. In the present study, the irritation effects of mefenamic acid (MA), a prominent non-steroidal anti-inflammatory (NSAI) drug, were evaluated on rat gastric and duodenal mucosa when suspended in 0.5% (w/v) sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads. Wistar albino rats weighing 200 ± 50 g were used during in vivo animal studies. In this work, biodegradable controlled release MA beads and free MA were evaluated according to the degree of gastric or duodenal damage following oral administration in rats. The gastric and duodenal mucosa was examined for any haemorrhagic changes. Formulation code A10 showing both Case II transport and zero order drug release and t₅₀ % value of 5.22 h was chosen for in vivo animal studies. For in vivo trials, free MA (100 mgkg^?1), blank and MA (100 mgkg^?1) loaded alginate beads (formulation code A10) were suspended in 0.5% (w/v) NaCMC solution and each group was given to six rats orally by gavage. NaCMC solution was used as a control in experimental studies. In vivo data showed that the administration of MA in alginate beads prevented the gastric lesions.     

Biphasic release characteristics of dual drug-loaded alginate beads

The dual drug-loaded alginate beads simultaneously containing drug in inner and outer layers were prepared by dropping plain (single-layered) alginate beads into CaCl₂ solution. The release characteristics were evaluated in simulated gastric fluid for 2 h followed by intestinal fluids thereafter for 12 h. The surface morphology and cross section of dual drug-loaded alginate beads was also investigated using scanning electron microscope (SEM). The poorly water-soluble ibuprofen was chosen as a model drug. The surface of single-layered and dual drug-loaded alginate beads showed very crude and roughness, showing aggregated particles, surface cracks and rough crystals. The thickness of dual drug-loaded alginate beads surrounded by outer layer was ranged from about 57 to 329μm. The distinct chasm between inner and outer layers was also observed. In case of single-layered alginate beads, the drug was not released in gastric fluid but was largely released in intestinal fluid. However, the release rate decreased as the reinforcing Eudragit^® polymer contents increased. When the plasticizers were added into polymer, the release rate largely decreased. The release rate of dual drug-loaded alginate beads was stable in gastric fluid for 2 h but largely increased when switched in intestinal fluid. The drug linearly released for 4 h followed by another linear release thereafter, showing a distinct biphasic release characteristics. There was a difference in the release profiles between single-layered and dual drug-loaded alginate beads due to their structural shape. However, this biphasic release profiles were modified by varying formulation compositions of inner and outer layer of alginate beads. The release rate of dual drug-loaded alginate beads slightly decreased when the outer layer was reinforced with Eudragit^® RS100 polymers. In case of dual drug-loaded alginate beads with polymer-reinforced outer layer only, the initial amount of drug released was low but the initial release rate (slope) was higher due to more swellable inner cores when compared to polymer-reinforced inner cores. The current dual drug-loaded alginate beads may be used to deliver the drugs in a time dependent manner.     

Sulindac loaded alginate beads for a mucoprotective and controlled drug release

Ionotropic gelation was used to entrap sulindac into calcium alginate beads as a potential drug carrier for the oral delivery of this anti-inflammatory drug. Beads were investigated in vitro for a possible sustained drug release and their use in vivo as a gastroprotective system for sulindac. Process parameters such as the polymer concentration, polymer/drug ratio, and different needle diameter were analysed for their influences on the bead properties. Size augmented with increasing needle diameter (0.9 mm needle: 1.28 to 1.44 mm; 0.45 mm needle: 1.04 to 1.07 mm) due to changes in droplet size as well as droplet viscosity. Yields varied between 87% and 98% while sulindac encapsulation efficiencies of about 88% and 94% were slightly increasing with higher alginate concentrations. Drug release profiles exhibited a complete release for all formulations within 4 hours with a faster release for smaller beads. Sulindac loaded alginate beads led to a significant reduction of macroscopic histological damage in the stomach and duodenum in mice. Similarly, microscopic analyses of the mucosal damage demonstrated a significant mucoprotective effect of all bead formulation compared to the free drug. The present alginate formulations exhibit promising properties of a controlled release form for sulindac; meanwhile they provide a distinct tissue protection in the stomach and duodenum.     

Multi-unit floating alginate system: effect of additives on ciprofloxacin release

In an attempt to fabricate floating beads of ciprofloxacin, drugloaded alginate beads were prepared by simultaneous external and internal gelation. The effect of blending of alginate with gellan, hydroxypropyl methylcellulose, starch, and chitosan on the bead properties were evaluated. Beads were spherical with incorporation efficiency in the range of 52.81 +/- 2.64 to 78.95 +/- 1.92%. Beads exhibited buoyancy over a period of 7-24 hr based on the formulation variables. In vitro release of ciprofloxacin from the alginate beads in simulated gastric fluid (SGF) (0.1 N HCl, pH 1.2), was influenced significantly (p < 0.001) by the properties and concentration of additives. Among the polymers incorporated into alginate beads. Hydroxy propyl methylcellulose (HPMC) provided an extended release over 7 hr. The drug release predominately followed Higuchi's square root model.     

载葛根素的海藻酸镁胃内滞留释药系统的研究

采用滴制法制备微丸\选取海藻酸钠为载体材料,氯化镁为交联剂,碳酸氢钠为制泡剂,海藻酸钠与镁离子发生交联反应制得胃漂浮微丸,考察微丸的外观、粒径、微观结构、漂浮性以及释药行为.为延长药物在胃靶向释放时长,在单因素实验的基础上,以Eudragit L100和Eudragit RSALO作为载体材料制备载药固体分散体,粉碎过...     

An anti-inflammatory drug (mefenamic acid) incorporated in biodegradable alginate beads: development and optimization of the process using factorial design

The objective of this study was to prepare and evaluate biodegradable alginate beads as a controlled-release system for a water-insoluble drug, mefenamic acid (MA), using 3 x 2(2) factorial design by ionotropic gelation method. Therefore, the mefenamic acid dispersion in a solution of alginate was dropped into the cross-linking CaCl(2) solution and a fairly high yield (71-89%) of MA-alginate beads were obtained. Their encapsulation efficiencies were in the range of 79.3-98.99%. The effect of drug:polymer ratio, CaCl(2) concentration, and curing time on the time for 50% of the drug to be released (t(50%)), and the drug entrapment efficiency were evaluated with factorial design method. It was found that drug:polymer ratio and interaction of drug:polymer ratio and curing time had an important effect on the drug to be released (t(50%)). The effect of CaCl(2) concentration is also important on the drug release. On the other hand, all factors except CaCl(2) concentration were effective on the drug entrapment efficiency. The swelling properties of beads were also studied. The release mechanism was described and found to be non-Fickian, Case II, and Super Case II transport for the formulations. This study suggested a new mefenamic acid alginate bead formulation for oral delivery of nonsteroidal anti-inflammatory drugs, which cause gastric irritation.     

Development and evaluation of polyethyleneimine-treated calcium alginate beads for sustained release of diltiazem

The objective of this investigation is to develop a multi-unit sustained release dosage form of a water soluble drug from a completely aqueous environment avoiding the use of any organic solvent. The drug was complexed with resin and calcium alginate or polyethyleneimine-treated calcium alginate beads loaded with the resinate were prepared by a ionic/polyelectrolyte complexation method. The effect of different formulation variables on the characteristics of the beads was investigated. Although the drug release from spherical and smooth-surfaced calcium alginate beads in both acidic and alkaline dissolution media were slower than those obtained from plain resinate, none of the variables were found to prolong the drug release considerably due to rapid swelling and disintegration of calcium alginate beads in alkaline medium. On the other hand, drug release from polyethyleneimine-treated calcium alginate beads in acidic medium did not increase appreciably following a burst release. However, in alkaline medium, the drug release was found to increase gradually and extend over a different period of time depending on the intensity of polyethyleneimine treatment. Scanning electron micrographs revealed the formation of a dense membrane around the resinate-loaded calcium alginate matrix. The membrane appeared to be responsible for reduced swelling and protracted disintegration of the beads resulting in slow release of the drug. The results indicate that sustained release of a water soluble drug from polyethyleneimine-treated calcium alginate beads could be achieved by adjusting the formulation variables.     

Development and evaluation of polyethyleneimine-treated calcium alginate beads for sustained release of diltiazem

The objective of this investigation is to develop a multi-unit sustained release dosage form of a water soluble drug from a completely aqueous environment avoiding the use of any organic solvent. The drug was complexed with resin and calcium alginate or polyethyleneimine-treated calcium alginate beads loaded with the resinate were prepared by a ionic/polyelectrolyte complexation method. The effect of different formulation variables on the characteristics of the beads was investigated. Although the drug release from spherical and smooth-surfaced calcium alginate beads in both acidic and alkaline dissolution media were slower than those obtained from plain resinate, none of the variables were found to prolong the drug release considerably due to rapid swelling and disintegration of calcium alginate beads in alkaline medium. On the other hand, drug release from polyethyleneimine-treated calcium alginate beads in acidic medium did not increase appreciably following a burst release. However, in alkaline medium, the drug release was found to increase gradually and extend over a different period of time depending on the intensity of polyethyleneimine treatment. Scanning electron micrographs revealed the formation of a dense membrane around the resinate-loaded calcium alginate matrix. The membrane appeared to be responsible for reduced swelling and protracted disintegration of the beads resulting in slow release of the drug. The results indicate that sustained release of a water soluble drug from polyethyleneimine-treated calcium alginate beads could be achieved by adjusting the formulation variables.     

Potential of calcium pectinate beads for target specific drug release to colon

A pectin-based colon specific delivery system bearing 5-fluorouracil (5-FU) was developed for effective delivery of drug to the colon. Calcium pectinate gel (CPG) beads were prepared by ionotropic gelation method followed by enteric coating with Eudragit S-100. The CPG beads formed were spherical with smooth surfaces. CPG beads size was found to be in the range of 1.32+/-0 . 12-1.88+/-0.08 mm. The in vitro drug release was investigated using USP dissolution rate test paddle type apparatus in different simulated mediums. Release in PBS (pH 7.4) and simulated gastric fluid showed almost similar pattern and rate, whereas a significant increase in percent cumulative drug release (58.3+/-1.36%) was observed in medium containing rat caecal content, i.e. the amount of the drug released from the formulation was found to be 49.2+/-2.29 and 58.3+/-1.36% of drug with 2 and 4% w/v caecal matter after 24 h whereas in control study 33.2+/-1.19% of drug was released. Moreover, to induce the enzymes that specifically act on pectin, the rats were treated with 1 ml of 1% w/v dispersion of pectin for 2 and 4 days and release rate studies were repeated in SCF in the presence of 2 and 4% w/v of caecal matter. A marked improvement in the drug release was observed in presence of caecal matter obtained after induction when compared to those without induction. The percentage of drug released after 24 h release was observed to be 69.3+/-2.81 and 86.7+/-3.15%, respectively, with 2 and 4% w/v rat caecal matter obtained after 2 days of enzyme induction, and 82.4+/-3.15 and 98.7+/-4.26%, respectively, after 4 days of enzyme induction. In vivo data showed that Eudragit S-100 coated calcium pectinate beads delivered most of its drug load (93.2+/-3.67%) to the colon after 9 h, which reflects its targeting potential to the colon. It is concluded that orally-administered 5-FU loaded Eudragit S-100 coated calcium pectinate beads can be used effectively for the specific delivery of drug to the colon.     

Preparation and release characteristics of polymer-reinforced and coated alginate beads

Polymeric reinforcement and coatings of alginate beads were carried out to control the release rate of drug from alginate beads. A poorly water-soluble ibuprofen (IPF) was selected as a model drug. A commercially available Eudragit^® RS100 was also used as a polymer. Effects of polymeric contents, the presence of plasticizers and amount of drug loading on the release rate of drug were investigated. The release rate of drug from alginate beads in the simulated gastric fluid did not occur within 2 h but released immediately when dissolution media were switched to the simulated intestinal fluid. No significant difference of release rate from polymer-reinforced alginate bead without plasticizers was observed when compared to plain (simple) beads. However, the release rate of drug from polymer-reinforced alginate beads was further sustained and retarded when aluminium tristearate (AT) as a plasticizer was added to polymer. However, polyethylene glycol 400 (PEG400) did not change the release rate of drug from alginate beads although PEG400 was used to improve dispersion of polymer and sodium alginate, and plasticize Eudragit^® RS100 polymer. The presence of plasticizer was crucial to reinforce alginate gel matrices using a polymer. As the amount of drug loading increased, the release rate of drug increased as a result of decreasing effects of polymer contents in matrices. The significantly sustained release of drug from polymer-coated alginate beads occurred as the amount of polymer increased because the thickness of coated membrane increased so that cracks and pores of the outer surface of alginate beads could be reduced. The sustained and retarded action of polymer-reinforced and coated beads may result from the disturbance of swelling and erosion (disintegration) of alginate beads. From these findings, polymeric-rein-forcement and coatings of alginate gel beads can provide an advanced delivery system by retarding the release rate of various drugs.     

5-Fluorouracil encapsulated alginate beads for the treatment of breast cancer

Alginate beads containing 5-fluorouracil (5-FU) were prepared by the gelation of alginate with calcium cations. Alginate beads loaded with 5-FU were prepared at 1.0 and 2.0% (w/v) polymers. The effect of polymer concentration and the drug loading (1.0, 5.0 and 10%) on the release profile of 5-FU was investigated. As the drug load increased, larger beads were obtained in which the resultant beads contained higher 5-FU content. The encapsulation efficiencies obtained for 5-FU loads of 1.0, 5.0 and 10% (w/v) were 3.5, 7.4 and 10%, respectively. Scanning electron microscopy (SEM) and particle size analysis revealed differences between the formulations as to their appearance and size distribution. The amount of 5-FU released from the alginate beads increased with decreasing alginate concentrations.     

Amoxycillin release from a floating dosage form based on alginates

Floating alginate beads have been prepared from alginate solutions containing either dissolved or suspended amoxycillin. The beads were produced by the dropwise addition of the alginate into calcium chloride solution, followed by removal of the gel beads and freeze drying. Drug release studies showed that beads prepared with the drug in solution provided some sustained release characteristics and that these could be improved by the addition of amylose. In all cases, the drug release was consistent with release of a dissolved solute from a granular or porous matrix. The beads retained their buoyancy when amylose and amoxycillin were incorporated, exhibiting resultant weight values greater than zero after 20 h. Preparation of the beads from alginate solutions containing the drug in suspension allowed higher drug loadings, at the expense of faster release and lower buoyancy.     

Preparation of dual crosslinked alginate-chitosan blend gel beads and in vitro controlled release in oral site-specific drug delivery system

Alginate-chitosan (ALG-CS) blend gel beads were prepared based on Ca2+ or dual crosslinking with various proportions of alginate and chitosan. The homogeneous solution of alginate and chitosan was dripped into the solution of calcium chloride; the resultant Ca2+ single crosslinked beads were dipped in the solution of sodium sulfate sequentially to prepare dual crosslinked beads. The dual crosslinkage effectively promoted the stability of beads under gastrointestinal tract conditions. The sustained release profiles of single and dual crosslinked gel beads loaded bovine serum albumin (BSA), a model protein drug, were investigated in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and simulated colonic fluid (SCF). In SGF, compared to Ca2+ single crosslinked beads, from which BSA released fast and the cumulative drug release percentages were about 80% of all formations in 4 h, the BSA total release from dual crosslinked gel beads was no more than 3% in 8 h. In SIF and SCF, Ca2+ single crosslinked beads were disrupted soon associating with the fast drug release. As to the dual crosslinked beads, the BSA total release from the ALG-CS mass ratio 9:1 (81.24%) was higher than that of 7:3 and 5:5 (less than 60%) in 8 h in SIF; the BSA release from all beads was much faster in SCF than in SIF. The dual crosslinked beads incubated in gastrointestinal tract conditions, the BSA cumulative release of ALG-CS mass ratios 9:1, 7:3 and 5:5 were respectively 2.35, 1.96, 1.76% (in SGF 4 h), 82.86, 78.83, 52.91% (in SIF 3 h) and 97.84, 96.81, 87.26% (in SCF 3 h), which suggested that the dual crosslinked beads have potential small intestine or colon site-specific drug delivery property.     

Comparison of the pharmaceutical properties of sustained-release gel beads prepared by alginate having different molecular size with commercial sustained-release tablet

Spherical alginate gel beads containing pindolol were prepared using three types of sodium alginate with different molecular size. The rate of gelation of sodium alginate in calcium chloride solution was in the range of 1.0 to 1.3 h-1 among the used three alginates, but the amount of water squeezed from the alginate gel beads during gelation increased from 5 to 40% with increasing molecular size of the alginate. The beads prepared were similar in diameter (1.2 mm after drying), weight (0.9 mg/bead), calcium content (27-29 micrograms/bead) and pindolol content (40-45%). Pindolol was rapidly released from all the alginate gel beads at pH 1.2 owing to the high solubility of pindolol, in spite of non-swelling of beads. On the other hand, pindolol release from alginate gel beads at pH 6.8 was dependent on the swelling of the beads and was significantly depressed compared to drug powder. Interestingly, the release rate of pindolol and the swelling rate of beads were markedly slow for gel beads prepared by low molecular size alginate. However, when the alginate gel beads were administered orally to beagle dogs, the serum levels of pindolol showed sustained-release profiles, depending on the molecular size of the alginate. The in vivo absorption of pindolol from alginate gel beads did not reflect their in vitro release profiles, because of a physical strength of beads in the intestinal tract. Furthermore, the in vivo and in vitro release of pindolol from alginate gel beads were compared with a commercial sustained-release tablet, Carvisken showed a rapid release of 50% of content in pH 1.2 fluid and residual 50% of pindolol were easily dissolved at pH 6.8. Although the release characteristics of pindolol from Carvisken and the alginate gel beads were completely different, the serum levels of pindolol in human volunteers were comparable.     

Sustained release of hydrophobic and hydrophilic drugs from a floating dosage form

Floating dosage forms enable the sustained delivery of drugs in the gastro-intestinal tract. In this study, a type of multi-unit floating gel bead was synthesized with calcium alginate, sunflower oil, and a drug of interest through an emulsification/gelation process. The alginate beads with oil addition were able to continuously float over the medium for 24h under constant agitation while the non-oily beads could not. Three kinds of drugs with different hydrophilicities, ibuprofen, niacinamide and metoclopramide HCl, were tested in the study. The hydrophobic drug ibuprofen was released in a sustained manner for 24h, due to the oil partitioning. With suitable modification, the beads were able to also release the hydrophilic drugs, niacinamide and metoclopramide HCl, for a similar duration. Therefore a floating dosage form that is able to sustain release both hydrophobic and hydrophilic drugs within its extended gastric retention time has been developed.     

Controlling release of metformin HCl through incorporation into stomach specific floating alginate beads

The aim of present study was to develop stomach specific floating beads of metformin hydrochloride for effective management of type 2 diabetes mellitus. The beads were evaluated for surface morphology, particle size, tapped density, true density, percent porosity, drug entrapment efficiency, percent yield, differential scanning calorimetry, in vitro floating ability and in vitro drug release. Stability studies were performed at 25 and 40 °C up to 45 days. Effectiveness of the formulations was evaluated in vivo by hypoglycemic response in both normal and diabetic albino rats. The beads were grossly spherical in shape, and average particle diameter of beads was found to be in the size range of 861.34 to 991.75 μm. Percent entrapment was found to be in the range of 77.61 to 82.48%. Beads demonstrated favorable in vitro floating ability. All the formulations followed a non-Fickian release mechanism. It was found that there was no significant effect on floating ability of aged beads since it floated up to an 8 h study period. In vivo studies on diabetic rats showed that the hypoglycemic effect induced by the metformin hydrochloride loaded alginate beads was significantly greater (P < 0.05) and more prolonged than that induced by the nonfloating beads. The results clearly demonstrated the ability of the formulation to maintain blood glucose level and improved the patient compliance by enhancing, controlling and prolonging the systemic absorption of metformin hydrochloride.     

Adipic acid dihydrazide treated partially oxidized alginate beads for sustained oral delivery of flurbiprofen

In this study, periodate oxidation of sodium alginate was controlled such that the oxidized alginate could form isolatable beads with Ca⁺² ions. The beads of oxidized alginate having a degree of oxidation 1 mol%, entrapped 89% flurbiprofen and released almost all of its content within 1.5 h in pH 7.2 phosphate buffer solution. The beads were covalently crosslinked with adipic dihydrazide (ADH) in addition to ionic crosslinks and were characterized. Scanning electron microscopy revealed that the beads were spherical having smooth surfaces. The drug entrapment efficiency decreased (90–86%) with increasing concentration of ADH (2–6% w/v) in the gelation medium. However, the beads prolonged the drug release in alkaline dissolution medium up to 8 h depending upon the concentration of ADH. The beads prepared with 2% ADH swelled more rapidly and led to faster drug release in either pH 1.2 HCl solution or pH 7.2 phosphate buffer solution. The swelling tendencies were reduced and the drug release became slower with higher concentrations in either fluid. The drug diffusion from the beads followed super case II transport mechanism. FTIR spectroscopy indicated stable nature of flurbiprofen in the beads and therefore had potential as sustained oral delivery system for the drug.     

An Anti-Inflammatory Drug (Mefenamic Acid) Incorporated in Biodegradable Alginate Beads: Development and Optimization of the Process Using Factorial Design

The objective of this study was to prepare and evaluate biodegradable alginate beads as a controlled-release system for a water-insoluble drug, mefenamic acid (MA), using 3 × 2² factorial design by ionotropic gelation method. Therefore, the mefenamic acid dispersion in a solution of alginate was dropped into the cross-linking CaCl₂ solution and a fairly high yield (71–89%) of MA-alginate beads were obtained. Their encapsulation efficiencies were in the range of 79.3–98.99%. The effect of drug:polymer ratio, CaCl₂ concentration, and curing time on the time for 50% of the drug to be released (t_50%), and the drug entrapment efficiency were evaluated with factorial design method. It was found that drug:polymer ratio and interaction of drug:polymer ratio and curing time had an important effect on the drug to be released (t_50%). The effect of CaCl₂ concentration is also important on the drug release. On the other hand, all factors except CaCl₂ concentration were effective on the drug entrapment efficiency. The swelling properties of beads were also studied. The release mechanism was described and found to be non-Fickian, Case II, and Super Case II transport for the formulations. This study suggested a new mefenamic acid alginate bead formulation for oral delivery of nonsteroidal anti-inflammatory drugs, which cause gastric irritation.     

The release behavior of brilliant blue from calcium-alginate gel beads coated by chitosan: the preparation method effect.

The aim of this study is to reveal how the release behavior of a model drug (brilliant blue, BB) from chitosan coating calcium-alginate gel beads (CCAGB) was influenced by the preparation methods. The CCAGB were prepared by dropping alginate solution into CaCl(2)/chitosan solution (method 1(a)), or into chitosan solution then gelled by CaCl(2) (method 1(b)), or into CaCl(2) solution then coated by chitosan (method 2). Scanning electron microscopy was used for morphology observation, and elemental analysis was applied to determine the chitosan content bound on calcium-alginate gel beads (CAGB). Compared to CAGB, the dried CCAGB had poorer shape and rougher surface morphology especially in methods 1(a) and (b); moreover, CCAGB was found to be more instable in 0.9% NaCl and serious burst of beads occurred when high concentration of alginate (3.0 and 5.0% w/v) was used. The influence on BB release from the beads by chitosan coating was not only related to the chitosan density on bead surface, but also preparation method and other factors. Under un-dried bead state in method 1(a), the increase of chitosan content prolonged BB release in 0.9% (w/v) NaCl; while in method 2, the increase of chitosan concentration over 0.1% (w/v) (3.0% (w/v) alginate concentration was used) resulted in more serious burst of beads and hence facilitated BB release. Furthermore, in both methods 1(a) and 2, the increase of alginate from 1.5 to 3.0 or 5.0% (w/v) usually resulted in the significant burst of beads and accelerated BB release when 0.3 or 0.5% (w/v) chitosan was used for coating. Drying process greatly influenced BB release profile due to the destroying of alginate-chitosan film. The acceleration of BB release from CCAGB by drying process was more significant in the case of method 1 than of method 2.