Effect of alginate composition and gelling cation on micro-bead swelling

PURPOSE: The purpose of this study was to determine the roles of alginate composition and gelling cations on bead swelling, which affects its durability. METHOD: Using a 2-channel droplet generator, microspheres were generated with 1.5% solutions of low viscosity high-mannuronic acid (LVM), medium viscosity high-mannuronic acid (MVM), low viscosity high-guluronic acid (LVG) and medium viscosity high-guluronic acid (MVG) alginate. They were gelled by cross-linking with 1.1% solution of either BaCl2 or CaCl2. The diameters of the micro-beads were measured and recorded on day 0. The micro-beads were subsequently washed and incubated in saline at 37 degrees C for 2 weeks with size assessment every 2 days. The data were normalized by calculation of the percentage change from control (day 0) for all groups of micro-beads. RESULTS: Diameters of all beads were between 550 and 700 microm on day 0. Viscosity had no effect on swelling of Ba++- and Ca++-alginate micro-beads. Ca++-alginate micro-beads were more prone to swelling than the corresponding Ba++-alginate beads. High G-Ba++ beads had only a modest increase in size over time, in contrast to the high M-Ba++. CONCLUSION: Alginate composition and the gelling cation have significant effects on bead swelling.     

Effect of alginate composition and gelling cation on microbead swelling

Purpose: The purpose of this study was to determine the roles of alginate composition and gelling cations on bead swelling, which affects its durability.

Method: Using a 2-channel droplet generator, microspheres were generated with 1.5% solutions of low viscosity high-mannuronic acid (LVM), medium viscosity high-mannuronic acid (MVM), low viscosity high-guluronic acid (LVG) and medium viscosity high-guluronic acid (MVG) alginate. They were gelled by cross-linking with 1.1% solution of either BaCl₂ or CaCl₂. The diameters of the microbeads were measured and recorded on day 0. The microbeads were subsequently washed and incubated in saline at 37°C for 2 weeks with size assessment every 2 days. The data were normalized by calculation of the percentage change from control (day 0) for all groups of microbeads.

Results: Diameters of all beads were between 550–700 microns on day 0. Viscosity had no effect on swelling of Ba⁺⁺- and Ca⁺⁺-alginate microbeads. Ca⁺⁺-alginate microbeads were more prone to swelling than the corresponding Ba⁺⁺-alginate beads. High G-Ba⁺⁺ beads had only a modest increase in size over time, in contrast to the high M-Ba⁺⁺.

Conclusion: Alginate composition and the gelling cation have significant effects on bead swelling.     

Effect of alginate composition and purity on alginate microspheres

BACKGROUND: Alginate is commonly used to microencapsulate islets in experiments with islet allografts and xenografts for the treatment of Type I diabetes. The purpose of the present study is to determine the effects of alginate composition and purity on the morphology and size of microspheres. METHODS: Microcapsules produced with the impure alginate types, medium-viscosity high-guluronic acid (IMVG), low-viscosity high-G (ILVG), low-viscosity high-mannuronic acid (ILVM) and medium-viscosity high-M (IMVM) were compared with one another and others generated with a highly purified LVM (HPLVM) alginate. Droplets of 1.5% alginate from an air-syringe pump were gelled in 1.1% CaCl2 solution. While leaving the alginate pressure and needle recess constant, the air-jacket pressure was varied between 9.5-10.5 PPSI to enhance stable microcapsule generation and different batches of microbeads were made from each alginate type. RESULTS: The sizes of the high-guluronic acid alginate microbeads were consistently bigger than those of the corresponding high-mannuronic acid alginate beads at all air-jacket settings. At the optimal air-jacket pressure of 9.0 PPSI, the mean+SD diameter of the IMVG microbeads was 780 + 20 microm, while that of IMVM was 607 + 44 microm (p < 0.0001, n=30). Similarly, the mean ILVG microbead diameter was 816+28 microm compared to 656+26 microm for ILVM capsules (p<0.0001, n=30). Less polymorphism was found with the HPLVM microspheres than with the ILVM microbeads. CONCLUSION: Highly purified high-mannuronic acid alginate will provide smaller, spherical microcapsules suitable for islet cell transplantation.     

Effect of alginate composition and purity on alginate microspheres

Background: Alginate is commonly used to microencapsulate islets in experiments with islet allografts and xenografts for the treatment of Type I diabetes. The purpose of the present study is to determine the effects of alginate composition and purity on the morphology and size of microspheres. Methods: Microcapsules produced with the impure alginate types, medium-viscosity high-guluronic acid (IMVG), low-viscosity high-G (ILVG), low-viscosity high-mannuronic acid (ILVM) and medium-viscosity high-M (IMVM) were compared with one another and others generated with a highly purified LVM (HPLVM) alginate. Droplets of 1.5% alginate from an air-syringe pump were gelled in 1.1% CaCl₂ solution. While leaving the alginate pressure and needle recess constant, the air-jacket pressure was varied between 9.5–10.5 PPSI to enhance stable microcapsule generation and different batches of microbeads were made from each alginate type. Results: The sizes of the high-guluronic acid alginate microbeads were consistently bigger than those of the corresponding high-mannuronic acid alginate beads at all air-jacket settings. At the optimal air-jacket pressure of 9.0 PPSI, the mean+SD diameter of the IMVG microbeads was 780+20?µm, while that of IMVM was 607+44?µm (p<0.0001, n?=?30). Similarly, the mean ILVG microbead diameter was 816+28 µm compared to 656+26?µm for ILVM capsules (p<0.0001, n?=?30). Less polymorphism was found with the HPLVM microspheres than with the ILVM microbeads. Conclusion: Highly purified high-mannuronic acid alginate will provide smaller, spherical microcapsules suitable for islet cell transplantation.     

Controlling the size of alginate gel beads by use of a high electrostatic potential

The effect of several parameters on the size of alginate beads produced by use of an electrostatic potential bead generator was examined. Parameters studied included needle diameter, electrostatic potential, alginate solution flow rate, gelling ion concentration and alginate concentration and viscosity, as well as alginate composition. Bead size was found to decrease with increasing electrostatic potential, but only down to a certain level. Minimum bead size was reached at between 2-4 kV/cm for the needles tested. The smallest alginate beads produced (using a needle with inner diameter 0.18 mm) had a mean diameter of approximately 300 microm. Bead size was also found to be dependent upon the flow rate of the fed alginate solution. Increasing the gelling ion concentration resulted in a moderate decrease in bead size. The concentration and viscosity of the alginate solution also had an effect on bead size as demonstrated by an increased bead diameter when the concentration or viscosity was increased. This effect was primarily an effect of the viscosity properties of the solution, which led to changes in the rate of droplet formation in the bead generator. Lowering the flow rate of the alginate solution could partly compensate for the increase in bead size with increased viscosity. For a constant droplet size, alginates with a low G block content (F(GG) approximately 0.20) resulted in approximately 30% smaller beads than alginates with a high G block content (F(GG) approximately 0.60). This is explained as a result of differences in the shrinking properties of the beads.     

Controlling the size of alginate gel beads by use of a high electrostatic potential

The effect of several parameters on the size of alginate beads produced by use of an electrostatic potential bead generator was examined. Parameters studied included needle diameter, electrostatic potential, alginate solution flow rate, gelling ion concentration and alginate concentration and viscosity, as well as alginate composition. Bead size was found to decrease with increasing electrostatic potential, but only down to a certain level. Minimum bead size was reached at between 2-4 kV/cm for the needles tested. The smallest alginate beads produced (using a needle with inner diameter 0.18 mm) had a mean diameter of ~300 #181;m. Bead size was also found to be dependent upon the flow rate of the fed alginate solution. Increasing the gelling ion concentration resulted in a moderate decrease in bead size. The concentration and viscosity of the alginate solution also had an effect on bead size as demonstrated by an increased bead diameter when the concentration or viscosity was increased. This effect was primarily an effect of the viscosity properties of the solution, which led to changes in the rate of droplet formation in the bead generator. Lowering the flow rate of the alginate solution could partly compensate for the increase in bead size with increased viscosity. For a constant droplet size, alginates with a low G block content (F GG #44 0.20) resulted in ~30% smaller beads than alginates with a high G block content (F GG #44 0.60). This is explained as a result of differences in the shrinking properties of the beads.     

海藻酸钙凝胶微丸作为口服缓释给药载体的研究

将海藻酸钠溶液滴入胶凝剂氯化钙溶液中制备了海藻酸钙凝胶微丸。以胶凝过程中凝胶微丸重量变化 (失水量 )研究了胶凝速率及不同浓度海藻酸钠溶液 ( 1 %～ 4 % )与氯化钙溶液 ( 0 0 5～0 2 0mol/L)对胶凝速率的影响 ,结果是 6h前胶凝速率快 ,随后减慢 ,约 70h胶凝完全 ,氯化钙溶液的浓度≥ 0 1mol/L对胶凝速率无明显影响。干燥的凝胶微丸在不同水性介质中溶胀试验结果表明 :在温度约 37℃时 ,微丸在蒸馏水和 0 1mol/L盐酸 ( pH1 0 )中几乎不溶胀 ,而在磷酸盐缓冲溶液( pH6 8)中1h溶胀 ,溶胀后的微丸直径是干燥前湿微丸直径的 1 80 %。海藻酸钙凝胶微丸这种溶胀的 pH敏感性 ,使它能成为口服药物缓释制剂的载体。以硝苯地平为模型药物制备的海藻酸钙凝胶微丸 ,其体外释放试验结果 ,2h累积释放量为 2 0 %～ 30 % ,6h为 6 0 %～ 80 % ,1 2h时大于85 %。药物从微丸中的释放是以扩散和骨架溶蚀相结合的方式。由此可见 ,硝苯地平的海藻酸钙凝胶微丸具有缓释作用     

Mechanisms of formation and disintegration of alginate beads obtained by prilling

In this paper, compendial sodium alginate beads have been manufactured by laminar jet break-up technology. The effect of polymer concentration, viscosity and polymeric solution flow rate on the characteristics of beads was studied. Size distribution of alginate beads in the hydrated state was strongly dependent on the flow rate and viscosity of polymer solutions, since a transition from laminar jet break-up conditions to vibration-assisted dripping was observed. The re-hydration kinetics of dried beads in simulated gastric fluid (SGF) showed that the maximum swelling of beads was reached after 1-2 h, with an increase in volume of two to three times and a time lag dependent on the polymer concentration. The re-hydration swelling profiles in simulated intestinal fluid (SIF) showed no time lag and higher swelling volume; moreover, in this medium after the maximum swelling was reached, the bead structure was quickly disaggregated because of the presence in the medium of phosphate able to capture calcium ions present in the alginate gel structure.     

Preparation andin vitro release of melatonin-loaded multivalent cationic alginate beads

The sustained release dosage form which delivers melatonin (MT) in a circadian fashion over 8 h is of clinical value for those who have disordered circadian rhythms because of its short half-life. The purpose of this study was to evaluate the gelling properties and release characteristics of alginate beads varying multivalent cationic species (Al⁺⁺⁺, Ba⁺⁺, Ca⁺⁺, Mg⁺⁺, Fe⁺⁺⁺, Zn⁺⁺). The surface morphologies of Ca- and Ba-alginate beads were also studied using scanning electron microscope (SEM). MT, an indole amide pineal hormone was used as a model drug. The Ca⁺⁺, Ba⁺⁺, Zn⁺⁺, Al⁺⁺⁺, and Fe⁺⁺⁺ ions except Mg⁺⁺ induced gelling of sodium alginate. The strength of multivalent cationic alginate beads was as follows: Al⁺⁺⁺?Fe⁺⁺⁺<Zn⁺⁺<Ca⁺⁺?Ba⁺⁺. In case of Al⁺⁺⁺, the induced hydrogel beads were very fragile and less spherical. Fe-alginate beads were also fragile but stronger compared to Al-alginate beads. Ba-alginate beads, had a similar gelling strength but was less spherical when compared to Ca-alginate beads. Zn-alginate beads were weaker than Ca- and Ba-alginate beads. Very crude and rough crystals of Ba- and Ca-alginate beads at higher magnifications were observed. However, the type and shape of rough crystals of Ba- and Ca-alginate beads were quite different. No significant differences in release profiles from MT-loaded multivalent cationic alginate beads were observed in the gastric fluid. Most drugs were continuously released upto 80% for 5 h, mainly governed by the passive diffusion without swelling and disintegrating the alginate beads. In the intestinal fluid, there was a significant difference in the release profiles of MT-loaded multivalent cationic alginate beads. The release rate of Ca-alginate beads was faster when compared to other multivalent cationic alginate beads and was completed for 3 h. Ba-alginate beads had a very long lag time (7 h) and then rapidly released thereafter. MT was continuously released from Fe-and Zn-alginate beads with initial burstout release. It is assumed that the different release profiles of multivalent cationic alginate beads resulted from forces of swelling and disintegration of alginate beads in addition to passive diffusion, depending on types of multivalent ions, gelling strength and drug solubility. It was estimated that 0.2 M CaCl₂ concentration was optimal in terms of trapping efficiency of MT and gelling strength of Ca-alginate beads. In the gastric fluid, Ca-alginate beads gelled at 0.2 M CaCl₂ concentration had higher bead strength, resulting in the most retarded release when compared to other concentrations. In the intestinal fluid, the decreased release of Ca-alginate beads prepared at 0.2 M CaCl₂ concentration was also observed. However, release profiles of Ca-alginate beads were quite similar regardless of CaCl₂ concentration. Either too low or high CaCl₂ concentrations may not be useful for gelling and curing of alginate beads. Optimal CaCl₂, concentrations must be decided in terms of trapping efficiency and release profiles of drug followed by curing time and gelling strength of alginate beads.     

Preparation and in vitro characterization of glibenclamide-loaded alginate hexyl-amide beads: a novel drug delivery system to improve the dissolution rate

Abstract

Objective: This investigation aimed to synthesize amphiphilic hexyl amidic derivative of alginate to be used in the preparation of glibenclamide-loaded release system of improved dissolution rate.

Materials and methods: Hexyl amine was associated to the activated carboxylic acid moieties of alginate to synthesize alginate hexyl amide polymer (AHAP). This polymer in comparison to alginate was used in different concentrations for preparing beads containing glibenclamide by an ionic gelation using Ca⁺⁺ as gelling ion. The prepared beads were characterized by DSC, FTIR and scanning electron microscope. The swelling behavior, drug loading capacity and release behavior were studied.

Results and discussion: The results showed that the prepared AHAP beads were smaller in size and more spherical. The surface was highly corrugated with much and wider pore size. The beads showed a high drug loading capacity and efficacy that was affected by the polymer concentration. The drug release rate from AHAP beads reached 100% after 4, 8 and 12 hours in comparison to 75.3%, 73.2% and 69.2% from alginate beads at 3%, 2% and 1% polymer concentrations, respectively.

Conclusion: It can thus be concluded that the amphiphilic AHAP-based bead is a simple and efficient delivery system of promising industrial significance for the improvement of the dissolution rate.     

Influence of viscosity and uronic acid composition of alginates on the properties of alginate films and microspheres produced by emulsification

This study investigated the influence of viscosity and uronic acid composition of alginates on the properties of alginate films and microspheres produced by emulsification. Tensile properties of films were determined while the yield, size, drug contents and release characteristics of the microspheres were examined. Tensile properties of calcium alginate matrix were significantly affected by the orientation and arrangement of the polymer chains. High viscosity alginates gave rise to higher yields and bigger microspheres. Generally, microspheres with high drug content and slower rate of drug release had high Ca2+ contents and were produced from alginates of higher viscosity. Within an alginate microsphere batch, small sized microsphere fractions had higher drug contents but showed faster drug release rates. Microspheres having a defined size range revealed great dependence of encapsulation efficiency and drug release rates on viscosity and extent of Ca2+-alginate interaction. Viscosity appeared to exert a predominant influence on the microsphere properties.     

Microencapsulation of a recombinant aminopeptidase (PepN) from Lactobacillus rhamnosus S93 in chitosan-coated alginate beads

A recombinant aminopeptidase (90 kDa) of Lactobacillus rhamnosus S93 produced by E. coli was encapsulated in alginate or chitosan-treated alginate beads prepared by an extrusion method. This study investigated the effects of alginate, CaCl2, chitosan concentrations, hardening time, pH and alginate/enzyme ratios on the encapsulation efficiency (EE) and the enzyme release (ER). Chitosan in the gelling solution significantly increased the EE from 30.2% (control) to 88.6% (coated). This polycationic polymer retarded the ER from beads during their dissolution in release buffer. An increase in alginate and chitosan concentrations led to greater EE and lesser ER from the beads. The greatest EE was observed in a pH 5.4 solution (chitosan-CaCl2) during bead formation. Increasing the CaCl2 concentration over 0.1 M neither affected the EE nor the ER. Increasing hardening time beyond 10 min led to a decrease in EE and the alginate:enzyme ratio (3 : 1) was optimal to prevent the ER.     

The Controlled Release of Prednisolone Using Alginate Gel

In a release study of alginate gel beads, swelling and erosion of the beads were observed at pH 6.8, whereas no swelling occurred at pH 1.2. The amount of released prednisolone (PL) was greater at pH 6.8 than at pH 1.2. The lower the ratio of mannuronic acid block to guluronic acid block in alginate, the slower the release of PL. An increase in loaded PL in the beads resulted in a slower release of PL. The decrease in bead size caused a rapid release of PL. The addition of sodium alginate propylene glycol ester elevated the extent of PL release. The plasma profile of PL showed sustained-release behavior after the oral administration of the beads to beagles. Furthermore, the correlation between in vitro release and in vivo absorption of PL for various alginate gel beads was evaluated using deconvolution and convolution methods. The in vivo absorption of PL was correlated with the PL release at pH 1.2, and it differed from that at pH 6.8. The release of PL from alginate gel beads in vivo appeared to occur under conditions that cause little swelling.     

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.     

Simultaneous determination of amiloride and furosemide in pharmaceutical formulations by first digital derivative spectrophotometry

Controlled release beads were prepared by using alginate (ALG), konjac glucomannan (KGM) and chitosan (CHI). Bovine serum albumin and insulin were used as model proteins for in vitro assessments. It was observed that KGM could be contained within beads, and faintness hydrogen binding and electrostatic interaction exist between ALG and KGM by infrared spectra. Clear dents were found on the surface of beads using KGM by scanning electron microscopy. Use of KGM could help increase the payload of drug. After beads were treated by 0.1 N HCl for 4 h and put into pH 7.4 buffers, protein was released from ALG-CHI beads within 1 h, while it was lost from ALG-KGM-CHI beads for 3 h. However, the leaking of protein from ALG-KGM-CHI beads was also increased in 0.1 N HCl solution. Concentration of gelling ion had great effect on release rate and gel structure. Studies of water of hydration had shown that swelling of ALG-KGM-CHI beads was higher than that of ALG-CHI beads in acidic solution, but the opposite result was obtained in alkali solution. The result indicated that the diffusion of protein was related to the viscosity and swelling properties of KGM.     

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.     

Calcium alginate microparticles for oral administration: I: effect of sodium alginate type on drug release and drug entrapment efficiency

The natural polymers alginate and chitosan were used for the preparation of controlled release nicardipine HCl gel microparticles. The effect of the mannuronic/guluronic acid content and the alginate viscosity on the prolonged action of the microparticles, which were prepared with different types of alginates, were investigated. The mean particle sizes and the swelling ratios of the microparticles were also determined. The in vitro release studies were carried out with a flow-through cell apparatus in different media (pH 1.2, 2.5, 4.5, 7 and 7.5 buffer solutions). The release of nicardipine was extended with the alginate gel microparticles prepared with guluronic acid rich alginate. After the determination of the most appropriate alginate type, the effect of alginatechitosan complex formation was studied on the release pattern of drug incorporated. It was observed that the alginate-chitosan complex formation reduced the erosion of the alginate-chitosan matrix at pH 7-7.5. The release of drug from the chitosan-alginate gel microparticles took place by both diffusion through the swollen matrix and relaxation of the polymer at pH 1.2-4.5     

Recent advances and perspectives on coated alginate microspheres for modified drug delivery

BACKGROUND: Alginate microspheres represent a useful tool for modified drug delivery. Their preparation is quite easy and is usually based on the gelling properties of the polysaccharide in the presence of divalent ions; nevertheless, microparticles prepared only with calcium alginate show several problems, mainly related to the mechanical stability and to the release that, in most cases, is too fast. To overcome such inconveniences, polymer-coated alginate microspheres and/or appropriately interpenetrating polymer network (semi-IPNs and IPNs) structures formed with alginate and other macromolecules were developed. OBJECTIVE: This article reports a synthetic overview on the most recent searches carried out on coated alginate microspheres. METHODS: After a section focused on the microsphere preparation, this article is divided into several main topics related to the specific polymer that was used as a coating material to provide a rationale in reporting literature data. In the last section, the advantages and disadvantages of the various approaches are discussed and the authors' opinion on perspectives for further studies and novel applications of coated alginate microspheres are reported. CONCLUSION: Ca(2+)-alginate microparticles could experience a new era if scientists will increase their efforts in developing microparticles with smart properties.     

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.     

Gastric resistant microbeads of metal ion cross-linked carboxymethyl guar gum for oral drug delivery

Ionic cross-linking of sodium carboxymethyl guar gum as a mild method for microencapsulation of sensitive drugs, like proteins, is presented. When a solution of sodium salt of carboxymethyl guar gum, containing BSA as a model drug, is added, as droplets, to different multivalent metal ion solutions, they get cross-linked to form insoluble microbeads. The amount of protein retained, morphology of the resulting beads and the subsequent release of the retained protein is simulated intestinal fluids varied with the type of metal ion as well as it's concentration. Trivalent metal ions like Al +++ and Fe +++ were found to be superior to divalent metal ions like Ba ++, Ca ++, Cu ++ and Cd ++ . The optimum concentration around which these ions provide maximum drug retention was found to be much lower for trivalent ions. Beads cross-linked with them released the protein over a longer duration in enzyme free simulated intestinal fluid, than those cross-linked with divalent ions. Mg ++, Sr ++, Co ++ and Zn ++ failed to form isolable beads.