Preparation and Evaluation Of Drug-Containing Chitosan Beads

Abstract

Sulfadiazine beads were prepared by dropping drug-containing solutions of the positively charged polysaccharide, chitosan, into tripolyphosphate (TPP) solutions. The droplets instantaneously formed gelled spheres by ionotropic gelation, entrapping the drug within a three-dimensional network of the ionically linked polymer. To achieve maximum drug content, high payloads, short gelation times, low TPP concentrations, and a low internal to external phase ratio were required. The chitosan beads showed pH-dependent swelling and dissolution behavior. The beads swelled and dissolved in 0.1N HCl, while they stayed intact in simulated intestinal fluid. The release of sulfadiazine in 0.1N HCl decreased with increasing concentration of TPP, but was independent of the TPP concentration in intestinal fluids. The morphology of the beads was investigated by scanning electron microscopy. The porosity of the beads depended on the method of drying.     

pH-insensitive fabrication of gold nanoparticles with high concentration by ultrasound-assisted electrochemical process via aid of chitosan

In this work, we report a new pathway to prepare pure gold nanoparticles with high concentrations in acid solutions via the aid of chitosan without the addition of other stabilizers and reductants based on electrochemical methods. Interestingly, this fabrication of gold nanoparticles with high concentrations in solutions is pH-insensitive. The characteristics of prepared gold nanoparticles were examined by transmission electron microscopy (TEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (HRXPS) measurements. Experimental results indicate the concentration and the particle size of Au nanoparticles prepared in 0.1N HCl are ca. 50 ppm and 12 nm in diameter, respectively. Similar experiment performed in 0.1N NaCl with the aid of chitosan shows that the corresponding concentration of prepared Au nanoparticles is ca. 100 ppm. Further similar experiments performed in 0.1N HCl and 0.1N NaCl without the aid of chitosan show that the corresponding concentrations of prepared Au nanoparticles are ca. 1 and 60 ppm, respectively.     

Study of Formulation Variables on Properties of Drug-Gellan Beads by Factorial Design

ABSTRACT

The aim of the present study was to obtain cross-linked calcium-gellan beads containing diclofenac sodium as model drug, using full 3³ factorial design. Drug quantity, pH of cross-linking solution, and speed of agitation were selected as variables for factorial design. The resultant beads were evaluated by scanning electron microscopy (SEM), percent yield, entrapment efficiency, micromeritic properties, swelling and drug release studies. The drug-loaded beads were spherical with size range of 0.85–1.8 mm. Percent yield and entrapment efficiency of various batches were in the range of 86.48–98.28% w/w and 72.52–92.74% w/w, respectively. Calcium-gellan beads containing diclofenac sodium showed pH-dependent swelling and drug release properties. Swelling and drug release were significantly higher in pH 7.4 phosphate buffer than 0.1N HCl. The swelling ratio for beads was up to 22 and 3 for phosphate buffer and 0.1N HCl, respectively. Cumulative diclofenac sodium release from calcium-gellan beads was 12–35% in 0.1N HCl within 2 h, whereas complete drug release was observed within 3–4 h in pH 7.4 phosphate buffer.     

Study of formulation variables on properties of drug-gellan beads by factorial design

The aim of the present study was to obtain cross-linked calcium-gellan beads containing diclofenac sodium as model drug, using full 3(3) factorial design. Drug quantity, pH of cross-linking solution, and speed of agitation were selected as variables for factorial design. The resultant beads were evaluated by scanning electron microscopy (SEM), percent yield, entrapment efficiency, micromeritic properties, swelling and drug release studies. The drug-loaded beads were spherical with size range of 0.85-1.8 mm. Percent yield and entrapment efficiency of various batches were in the range of 86.48-98.28% w/w and 72.52-92.74% w/w, respectively. Calcium-gellan beads containing diclofenac sodium showed pH-dependent swelling and drug release properties. Swelling and drug release were significantly higher in pH 7.4 phosphate buffer than 0.1N HCl. The swelling ratio for beads was up to 22 and 3 for phosphate buffer and 0.1N HCl, respectively. Cumulative diclofenac sodium release from calcium-gellan beads was 12-35% in 0.1N HCl within 2 h, whereas complete drug release was observed within 3-4 h in pH 7.4 phosphate buffer.     

Development of novel gastroretentive drug delivery system of gliclazide: hollow beads

Aim: The current communication deals with the development of hollow floating beads of gliclazide. The primary effect of this drug is to potentiate glucose-stimulated insulin release from pancreatic islet-β-cells by induction of a decrease in potassium efflux from these cells. Because of the poor aqueous solubility, its absorption is limited. Thus, an attempt was made to improve its release profile.

Methods: The hollow drug-loaded alginate beads in combination with low methoxyl pectin and hydroxypropylmethylcellulose (HPMC) were prepared by a simple ionotropic gelation method. The beads were evaluated for particle size and morphology using optical microscopy and scanning electron microscopy (SEM), respectively. Mucoadhesion test was done using goat stomach mucosal membrane. Release characteristics of the gliclazide-loaded hollow beads were studied in 0.1?N HCl (pH 1.2) and phosphate buffer (pH 5.8).

Results: The developed beads were spherical in shape with hollow internal structure and had a particle size in the range of 0.730?±?0.05 to 0.890?±?0.03?mm. The incorporation efficiency of alginate -pectin beads was higher than alginate -HPMC beads. The Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction analysis showed stable character of drug in the drug-loaded hollow beads and revealed the absence of any drug -polymer interactions. The beads remained buoyant for more than 12?h. The drug release from beads followed Fickian diffusion with swelling.

Conclusion: The preliminary results of this study suggest that the developed beads containing gliclazide could enhance drug entrapment efficiency, reduce the initial burst release and modulate the drug release.     

Adsorption and recovery of lead(II) from aqueous solutions by immobilized Pseudomonas Aeruginosa PU21 beads

In this study, immobilized Pseudomonas aeruginosa PU21 beads were used as an adsorbent for lead(II). Different weight percentages of chitosan were added to polyethylene glycol (PEG, 0.5 wt.% in aqueous solution) and alginate (18 wt.% in aqueous solution), and then blended or cross-linked using different concentrations of epichlorohydrin (ECH) to prepare beads of different sizes and increased mechanical strength. Before blending or cross-linking, different weight percentages of P. aeruginosa PU21 were added to increase lead(II) adsorption. Subsequently the optimized bead composition (concentration of ECH, percentages of chitosan and P. aeruginosa PU21) and the optimum adsorption conditions (agitation rate and pH in the aqueous solution) were ascertained. Finally, the optimized beads adsorbing lead(II) were regenerated by 0.1M aqueous HCl solutions and the most effective desorption agitation rate was ascertained. The results indicate that the reuse of immobilized P. aeruginosa PU21 beads was feasible. In addition, the equilibrium adsorption, kinetics, changes in the thermodynamic properties of adsorption of lead(II) on optimized beads were also investigated.     

Avicel RC-591/Chitosan Beads by Extrusion-Spheronization Technology

Beads were successfully prepared using the combination of Avicel RC-591 and chitosan using extrusion and spheronization technology. The effects of different viscosity grades of chitosan (SEACURE 142, 242, 342 and 442) on bead formation and on release profiles were examined using acetaminophen as a model drug. Incorporation of higher viscosity grades of chitosan yielded beads with rough surfaces and slower release characteristics. Seacure 342 was chosen for further studies using acetaminophen and theophylline as model drugs of different solubilities. Beads were prepared with varying proportions of Seacure 342 and Avicel RC-591 (20% drug loading). Drug release from the beads varied with the dissolution method used. Beads were swollen in 0.1 N HC1 while the bead structure remained intact. In water, the beads exhibited gel-like structures.     

Controlled release multiple layer coatings

Purpose: In a fluid-bed coating machine, the coating solutions are normally sprayed using a manually controlled peristaltic pump. This study provides a process where two or more coating solutions can be sprayed consecutively using two or more syringe pumps controlled by a computer, to form multiple layers. In this process, the spraying parameters can be controlled easily from a computer. Methods: Propranolol HCl was used as a model drug. Nine different drug-loaded controlled release coated beads were prepared by using a combination of ethylcellulose and/or chitosan solutions. The pulse-coated beads were prepared by changing the spray rate and/or volume of the polymer solutions. Results: There was a fourfold increase (18 versus 75 minutes) in lag time when the same amount of ethylcellulose (4 g) was dissolved in 100 mL of ethanol instead of 160 mL. When the same amount of drug and ethylcellulose solution was applied on the acrylic coated beads as multiple layers coating, the lag time decreased to only 6 minutes. Similarly, the 50% drug release time also decreased significantly. Conclusion: An overall comparison of the dissolution profiles showed that drug release from these coated beads was changed significantly when the sequence of the drug and polymer layers was changed.     

Thymopentin-loaded pH-sensitive chitosan nanoparticles for oral administration: preparation, characterization, and pharmacodynamics

Thymopentin, a potent immunomodulating drug, was incorporated into pH-sensitive chitosan nanoparticles prepared by ionic gelation of chitosan with tripolyphosphate anions and then coated with Eudragit S100 to improve the stability and the oral bioavailability. Nanoparticles particle size and zeta potential were measured by photo correction spectroscopy and laser Dopper anemometry. Its morphology was examined by environment scan electron microscope. The encapsulation efficiency and the release in vitro were determined by HPLC. Enzymatic stabilization was expressed by the enzymatic degradation of aminopeptidase. Biological activity of TP5 loaded in nanoparticles was assayed by lymphocyte proliferation test in vitro and the immune function (CD4+/CD8+) of irradiated rat in vivo. The results obtained demonstrated that the average sizes of pH-sensitive chitosan nanoparticles were 175.6 +/- 17 nm, the zeta potential was 28.44 +/- 0.5 mV and the encapsulation efficiency was 76.70 +/- 2.6%. The cumulative release percentages of thymopentin from the pH-sensitive nanoparticles were 24.65%, 41.01%, and 81.44% incubated in different medium, 0.1 N HCl, pH 5.0 PBS, and pH 7.4 PBS, respectively. The pH-sensitive chitosan nanoparticles could efficiently protect TP5 from enzymatic degradation and prolong the degradation half-time of TP5 from 1.5 min to 15 min. It was demonstrated from the lymphocyte proliferation test that the nanoparticle-encapsulated TP5 still kept its biological activity. In immunosuppression rats, the lowered T-lymphocyte subsets values were significantly increased and the raised CD4+/CD8+ ratio was evidently reduced. These results indicated that pH-sensitive chitosan nanoparticles may be used as the vector in oral drug delivery system for TP5.     

Preparation and Evaluation of Controlled Release Propranolol Hydrochloride Beads

Conventional pan coating method was utilized to prepare propranolol-HCl sustained release coated beads. Eudragit RS 100 was used as release controlling materials. Overcoating of the beads with beeswax was also investigated. The beads were characterized for their particle size distribution, drug loading efficiency and their dissolution behaviour in 0.1N HCl, Most of the finished beads (72.4%) fall in the particle size range 800-1700 um. The actual drug content, calcu-lated as opposed to the theoretical drug content were 77.6% and 74.2% of the drug for the beads having particle size range 1700-1250 um and 1250-800 um respectively, The coating level of the polymer, the particle size of the beads and overcoating with beeswax play a major role in determining the release rate of the drug from the coated beads.     

Avicel RC-591/Chitosan Beads by Extrusion-Spheronization Technology

Abstract

Beads were successfully prepared using the combination of Avicel RC-591 and chitosan using extrusion and spheronization technology. The effects of different viscosity grades of chitosan (SEACURE 142, 242, 342 and 442) on bead formation and on release profiles were examined using acetaminophen as a model drug. Incorporation of higher viscosity grades of chitosan yielded beads with rough surfaces and slower release characteristics. Seacure 342 was chosen for further studies using acetaminophen and theophylline as model drugs of different solubilities. Beads were prepared with varying proportions of Seacure 342 and Avicel RC-591 (20% drug loading). Drug release from the beads varied with the dissolution method used. Beads were swollen in 0.1 N HC1 while the bead structure remained intact. In water, the beads exhibited gel-like structures.     

Preparation and Evaluation of Controlled Release Propranolol Hydrochloride Beads

Abstract

Conventional pan coating method was utilized to prepare propranolol-HCl sustained release coated beads. Eudragit RS 100 was used as release controlling materials. Overcoating of the beads with beeswax was also investigated. The beads were characterized for their particle size distribution, drug loading efficiency and their dissolution behaviour in 0.1N HCl, Most of the finished beads (72.4%) fall in the particle size range 800–1700 um. The actual drug content, calcu-lated as opposed to the theoretical drug content were 77.6% and 74.2% of the drug for the beads having particle size range 1700–1250 um and 1250–800 um respectively, The coating level of the polymer, the particle size of the beads and overcoating with beeswax play a major role in determining the release rate of the drug from the coated beads.     

Biodegradable IPN hydrogel beads of pectin and grafted alginate for controlled delivery of diclofenac sodium

A novel diclofenac sodium (DS) loaded interpenetrating polymer network (IPN) beads of pectin and hydrolyzed polyacrylamide-graft-sodium alginate (PAAm-g-SA) was developed through ionotropic gelation and covalent cross-linking. The graft copolymer was synthesized by free radical polymerization under the nitrogen atmosphere followed by alkaline hydrolysis. The grafting, alkaline hydrolysis, and characterization of beads were confirmed by Fourier transforms infrared spectroscopy. The crystalline structure of drug after encapsulation into IPN beads were evaluated by differential scanning colorimetry and X-ray diffraction analyses. DS encapsulation was up to 96.45 %. The effect of hydrolyzed graft copolymer/pectin ratios and glutaraldehyde concentration on drug release in acidic and phosphate buffer solutions were investigated. The release of drug was significantly increased with increase of pH. The release of drug depends on the extent of cross-linking. The results indicated that IPN beads of hydrolyzed PAAm-g-SA and pectin could be used for sustained release of DS.     

Quaternized chitosan (QCS) nanoparticles as a novel delivery system for ammonium glycyrrhizinate

The aim of this study was to generate a new type of nanoparticles made of quaternized chitosan (QCS) and poly(aspartic acid) via the ionotropic gelation technique and to evaluate their potential for the association and delivery of ammonium glycyrrhizinate (GLA). The effects of the pH value of nanoparticles, QCS molecular weight (Mw) and poly(aspartic acid) concentration on GLA encapsulation were studied. Suitably pH value of nanoparticles, moderate QCS MW, optimal concentration ratio of poly(aspartic acid) and QCS favored higher GLA encapsulation efficiency. The release of GLA from nanoparticles was pH-dependent. Fast release occurred in 0.1 M phosphate buffer solution (PBS, pH = 7.4), while the release was slow in 0.1 M HCl (pH = 1.2). The results showed that the new QCS/poly(aspartic acid) nanoparticles have a promising potential in GLA delivery system.     

Synthesis,Characterization and Drug Release Behavior of pH‐Responsive O‐carboxymethyl Chitosan‐graft‐poly(N‐vinylpyrrolidone) Hydrogel Beads

In this work, the carboxymethyl chitosan (CMCTS) grafted poly(N‐vinylpyrrolidone) (PVP) copolymers were synthesized. The hydrogel beads containing VB₂ were prepared from the copolymers by an ionic crosslinked. The experimental results shown that VB₂ drug release rate from those beads decreased with the increasing grafting percentage, crosslinker concentration and pH value of the medium. Besides, the beads have the better control ability for releasing of model drug than CMCTS does.     

Formulation and corneal permeation of ketorolac tromethamine-loaded chitosan nanoparticles

Abstract

The aim of this work was to formulate chitosan (CS)-based nanoparticles (NPs) loaded with ketorolac tromethamine (KT) intended for topical ocular delivery. NPs were prepared using ionic gelation method incorporating tri-polyphosphate (TPP) as cross-linker. Following the preparation, the composition of the system was optimized in terms of their particle size, zeta potential, entrapment efficiency (EE) and morphology, as well as performing structural characterization studies using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The data suggested that the size of the NPs was affected by CS/TPP ratio where the diameter of the NPs ranged from 108.0?±?2.4?nm to 257.2?±?18.6?nm. A correlation between drug EE and the corresponding drug concentration added to the formulation was observed, where the EE of the NPs increased with increasing drug concentration, for up to 10?mg/mL. FT-IR and DSC revealed that KT was dispersed within the NPs where the phosphate groups of TPP were associated with the ammonium groups of CS. The in vitro release profile of KT from CS NPs showed significant differences (p?<?0.05) compared to KT solution. Furthermore, mucoadhesion studies revealed adhesive properties of the formulated NPs. The KT-loaded NPs were found to be stable when stored at different storage conditions for a period of 3 months. The ex vivo corneal permeation studies performed on excised porcine eye balls confirmed the ability of NPs in retaining the drug on the eye surface for a relatively longer time. These results demonstrate the potential of CS-based NPs for the ocular delivery of KT.     

Hydroxybutyl chitosan thermo-sensitive hydrogel: a potential drug delivery system

Drug delivery mediated by hydrogel has shown great promise in controlled drug release field. We report here the development of a hydroxybutyl chitosan (HBC) thermo-sensitive gel to deliver doxorubicine hydrochloride (DOX·HCl) for cancer treatment. Concentrated HBC aqueous solution could transform into hydrogel within 30 s after injection under physiological temperature in non-chemical fashion. The properties of the HBC gels including chemical structure, surface morphology, and rheologic properties were studied. Gelation temperature and gelation time of HBC could be adjusted by HBC concentrations. The gel erosion rate in vivo was faster than solubilization rate in vitro. The mild inflammatory response caused by implantation of the hydrogel was acceptable. The DOX·HCl (1 mg/ml) loaded HBC gels displayed slow release rates that were independent of the HBC concentration, and significantly reduced viability of 4T-1 cells compared with the HBC gels after 1 day incubation. These results indicate that thermo-sensitive HBC hydrogels have promising potential as an injectable drug carrier for pharmaceutical applications.     

不同引发剂体系对氧化铝浆料固化过程的影响

研究了引发剂体系对氧化铝浆料固化过程的影响. 通过测试丙烯酰胺(AM)水溶液聚合过程的弹性模量曲线, 考察了引发剂体系对丙烯酰胺(AM)和N,N’-亚甲基双丙烯酰胺 (MBAM)水溶液交联聚合过程的影响. 引发剂体系分别为过硫酸铵(APS)、过硫酸铵-四甲基乙二胺(APS-TEMED)氧化还原体系和2,2’-偶氮[2-(2-咪唑啉-2-基)丙烷]盐酸盐(AZIP·2HCl). 三种引发剂中AZIP\cdot2HCl引发的聚合产物的模量在40～50℃都比较高; 温度对闲置时间影响较大, 更容易控制固化进程. AZIP·2HCl引发的50vol%浆料固化的模量曲线表明温度和引发剂浓度对浆料固化影响较大. 比较了三种引发剂引发的50vol%氧化铝浆料的固化过程模量曲线, 50℃时AZIP·HCl引发的浆料固化后的湿坯的弹性模量达到2.3×10⁶Pa, 比APS(1.58×10⁶Pa,55℃)和APS--TEMED(1.58×10⁶Pa, 25℃)引发的浆料固化后的湿坯模量要高.     

Removal of fluoride from aqueous solution using protonated chitosan beads

In the present study, chitosan in its more usable bead form has been chemically modified by simple protonation and employed as a most promising defluoridating medium. Protonated chitosan beads (PCB) showed a maximum defluoridation capacity (DC) of 1664mgF-/kg whereas raw chitosan beads (CB) possess only 52mgF-/kg. Sorption process was found to be independent of pH and altered in the presence of other co-existing anions. The sorbents were characterized using FTIR and SEM with EDAX analysis. The fluoride sorption on PCB follows both Freundlich and Langmuir isotherms. Thermodynamic parameters, viz., DeltaG degrees , DeltaH degrees DeltaS degrees and Ea indicate that the nature of fluoride sorption is spontaneous and endothermic. The sorption process follows pseudo-second-order and intraparticle diffusion kinetic models. 0.1M HCl was identified as the best eluent. The suitability of PCB has been tested with field samples collected from a nearby fluoride-endemic area.     

Effect of Chitosan-Coated Alginate Microspheres on the Permeability of Caco-2 Cell Monolayers

ABSTRACT

Alginate microspheres were prepared by emulsification/internal gelation and coated with chitosan. The ability of chitosan-coated alginate microspheres to increase the paracellular transport across Caco-2 cell monolayers was evaluated in comparison to uncoated microspheres and chitosan solutions. Transport studies were performed by using a permeability marker, Lucifer Yellow (LY), and by measuring the transepithelial electric resistance (TEER) variations. Furthermore, the occurrence of cytotoxic effects was assessed by evaluating neutral red uptake in viable cells and lactate dehydrogenase (LDH) release from damaged cells. A 3-fold increase on LY permeability was obtained for coated microspheres when compared to chitosan solutions. TEER variations were in agreement with permeability results. Chitosan solutions exhibited a dose-dependent toxicity, but coated microspheres did not decrease the viability of cells. Chitosan-coated alginate microspheres have potential to be used as carriers of poorly absorbable hydrophilic drugs to the intestinal epithelia and possibly increase their oral bioavailability.