Graphene oxide/poly(<Emphasis Type="Italic">N</Emphasis>-isopropyl acrylamide)/sodium alginate-based dual responsive composite beads for controlled release characteristics of chemotherapeutic agent

In this work, graphene oxide (GO)-incorporated composite beads were developed from poly(N-isopropyl acrylamide)/sodium alginate (PNIPAM/NaAlg) using ionotropic gelation technique. The interaction between GO and PNIPAM/NaAlg with Ca²⁺ ions as a cross-linker was investigated by Fourier transform spectroscopy. X-Ray diffraction pattern showed that the GO was distributed uniformly in the PNIPAM/NaAlg with Ca²⁺ ions while scanning electron micrograph technique revealed that composite beads were formed in spherical shape. The controlled release characteristics of composite beads were studied using 5-fluorouracil (5-FU) as anti-cancer model drug. The encapsulation efficiencies were found to be between 90 and 92% in all formulations. Furthermore, the equilibrium swelling ratio (%) and in vitro release studies of the beads were carried out in two different pH values of 1.2 and 7.4 and at different temperature conditions of 25 and 37 °C. The obtained results showed that the swelling ratio decreased with an increase in GO concentration. In vitro release studies performed in response to both pH and temperature and they proved that the 5-FU drug was released from composite beads over 32 h without burst release. Cytotoxicity results showed pristine composite beads are good cytocompatible. In addition, the cytotoxicity of 5-FU was found to be improved when incorporated with composite beads than pure 5-FU. It is therefore concluded that the developed composite beads have dual response and can be used as controlling released carriers in cancer drug delivery applications.     

Controlled release of chlorpheniramine maleate through IPN beads of sodium alginate‐g‐methylmethacrylate

Controlled release of chlorpheniramine maleate drug, through sodium alginate‐g‐methylmethacrylate (NaAlg‐g‐MMA) interpenetrating polymeric network beads, has been investigated. Beads were prepared by precipitating the viscous solution of NaAlg‐g‐MMA in acetone followed by cross‐linking with glutaraldehyde. The beads were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Different formulations of beads were developed by varying amounts of MMA, cross‐linking agent, and drug concentration. DSC thermograms of chlorpheniramine maleate drug‐loaded NaAlg‐g‐MMA beads confirmed the molecular level distribution of drug in the polymer matrix. FTIR of beads confirm the grafting and cross‐linking, SEM of the beads suggested the formation of spherical particles. Swelling experiments on the beads provided an important information on drug diffusion properties. Release data have been analyzed using an empirical equation to understand the nature of transport of drug containing solution through the polymeric matrices. The controlled release characteristics of the matrices for chlorpheniramine maleate was investigated in pH 7.4 media. Drug was released in a controlled manner upto 12 h. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Semiinterpenetrating polymer networks of chitosan and L‐alanine for monitoring the release of chlorpheniramine maleate

In vitro studies have been carried on semiinterpenetrating polymer network (IPN) beads of chitosan–alanine as carrier for the controlled release of chlorpheniramine maleate (CPM) drug. A viscous solution of chitosan–alanine was prepared in 2% acetic acid solution, extruded as droplets by a syringe to NaOH–methanol solution and crosslinked using glutaraldehyde as a crosslinker. The swelling behavior of crosslinked beads in different pH solutions was measured at different time intervals. The swelling behavior was observed to be dependent on pH and degree of crosslinking. The structural and morphological studies of beads were carried out by using a scanning electron microscope. The drug release experiments of different drug loading capacity beads were performed in solutions of pH 2 and pH 7.4 using CPM as a model drug. The concentration of the released drug was evaluated using UV spectrophotometer. The results suggest that chitosan–alanine crosslinked beads are suitable for controlled release of drug. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3751–3757, 2007     

On the encapsulation of natural pesticide using polyvinyl alcohol/alginate–montmorillonite nanocomposite for controlled release application

A representative pesticide, NeemAzal was encapsulated into polyvinyl alcohol/alginate‐montmorillonite (PVA/Alg‐MMT) nanocomposite by cross‐linking with glutaraldehyde. Different formulations of capsule beads containing NeemAzal were prepared with different concentration of materials. Evidence of cross‐linking of PVA and Alg was obtained by comparison of the Fourier transform infrared spectra of the initial substrates and capsule beads. X‐ray diffraction and transmission electron microscopy techniques confirmed the intercalated structure of capsule bead nanocomposites. In addition the swelling behavior of capsule beads was investigated. Results showed that swelling ratio of capsule beads decreases with introduction of MMT as well as increase of PVA content in capsule bead formulations. The release characteristics of NeemAzal from capsule beads were monitored using UV–visible spectrophotometer in distilled water. The addition of sodium MMT to these formulations was found to have a profound inhibitory effect on the release of NeemAzal. Furthermore, the release data were fitted to several empirical equations to estimate the kinetic parameters. The NeemAzal encapsulated PVA/Alg‐MMT nanocomposite capsule beads, designed and discussed in this work, have the potential for controlled release of pesticide. POLYM. ENG. SCI., 54:2707–2714, 2014. © 2013 Society of Plastics Engineers     

Controlled release study of carbaryl insecticide from calcium alginate and nickel alginate hydrogel beads

In this study, controlled release formulations for reducing environmental impact of pesticides have been produced by encapsulating as a model pesticide carbaryl (Carb) in the alginate beads. The various hydrogel bead formulations were prepared by the ionotropic crosslinking of sodium alginate (NaAlg) with calcium and nickel ions. The surface morphology of prepared beads was characterized with scanning electron microscopy (SEM). SEM confirmed the spherical nature and surface morphology of the particles. Bead characteristics, such as carbaryl entrapment efficiency, particle size, equilibrium swelling degree, and carbaryl release kinetics, were determined. The effects of the bead preparation conditions such as crosslinker concentration and type, carbaryl/sodium alginate (Carb/NaAlg) ratio and percentage of NaAlg on the carbaryl release from the calcium alginate (Ca‐Alg) and nickel alginate (Ni‐Alg) beads were investigated in distilled water at 25°C. It was observed that carbaryl release from the Ca‐Alg beads was slower than that of Ni‐Alg beads. The release results indicated that carbaryl release from both of the Ca‐Alg and Ni‐Alg beads decreases with the increasing crosslinker concentration, Carb/NaAlg ratio and percentage of NaAlg. The highest carbaryl release was found to be 100% for the Ni‐Alg beads at 3 days whereas the lowest carbaryl release was found to be 67% for the Ca‐Alg beads at 21 days. The swelling measurements of the beads were also in consistent with the carbaryl release results. The carbaryl release from most of the bead formulations followed Case II transport. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Semi‐interpenetrating polymer network beads of crosslinked chitosan–glycine for controlled release of chlorphenramine maleate

Spherical, semi‐interpenetrating polymer network beads of chitosan and glycine, crosslinked with different concentrations of glutaraldehyde were prepared for controlled release of drugs. The structural and morphological studies of the beads were carried out with FTIR and SEM techniques. The swelling behavior of the beads at different time intervals was monitored in solutions of different pH. Structural changes of the beads in response to solution pH were put forward using the data obtained from IR/UV spectral analysis. The release experiments were performed in solutions of pH 2.0 and pH 7.4 at 37°C, using chlorphenramine maleate as a model drug. The results indicate that, chitosan might be useful as a vehicle for controlled release of drugs. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 672–683, 2000     

Sodium alginate polymeric floating beads for the delivery of cefpodoxime proxetil

Sodium alginate (SA) floating beads containing cefpodoxime proxetil, a third‐generation cephalosporin antibiotic, were prepared by precipitation method using calcium carbonate as gas generating agent.Hydroxypropyl methylcellulose (HPMC) was used in all the four formulations in different proportions (F1, F2, F3, and F4) as swelling agent to control the release of the drug. Gas generating agent forms pores on the surface of the beads because of the rapid escape of CO₂ during the curing process in precipitating media. Scanning electron microscopy confirmed their porous and grossly spherical structure, and the size of the beads were in the range of 700–1000 μm. The size of the beads increases with the increase in the concentration of gas‐forming agent and decreases with the increase in the concentration SA. The drug entrapment efficiency was found to be in the range of 85.3–91.1%. F2 shows least entrapment, whereas F3 shows maximum entrapment. The percentage porosity was 82.1–89.1%, and the mean pore diameter was 0.41–0.52 μm. The porosity depends on the concentration of gas‐forming agent. The mechanical strength of the beads was 591–1073 g. All the formulations showed good floating time. The in vitro release was performed in glycine dissolution media according to USP for about 12 h. The cumulative % drug release was found to be 67.5–87.3%. The in vitro dissolution study reveals that the concentration of the gas generating agent and SA affects the release rate. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Studies on semi‐interpenetrating polymer network beads of chitosan–poly(ethylene glycol) for the controlled release of drugs

Semi‐interpenetrating polymer network beads of chitosan and poly(ethylene glycol) were prepared and characterized for controlled release of drugs. A viscous solution of chitosan and poly(ethylene glycol) in 2% acetic acid was extruded as droplets with the help of a syringe and crosslinked using glutaraldehyde. The structural studies of the beads were performed by using a Fourier transform infrared spectrophotometer and scanning electron microscope. The swelling behavior, solubility, hydrolytic degradation, and loading capacity of the beads for isoniazid were investigated. The structural changes of the beads at pH 2.0 and 7.4 were put forward using the data obtained by infrared and ultraviolet spectroscopy. The prepared beads showed 82% drug‐loading capacity, which suggested that these semi‐interpenetrating polymer network beads are suitable for controlled release of drugs in an oral sustained delivery system. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 639–649, 2001     

Controlled release formulations of carbaryl based on copper alginate,barium alginate,and alginic acid beads

A controlled release system for reducing environmental impact was produced by encapsulating the pesticide carbaryl (Carb) in the alginate beads. The various bead formulations were prepared by using sodium alginate (NaAlg) as a polymer, CuCl₂, BaCl₂ as a crosslinking agent, and HCl as a linking agent. The surface morphology of prepared beads was characterized with scanning electron microscopy (SEM). SEM confirmed the spherical nature and surface morphology of the particles. Bead characteristics, such as Carb entrapment efficiency, particle size, swelling degree, and Carb release kinetics, were determined. The effects of crosslinker or linker concentration, type, and carbaryl/sodium alginate (Carb/NaAlg) ratio on Carb release from the beads were investigated for 20 days at 25°C. It was observed that Carb release from the beads increased with the increase of Carb/NaAlg ratio whereas decreased with the increase of crosslinker concentration. At the end of 20 days, the Carb release from alginic acid beads was found to be higher than that of copper alginate (Cu‐Alg) and barium alginate (Ba‐Alg) beads. The swelling measurements of the beads supported the release results. Release kinetics were described by Fickian and non‐Fickian approaches. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 4245–4253, 2006     

Glutaraldehyde‐crosslinked chitosan beads for controlled release of diclofenac sodium

An inexpensive and simple method was adopted for the preparation of chitosan beads, crosslinked with glutaraldehyde (GA), for the controlled release of diclofenac sodium (DS). The beads were prepared by varying the experimental conditions such as pH, temperature, and extent of crosslinking. The absence of any chemical interaction among drug, polymer, and the crosslinking agent was confirmed by FTIR and thermal analysis. The beads were characterized by microscopy, which indicated that the particles were in the size range of 500–700 μm and SEM studies revealed smooth surface and spherical shape of beads. The beads produced at higher temperature and extended exposure to GA exhibited lower drug content, whereas increased drug loading resulted in enhanced drug release. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 211–217, 2007     

Controlled release of diclofenac sodium and ibuprofen through beads of sodium alginate and hydroxy ethyl cellulose blends

Controlled release of diclofenac sodium (DS) and ibuprofen (IB) drugs through sodium alginate (NaAlg)‐hydroxy ethyl cellulose (HEC) blend polymeric beads has been investigated. Beads were prepared by precipitating the viscous solution of NaAlg and HEC blend in alcohol followed by crosslinking with calcium chloride. Different formulations were developed in bead form by varying the amount of HEC, crosslinking agent, and drug concentration. Swelling studies in water, percent encapsulation of drugs, and release studies were carried out. The DS‐loaded beads have shown better release performance than the IB‐loaded beads. Diffusion parameters were evaluated from the Fickian diffusion theory. Mathematical modeling studies and drug release characteristics through bead matrices were studied by solving Fick's diffusion equation. The results are discussed in terms of drug release patterns and theoretical concentration profiles generated through matrices, considering spherical geometry of the beads. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 5708–5718, 2006     

Barium Ions Crosslinked Alginate and Sterculia Gum-Based Gastroretentive Floating Drug Delivery System for Use in Peptic Ulcers

The gastro-retentive drug delivery system is required to improve the bioavailability and therapeutic efficacy of the drugs used for the diseases associated with the stomach. Both sterculia gum and alginate enhance the repair of mucosal damage in the GI tract and pantoprazole is a therapeutic agent for GI tract ulcers. Ionotropic gelation of these polysaccharides for the release of pantoprazole will develop the double potential drug delivery systems. Therefore, in the present study, an attempt has been made to synthesize a gastro-retentive floating drug delivery system by simultaneous ionotropic gelation of alginate and sterculia gum using BaCl₂ as a crosslinker. The beads have been characterized by SEMs, EDAX, and FTIR analysis. The swelling of beads has been carried out as a function of pH of the swelling media. In addition, in vitro release dynamics of an anti-ulcer model drug pantoprazole from drug-loaded beads in different release media have been carried out for the evaluation of the drug release mechanism and diffusion coefficients. Release of drug from beads occurred through a Fickian-type diffusion mechanism. The present drug delivery sytem may have a double potential, first due to the therapeutic importance of the sterculia–alginate-based polymer matrix and second, release of pantoprazole in a controlled and sustained manner.     

Development of Bigels Based on Stearic Acid–Rice Bran Oil Oleogels and Tamarind Gum Hydrogels for Controlled Delivery Applications

In the last few decades, different types of gels have been widely studied as potential drug delivery carriers. In this paper, we propose the synthesis of an oleogel, a tamarind gum hydrogel, and bigels for applications as drug delivery matrices. The oleogel was prepared by mixing stearic acid and rice bran oil, whereas the hydrogel was prepared by mixing tamarind gum with a hydroethanolic solution. Hydrogel‐in‐oleogel and oleogel‐in‐hydrogel bigels were prepared by mixing the hydrogel and the oleogel. The suitability of the formulations for controlled drug release applications was thoroughly examined using microscopy, Fourier transform infrared (FTIR) spectroscopy, as well as mechanical, electrical, thermal, drug release, and antimicrobial studies. An alteration in the microarchitecture of the bigels is observed when the oleogel and the hydrogel are mixed in varying proportions. The associative interactions within the formulations increase with the increase in the hydrogel content. The bigels exhibit the presence of stearic acid melting endotherm (associated with the oleogel) and water evaporation endotherm (associated with the hydrogel). This study suggests that the hydrogel has lowest bulk resistance compared to the other formulations. The structural breakdown of the bigels is composition‐dependent, and the bulk electrical resistance is mainly governed by the oleogel phase. An increase in the diffusion of the moxifloxacin HCl from the formulations is observed with the increase of the hydrogel proportion, which in turn increases the rate of release of the drug. The proposed formulations also exhibit good antimicrobial efficacy. The analysis of these properties suggests that specific formulations can be tailored by need‐based applications of the drug release rate.     

Controlled delivery of diclofenac sodium from calcium alginate beads loaded with a drug–resin complex

This study focused on a detailed investigation of the release of the nonsteroidal anti‐inflammatory drug diclofenac sodium from strong anion resin particles, entrapped in ionotropically crosslinked alginate beads, in simulated gastric and intestinal fluids at 37°C. The percentage drug released from the beads in media of various pH values in 6 h was nearly 68.8 ± 2.6%, whereas, for the same duration, the drug–resin complex particles released 87.6 ± 3.2% drug. The amount of drug released from the beads depended on the composition of the beads, their degree of crosslinking, and the size of the crosslinker ions. Finally, the value of the release exponent was found to be 0.56, which thus indicated the diffusion‐controlled mechanism of drug release from the alginate beads © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Dual responsive polymeric bionanocomposite gel beads for controlled drug release systems

Scientists are searching potential solutions for cancer treatments as well as ways to avoid the side effects of anti‐cancer agents, via targeted drug delivery. The aim of this research is to propose dual responsive beads based on sodium alginate (SA), methylcellulose (MC), and magnetic iron oxide nanoparticles (MIONs) for controlled release of 5‐Fluorouracil (5‐FU) as model drug. The beads were prepared by the dual crosslinking of SA and MC in the presence of MIONs. The structural, thermal, morphological, magnetic characteristics as well as the release profile of 5‐FU were studied. The characterization results showed that the drug molecules and MIONs were well dispersed in the polymeric matrix. The cumulative release percentage was ca. 80% at pH = 4.2 and 40% at pH = 7.2 after 6 h. Thus, the sensitivity of beads on the pH value was verified. Moreover, the release profile exhibited reduction with an increase in the concentration of MIONs under an external magnetic field. The obtained results confirmed the dual sensitive release of 5‐FU (i.e., PH/magnetic) that can be used for the targeted and controlled drug delivery systems. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45143.     

Development,optimization, and evaluation of emulsion‐gelled floating beads using natural polysaccharide‐blend for controlled drug release

This article describes the development, optimization, and evaluation of groundnut oil‐entrapped tamarind seed polysaccharide (TSP)‐alginate floating beads containing diclofenac sodium by emulsion‐gelation method for gastroretentive delivery. The effect of polymer to drug ratio, groundnut oil to water ratio, and sodium alginate to TSP ratio on drug entrapment, density, and drug release of floating beads was optimized using three‐factor and two‐level factorial design. The optimized floating beads showed drug entrapment efficiency of 82.48% ± 2.34%, density of 0.88 ± 0.07 g/cm³, cumulative drug release of 41.02% ± 0.86% after 8 h and floated well over 8 h in simulated gastric fluid (pH 1.2) with 8.25 min floating lag‐time. The in vitro drug release from these floating beads containing diclofenac sodium was followed controlled‐release pattern (zero‐order kinetics) with case‐II transport mechanism. The average bead size was ranged from 1.07 ± 0.03 to 1.94 ± 0.09 mm. The floating beads were characterized by SEM, FTIR, and ¹H NMR. The optimized floating beads showed excellent anti‐inflammatory activity in carrageenan‐induced rats over prolonged period after oral administration. POLYM. ENG. SCI., 2013. © 2012 Society of Plastics Engineers     

Drug Release Kinetics and Mechanism from PLGA Formulations

The release kinetics of indomethacin (IND) and hydrochlorothiazide (HCT) from drug/PLGA formulations with different copolymer composition and molecular weight of PLGA were measured in vitro by using a rotating disk system (USP II). The release mechanism of IND and HCT from their PLGA formulations was analyzed using a chemical‐potential‐gradient model combined with the Perturbed‐Chain Statistical Associating Fluid Theory (PC‐SAFT). Furthermore, the release kinetics of IND and HCT from the PLGA formulations with different copolymer composition and molecular weight of PLGA were correlated and predicted in good accordance with the experimental data. It was found that the chemical‐potential‐gradient model combined with the PC‐SAFT helped to understand the drug release mechanism from the drug/PLGA formulations. It also well correlated and predicted the drug release kinetics as function of copolymer composition and molecular weight of PLGA as well as of drug type. It helps to save time and costs for determination of the long‐term drug release kinetics, especially for sustained drug release as obtained from the drug/PLGA formulations in this work. © 2016 American Institute of Chemical Engineers AIChE J, 62: 4055–4065, 2016     

Effects of Drying Methods on the Release Kinetics of Vitamin B12 in Calcium Alginate Beads

The aim of this article was to investigate the morphology, swelling properties, and respective drug release kinetics of vitamin B₁₂–loaded calcium alginate beads prepared by oven (air), vacuum, and freeze drying. The initial particle size was 1 mm. The mean bead sizes of dried Ca-alginate beads were 0.7, 0.8, and 0.9 mm for oven-, vacuum-, and freeze-dried beads, respectively. The surface morphology of the dried beads was affected by the different drying methods applied. Oven- and vacuum-dried beads shrank in size, and more cracks appeared on the surface of oven-dried beads. Freeze-dried beads almost retained the same size prior to drying; however, the surface was rougher and highly porous. The swelling profiles were also affected by the drying methods, whereby freeze-dried beads showed the fastest solvent uptake at the start of the experiment. The release data of the dried Ca-alginate beads were treated with first-order, Higuchi, Korsmeyer, and Peppas kinetic models. The data for oven and vacuum seemed to follow a combination of diffusion and swelling controlled release, whereas data from freeze-dried beads seemed to follow more diffusion-dominated controlled release.     

Microwave-assisted synthesis of alginate-g-polyvinylpyrrolidone copolymer and its application in controlled drug release

The aim of this study is to synthesize graft copolymer (NaAlg-g-PVP) in microwave oven and prepare pH-responsive beads with high entrapment efficiency. For this purpose, PVP was grafted onto sodium alginate using microwave radiation. The copolymer obtained was characterized using FTIR, ¹H-NMR, elemental analysis and thermogravimetric analysis. A series of NaAlg-g-PVP beads were prepared as drug delivery matrices for ibuprofen (IB) by cross-linking into beads via glutaraldehyde. The chemical stability of IB after encapsulation into beads was confirmed by FTIR, DSC, and X-RD analysis. Synthesis conditions of beads were optimized by considering entrapment efficiency, particle size, swelling capacity and their release data. Effects of such variables as graft yield and drug/polymer ratio were investigated at 1.2 and 7.4 pH values. Increasing the drug/polymer ratio and extent of cross-linking caused decrease in the IB release. On the other hand, increase in the graft yield led to increase in the IB release as well. The results also showed that NaAlg-g-PVP beads were positive pH-responsive.     

Sweet Potato Starch Microparticles as Controlled Drug Release Carriers: Preparation and In Vitro Drug Release

The aim of this study was to investigate the in vitro drug release behavior of sweet potato starch (SPS) microparticles intended for controlled drug delivery applications. Diclofenac sodium (DS) was used as a model drug candidate in the present study. SPS microparticles were prepared using a spray-drying technique by varying the polymer concentration and drug loading. The mean particles size of drug-loaded spray-dried SPS microparticles was between 10.3 and 13.1 µm. The mean particle size increased slightly with increase in the concentration of SPS. The mean particle size of spray-dried SPS microparticles increased from 10.3 to 13.1 µm when the concentration of SPS increased from 2 to 4% w/v. Under the current spray-drying conditions, the percentage yield of spray-dried SPS microparticles did not vary much among the various formulations and it was between 65.2 and 70.1%. The encapsulation efficiencies of SPS microparticles formulations was between 95.1–98.2%, suggesting good encapsulating ability of the SPS polymer by spary drying. Drug release from all the formulations of spray-dried SPS microparticles was controlled over period of 6 h. The cumulative amount of drug release from the spray-dried SPS microparticles decreased with an increase in the concentration of SPS, while it increases as the drug loading is increased. Release of the drug from spray-dried SPS microparticles followed Fick's law of diffusion since a good correlation coefficient (R²) was observed with the Higuchi plots (R² = 0.9928 to 0.9979).