Controlled release of naproxen from sodium alginate and poly(vinyl alcohol)/sodium alginate blend beads crosslinked with glutaraldehyde

In this study, polymeric beads of sodium alginate (NaAlg) and its blend with poly(vinyl alcohol) (PVA) were prepared by crosslinking with glutaraldehyde (2.5% v/v) and hydrochloric acid (3% v/v) for the release of naproxen sodium (NS). The prepared beads were characterized with Fourier transform infrared spectroscopy, and pictures of the beads were determined with an optic microscope. The release studies were carried out at three pH values (1.2, 6.8, and 7.4) for 2 h. The effects of the preparation conditions, including the PVA/NaAlg (w/w) ratio, drug/polymer (w/w) ratio, and time of exposure to the crosslinker, on the release of NS were investigated for 10 h at 37°C. The release of NS decreased with the PVA/NaAlg (w/w) ratio and drug/polymer ratio increasing. At the end of 10 h, the highest release of NS was found to be 84% for the 1/2 PVA/NaAlg (w/w) ratio. The swelling measurements of the beads supported the release results. The release kinetics were described with Fickian and non‐Fickian approaches. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation of injectable paclitaxel sustained release microspheres by spray drying for inhibition of glioma in vitro

The major aim of this work was to prepare injectable paclitaxel‐loaded poly(D ,L ‐lactide) microspheres for the inhibition of brain glioma. Paclitaxel‐loaded PLA microspheres were prepared by spray drying method employing ethyl acetate as solvent. And the microspheres were characterized by scanning electron microscopy (SEM) for the morphology and differential scanning calorimetry for thermal analysis. The encapsulation efficiency (EE) and in vitro release profiles of paclitaxel‐loaded microspheres were determined by using ultraviolet spectrophotometer. The results showed that the microspheres possess a narrow size distribution with the average diameter of 4.6 μm. The surface of the microspheres was smooth, and the paclitaxel dispersed in microspheres in amorphous state. The solvent residue was 0.03%, and the EE reaches ～ 90%. The microspheres exhibited a sustained release behavior, and the release period last for at least three months, depending on the EE of the microspheres. The γ irradiation sterilization had little effect on the EE and drug release in vitro. Compared with the commercial formulation, the sustained release microsphere showed a stronger inhibition on the tumor cells, suggesting the potential application of long‐term delivery of paclitaxel‐loaded PLA microspheres in clinic tumor therapy. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

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     

Polyanhydride microspheres as drug carriers. II. Microencapsulation by solvent removal

A new method to prepare polyanhydride microspheres, namely via solvent removal, is presented. Polyanhydrides composed of the following diacids were used: sebacic acid (SA), bis(p-carboxy-phenoxy) propane (CPP), and dodecanedioic acid (DD). Polymers were characterized by infrared (IR) spectroscopy, X-ray diffraction, viscosity, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Drug release was affected by polymer composition, physical properties of the microspheres, and type of drug. The potential for injectable microspheres (size range 1–300 μm) made of copolymer (CPP-SA 50:50), as biodegradable polymer carriers for the controlled release of insulin in treating diabetes mellitus, was assessed. Both 5% and 10% w/w insulin-loaded microspheres were prepared. The 10% loaded microspheres produced the best clinical response, demonstrating five days of urine glucose control and four days of serum glucose control in diabetic rats.     

In vitro release study of diltiazem hydrochloride from poly(vinyl pyrrolidone)/sodium alginate blend microspheres

Polymeric blend microspheres of poly(vinyl pyrrolidone) (PVP) with sodium alginate (NaAlg) were prepared by cross‐linking with calcium ions and used to deliver a calcium channel blocker drug, diltiazem hydrochloride (DT). The prepared microspheres were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. Scanning electron microscopy confirmed the spherical nature of the particles. Preparation conditions for the microspheres were optimized by considering the percentage entrapment efficiency, particle size, and swelling capacity. Effects of variables such as PVP/NaAlg ratio, molecular weight of PVP, cross‐linker concentration, and drug/polymer ratio on the release of DT were discussed at two different pH values (1.2, 6.8) at 37°C. It was observed that DT release from the microspheres decreased with increasing molecular weight of PVP and extent of cross‐linking. However, DT release increased with increasing PVP content and drug/polymer ratio (d/p) of the blend microspheres. The highest DT release percentage was obtained as 99% for PVP/NaAlg ratio of 1/2 with d/p ratio of 1/2 at the end of 4 h. It was also observed from release results that DT delivery from the microspheres through the external medium are much higher at low pH (1.2) value than that of high pH (6.8) value. The drug release from the microspheres mostly followed Fickian transport. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Study of electrospinning of sodium alginate,blended solutions of sodium alginate/poly(vinyl alcohol) and sodium alginate/poly(ethylene oxide)

Alginate is an interesting natural biopolymer for many of its merits and good biological properties. This paper investigates the electrospinning of sodium alginate (NaAlg), NaAlg/PVA‐ and NaAlg/PEO‐ blended systems. It was found in this research that although NaAlg can easily be dissolved in water, the aqueous NaAlg solution could not be electrospun into ultrafine nanofibers. To overcome the poor electrospinnability of NaAlg solution, synthetic polymers such as PEO and PVA solutions were blended with NaAlg solution to improve its spinnability. The SEM images of electrospun nanofibers showed that the alginate (2%, w/v)–PVA (8%, w/v) blended system in the volume ratio of 70 : 30 and the alginate (2%, w/v)–PEO (8% w/v) blended system in the volume ratio of 50 : 50 could be electrospun into finest and uniform nanofibers with average diameters of 118.3 nm (diameter distribution, 75.8–204 nm) and 99.1 nm (diameter distribution, 71–122 nm), respectively. Rheological studies showed a strong dependence of spinnability and fiber morphology on solution viscosity and thus on the alginate‐to‐synthetic polymer (PVA or PEO) blend ratios. FTIR studies indicate that there are the hydrogen bonding interactions due to the ether oxygen of PEO (or the hydroxyl groups of PVA) and the hydroxyl groups of NaAlg. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Temperature sensitive semi‐IPN microspheres from sodium alginate and N‐isopropylacrylamide for controlled release of 5‐fluorouracil

Semi‐interpenetrating network (IPN) of sodium alginate (NaAlg) and N‐isopropylacrylamide (NIPAAm) microspheres were prepared by water‐in‐oil (w/o) emulsification method. The microspheres were encapsulated with 5‐fluorouracil (5‐FU) and release patterns carried in 7.4 pH at temperatures of 25 and 37°C. The semi‐IPN microspheres were characterized by Fourier transform infrared spectroscopy (FTIR). Differential scanning calorimetry (DSC) and scanning electron microscopic studies were done on the drug‐loaded microspheres to confirm the polymorphism of 5‐FU and surface morphology of microspheres. These results indicated the molecular level dispersion of 5‐FU in the semi‐IPN microspheres. Particle size and size distribution were studied by laser light diffraction technique. Microspheres exhibited release of 5‐FU up to 12 h. The swelling studies were carried in 1.2 and 7.4 pH buffer media at 25 and 37°C. Drug release from NaAlg‐NIPAAm semi‐IPN microspheres at 25 and 37°C confirmed the thermosensitive nature by in vitro dissolution. The micro domains have released in a controlled manner due the presence of NIPAAm in the matrix. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Novel methyl cellulose‐grafted‐acrylamide/gelatin microspheres for controlled release of nifedipine

Naturally available carbohydrate polymers such as methylcellulose (MC) and gelatin (Ge) have been widely studied in the previous literature for controlled release (CR) applications. In this study, methyl cellulose‐g‐acrylamide/gelatin (MC‐g‐AAm/Ge) microspheres were prepared by water‐in‐oil (W/O) emulsion method and crosslinked with glutaraldehyde to encapsulate with nifedipine (NFD), an antihypertensive drug. The microspheres prepared were characterized by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and laser particle size analyzer. DSC thermograms of NFD‐loaded AAm‐MC/Gel microspheres confirmed the molecular level distribution of NFD in the matrix. SEM indicated the formation of spherical particles. Swelling experiments supported the drug diffusion characteristics and release data of the matrices. Cumulative release data were analyzed using an empirical equation to understand the nature of transport of drug through the matrices. Controlled release characteristics of the matrices for NFD were investigated in pH 7.4 media. Drug was released in a controlled manner up to 12 h. Particle size and size distribution of the microspheres as studied by laser light diffraction particle size analyzer indicated their sizes to be around 120 μm. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Preparation,characterization, and salicylic acid release behavior of chitosan/poly(vinyl alcohol) blend microspheres

Blend microspheres of chitosan (CS) with poly(vinyl alcohol) (PVA) were prepared as candidates for oral delivery system. CS/PVA microspheres containing salicylic acid (SA), as a model drug, were obtained using the coacervation‐phase separation method, induced by addition of a nonsolvent (sodium hydroxide solution) and then crosslinked with glutaraldehyde (GA) as a crosslinking agent. The microspheres were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy. Percentage entrapment efficiency, particle size, and equilibrium swelling degree of the microsphere formulations were determined. The results indicated that these parameters were changed by preparation conditions of the microspheres. Effects of variables such as CS/PVA ratio, pH, crosslinker concentration, and drug/polymer (d/p) ratio on the release of SA were studied at three different pH values (1.2, 6.8, and 7.4) at 37°C. It was observed that SA release from the microspheres increased with decreasing CS/PVA ratio and d/p ratio whereas it decreased with the increase in the extent of crosslinking. It may also be noted that drug release was much higher at pH 1.2 than that of at pH 6.8 and 7.4. The highest SA release percentage was obtained as 100% for the microspheres prepared with PVA/CS ratio of 1/2, d/p ratio of 1/2, exposure time to GA of 5 min, and concentration of GA 1.5% at the end of 6 h. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Development of tunable biodegradable polyhydroxyalkanoates microspheres for controlled delivery of tetracycline for treating periodontal disease

This article was aimed at preparation and characterization of drug delivery carriers made from biodegradable polyhydroxyalkanoates (PHAs) for slow release of tetracycline (TC) for periodontal treatment. Four PHA variants; polyhydroxybutyrate (PHB), poly(hydroxybutyrate‐co‐hydroxyvalerate) with 5, 12, and 50% hydroxyvalerate were used to formulate TC‐loaded PHA microspheres by double emulsion‐solvent evaporation method. We also compared the effect of different molecular weight (M_w) of polyvinyl alcohol (PVA) acting as surface stabilizer on particle size, drug loading, encapsulation efficiency, and drug release profile. The TC‐loaded PHA microspheres exhibited microscale and nanoscale spherical morphology under scanning electron microscopy. Among formulations, TC‐loaded PHB:low M_w PVA demonstrated the highest TC loading with slow release behavior. Our results showed that the release rate from PHA microspheres was influenced by both the type of PHA and M_w of PVA stabilizer. Lastly, TC‐loaded PHB microspheres showed efficient killing activity against periodontitis‐causing bacteria, suggesting its potential application for treating periodontal disease. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44128.     

Fabrication and characterization of colon specific eudragit coated graphene oxide microsphere for sustained delivery of tramadol hydrochloride

ABSTRACT

Present investigation reports a straight forward method for synthesis of graphene oxide (GO) followed by fabrication of graphene oxide microsphere (GMS) using water in oil (w/o) emulsification technique. For colon specific drug delivery, enteric coating is desirable, which was done using Eudragit S100 and characterized by Fourier transform Infrared Spectroscopy (FTIR). The surface morphology of fabricated microsphere was confirmed using scanning electron microscopy (SEM). Drug loaded microspheres demonstrated a high payload capacity for model drug tramadol hydrochloride (TmH). The comparative In-vitro drug release showed around 72.37% release from uncoated microspheres, whereas eudragit coated microspheres retarded the drug release upto 10 h.     

井冈霉素载药二氧化硅空心微球的原位制备及缓释性能评价

利用正硅酸乙酯在W/O乳液中的原位水解聚合,成功制备了包埋井冈霉素的二氧化硅载药空心微球. 对所得产品进行了SEM, XRD, FT-IR和粒径分布等分析,结果表明,载药空心微球粒径分布窄,范围在7.5~15 mm,球状形貌良好,具有空心结构,呈无定型态. 热重分析表明载药空心微球的药物负载量约为31.9%(w),缓释溶出实验显示载药空心微球药物释放持续时间约240 min,最终释放量达总载药量的90%以上.     

Preparation and characterization of PVA films with magnetic nanoparticles: The effect of particle loading on drug release behavior

This article deals with the drug release behavior of theophylline (Th) from poly(vinyl alcohol) (PVA) hydrogels, prepared with magnetic nanoparticles at different particle loadings. These biocompatible matrices were obtained by incorporating different amounts of an aqueous ferrofluid into PVA hydrogels, loaded with Th as a marker for drug‐delivery studies. PVA films with magnetic particles proved to be magnetic field‐responsive materials as the drug release decreased through the application of a relative low and uniform magnetic field for particle concentrations of 0.9% w/w or higher. Moreover, the percentage of restriction of drug release is found to be correlated with particle loading. The in vitro release profiles were analyzed by applying a semiempirical power law to obtain the kinetic parameters. The value of the release exponent was found to be in the range 0.54–0.56 in all experiments, which thus indicates a predominant diffusional mechanism for drug release from these smart magnetic hydrogels. This effect suggests the possibility of modulating the release behavior by controlling the particle content in the preparation of the composites. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

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     

海藻酸钙/埃洛石载药微球的制备与缓释盐酸二甲双胍性能

缓释可提高药物利用率,降低其毒副作用。采用交联法制备了海藻酸钙/埃洛石载药微球,以载药微球对盐酸二甲双胍（MH）药物的包封率和缓释效果为考察对象,研究了载药微球的制备工艺和缓释性能,并通过SEM、FTIR和TGA对其结构进行了表征。结果表明：在交联温度为0℃、海藻酸钠用量为1g、埃洛石添加量为2g时,能得到较优的载药微球包封率（79.23%）。上述条件下制得的复合载药微球在pH=6.8的磷酸盐缓冲液中能有效缓释,且720min后缓释度可达85.83%,说明其具有较好的pH敏感性和缓释效果。SEM表明海藻酸钙颗粒与埃洛石在载药微球内部形成复合结构,FTIR表明MH主要以物理包埋的形式于载药微球中,TGA表明添加埃洛石可以提高复合材料在200℃以上的热稳定性。     

PLA Microspheres-Embedded PVA Hydrogels Prepared by Gamma-Irradiation and Freeze-Thaw Methods as Drug Release Carriers

A drug delivery system based on poly (vinyl alcohol) (PVA) hydrogels containing ibuprofen-loaded poly (lactic acid) (PLA) microspheres was developed to improve the release kinetics of this model drug. Gamma-irradiation and freeze-thawing were applied to prepare poly (vinyl alcohol) hydrogels. Properties and morphology of these composite hydrogels were investigated using FTIR, DSC, and SEM. In vitro release indicated that entrapment of the microspheres into the PVA hydrogels causes a reduction in both the release rate and the initial burst effect. PLA microspheres entrapped into the PVA hydrogels showed more suitable controlled release kinetics for drug delivery.     

Preparation and evaluation of poly(3‐hydroxybutyrate) microspheres containing bovine serum albumin for controlled release

The utility of the Poly(3‐hydroxybutyrate) (PHB) to encapsulate and control the release of bovine serum albumin (BSA), via microspheres, was investigated. Various preparing parameters, including polymer concentration in oil phase, emulsification concentration in external water phase, volume ratio of inner water phase to oil phase, and volume ratio of primary emulsion to external water phase were altered during the microspheres production. The effects of these changes on the morphological characteristics of the microspheres, size of the microspheres, drug loading, encapsulation efficiency, and drug release rates were examined. The diameter of the microspheres ranged from 6.9 to 20.3 μm and showed different degrees of porous structure depending on the different preparation parameters. The maximum and minimum BSA encapsulation efficiency within the polymeric microspheres were 69.8 and 7.5%, respectively, varying with preparation conditions. The controlled release characteristics of the microspheres for BSA were investigated in pH 7.4 media. The initial BSA burst release from 8.9 to 63.1% followed by constant slow release for 28 days was observed for BSA from BSA‐loaded microspheres and followed the Higuchi matrix model. So, the release behavior of microspheres showed the feasibility of BSA‐loaded microspheres as controlled release devices. Pristine BSA, pristine PHB microspheres, and BSA‐loaded microspheres were analyzed by Fourier transform infrared spectrophotometer, which indicated no interaction between BSA and PHB. Differential scanning calorimetry on BSA‐loaded microspheres indicated a molecular level dispersion of BSA in the microspheres. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Novel blend microspheres of poly(vinyl alcohol) and succinyl chitosan for controlled release of nifedipine

Water-soluble succinyl chitosan (SCS) was synthesized by reacting succinic anhydride with –OH and –NH₂ reactive groups of chitosan (CS). The blend hydrogel microspheres were prepared from SCS with poly(vinyl alcohol) (PVA) by water-in-oil (w/o) emulsion cross-linking using glutaraldehyde (GA) as the cross-linking agent. Nifedipine (NFD), an antihypertensive drug having a plasma half-life of 2 h, was encapsulated giving encapsulation efficiency up to 92 % and its release was extended up to 12 h. Scanning electron microscopy (SEM) confirmed the spherical nature and smooth surfaces of the microspheres, while Fourier transform infrared spectroscopy (FTIR) confirmed succinylation of CS and chemical stability of NFD in the matrix. Thermogravimetry (TGA) and differential scanning calorimetry (DSC) characterized the SCS and the blend hydrogel microspheres. X-ray diffraction (XRD) and DSC were also used to study the crystalline or amorphous nature of NFD. Swelling and in vitro release experiments performed in pH 1.2 and 7.4 buffer media showed a dependence of blend composition, extent of cross-linking and pH of the media. The mechanism of drug release as analyzed by an empirical equation, suggested non-Fickian trends.     

Biodegradable poly(sebacic acid‐co‐ricinoleic‐ester anhydride) tamoxifen citrate implants: Preparation and in vitro characterization

The aim of this study was to prepare tamoxifen citrate loaded cylindrical polymeric implants for application at tumor sites. The implant was based on poly (sebacic acid‐co‐ricinoleic‐ester anhydride) 70 : 30 w/w [poly(SA‐RA) 70 : 30 w/w], a low‐melting, biodegradable, and biocompatible polymer. Implants were prepared by a standardized melt manufacturing method. Differential scanning calorimetry and scanning electron microscopy were used for implant characterization. In vitro drug release studies were performed in phosphate‐buffered saline (pH 7.4) at 37 ± 2°C. The drug content was estimated by high‐performance liquid chromatography. The differential scanning calorimetry studies showed that the tamoxifen citrate in the implants was in the amorphous state. The cumulative percentage of drug release from 10 and 20 wt % drug‐loaded poly(SA‐RA) 70 : 30 w/w implants after 30 days was found to be 42.36 and 62.60%, respectively. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Development of polylactide microspheres for protein encapsulation and delivery

The development of injectable microparticles for protein delivery is a major challenge. We demonstrated the possibility of entrapping human serum albumin (HSA) and thrombin (Thr) in poly(ethylene glycol) (PEG)‐coated, monodisperse, biodegradable microspheres with a mean diameter of about 10 μm. In our earlier studies, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) analysis was used to characterize the surface of PEG‐coated, taxol‐loaded poly(lactic acid) (PLA) microspheres. An analysis by DRIFTS revealed that PEG was incorporated well on the PLA microsphere surface. An emulsion of protein (in water) and PLA dissolved in an acetone–dichloromethane (or acetone–chloroform) mixture were poured into an aqueous solution of PEG [or poly(vinyl alcohol) (PVA)] with stirring with a high‐speed homogenizer for the formation of microparticles. HSA recovery in microspheres ranged from 13 to 40%, depending on the solvent and emulsification systems used for the preparation. PLA dissolved in a dichloromethane/acetone system and albumin loaded via a PEG emulsification solution (PLA–PEG–HSA) showed maximum drug recovery (39.5%) and drug content (9.9%). Scanning electron microscopy revealed that PEG‐coated microspheres had less surface micropores than PVA‐based preparations. The drug‐release behavior of microspheres suspended in phosphate‐buffered saline exhibited a biphasic pattern. An initial burst release (30%) followed by a constant slow release for 20 days was observed for HSA and Thr from PLA–PEG microspheres. PEG‐coated PLA microspheres show great potential for protein‐based drug delivery. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1285–1295, 2002