Synthesis and characterization of chitosan‐polycaprolactone blended with organoclay for control release of doxycycline

In the present research program, chitosan has been mixed with polycaprolactone (PCL) (80 : 20) for using them for control delivery of doxycycline. Organoclay, Cloisite 30B of different concentrations 1, 2.5, and 5% has been blended with the composite. Chitosan is a natural biodegradable polymer where as polycaprolactone is a synthetic biopolymer. The blending of the two polymers has been carried out varying the proportion of nanoclay so that the composite can be a better drug carrier. The blends were characterized by Fourier Transmission Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), X‐ray Diffraction (XRD) analysis. From the FTIR spectra, the various groups present in chitosan and PCL blend were monitored. The homogeneity, morphology, and crystallinity of the blends were ascertained from SEM and XRD data, respectively. The swelling studies have been carried out at different drug loading. Swelling study is an important parameter to predict the diffusion of the drugs from the matrix. The kinetics of the drug delivery system has been systematically studied. Drug release kinetics was analyzed by plotting the cumulative release data versus time by fitting to an exponential equation which indicated the non‐Fickian type of kinetics. The drug release was investigated at different pH medium, and it was found that the drug release depends upon the pH medium as well as the nature of matrix. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Effects of drying process for amorphous waxy maize starch on theophylline release from starch‐based tablets

Physical properties and theophylline‐release profiles of compressed tablets prepared with amorphous waxy maize starches dried using different methods were examined. A gelatinized waxy maize starch paste (10% solids in water) was either freeze‐dried or oven‐dried (40 or 105°C) until the moisture content reached to <5%. To form the tablets, the dried amorphous starch powders, either with or without theophylline (3 : 10, w/w), were remoistened to a water content of (17 ± 0.2)%, and compressed into tablets. The drying process applied to the amorphous starch powders affected both the compactness and swelling behavior of the tablets. Although no crystallinity was detected in all the starches tested, X‐ray diffraction patterns indicated that starch chains dried at the lower temperature (40°C) are allowed more time to re‐associate during the drying process than those dried at the higher temperature (105°C). The freeze‐dried starch powders formed tablets characterized by greater compactness and rigidity than was observed in the oven‐dried starch samples. The drug release of the tablets prepared with the starch dried at the higher temperature (105°C) occurred at a much slower rate than that of the tablets made with the starch dried at the lower temperature (40°C). The drug release characteristics of the freeze‐dried starch tablets were nearly identical to those of the tablets prepared with the starch dried at 105°C. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Ethyl methacrylate grafted on two starches as polymeric matrices for drug delivery

The use of copolymers grafted on starch for controlled‐release technology is an interesting proposal, since a modification of a natural polymer is more suitable than synthetic polymers because of its biocompatibility and biodegradability. The aim of this paper is to synthesize acrylic polymers grafted on carbohydrates to investigate the release kinetic of different solubility drugs from polymeric matrix systems and to observe the effect of grafted copolymers and drug solubility on the release mechanism. Copolymer variables such as carbohydrate content, stereoregularity of grafted chains, particle size, morphology, sensitivity to hydration, and rheological properties are discussed. Tablets were prepared by direct compression of the graft copolymer and drug. The drugs' release in vitro kinetics was studied by dissolution testing. Drug release from tablets depends on polymer matrix, polymer content, drug, and pH. An increase in drug solubility results in an increase in the rate of dissolution, as in the case of a poor hydrophilic matrix. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 523–536, 2005     

Preparation of poly(ethylene glycol)/chitosan membranes by a glucose‐mediating process and in vitro drug release

Novel pH‐dependent chitosan/poly(ethylene glycol) (PEG) membranes were developed for oral drug delivery. The preparation of these membranes involved a solution‐mediating process with glucose addition at different pHs. Fourier transform infrared/attenuated total reflectance showed that the Schiff‐base reaction was favored at high pHs and high glucose concentrations. X‐ray diffraction analysis showed a continuous increase in the glucose addition transformed the chitosan/PEG samples into amorphous polymers. The equilibrium swelling measurements showed that the swelling ratio of the solution‐mediated membranes decreased as the glucose concentration increased, and this was demonstrated by degree‐of‐mediation analysis. The glucose‐mediated membranes had different degrees of mediation, which depended on the pH and glucose concentration. The in vitro release profiles of theophylline‐loaded, pH 6 treated, glucose‐mediated membranes showed that the theophylline release decreased as the glucose concentration increased. Also, the release behavior of the theophylline from the glucose‐mediated membranes varied with the pH of the release medium, the glucose concentration, and the final pH of the glucose‐mediated chitosan/PEG gels. Chitosan/PEG membranes prepared by a basic glucose‐mediated process could lead to successful applications in localized drug delivery to the intestine. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1083–1094, 2005     

Kinetics of drug release from drug carrier of polymer/TiO2 nanotubes composite—pH dependent study

This study was to investigate the kinetics of drug release from polymer/TiO₂ nanotubes composite. Lidocaine and carprofen were selected as model drugs to represent weak base and weak acid drugs, respectively. Mathematical models used to fit the in vitro drug release experimental data indicate that at higher pH, the drug release was first order diffusion controlled. At lower pH, the release of the two drugs exhibits two staged controlled release mechanism. The first phase is due to drug diffusion and the second stage is a result of poly(lactic‐co‐glycolic acid) (PLGA) polymer degradation. The rate of drug release from polymer/TiO₂ nanotubes drug carrier was mainly controlled by three pH dependent factors: the solubility of the drug, the degree of polymer swelling/degradation, and the electrostatic force between polymer and drug. This study suggests that controlled release could be achieved for polymer/TiO₂ nanotubes drug carrier via the modulation of pK_a values of polymers and drug solubility. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41570.     

甲硝唑缓释片制备与药物释放

利用湿法造粒,制备了甲硝唑羟丙基甲基纤维素(HPMC)骨架缓释片。实验结果表明,提高HPMC质量分数与使用高粘度HPMC可有效降低释药速率,但粘度4 000 mPa.s以上HPMC释药速率的降低不明显;含有粒径较大的甲硝唑原药的片剂,由于药物较强的致孔作用,药物释放速率较高;由于表面积较小的键形片上,HPMC水化凝胶层面积相对较小,甲硝唑从键形片的释放快于表面积较大的圆形片的释放。HPMC粘度、药物颗粒粒径与片形对释药速率的影响都与药物的溶解度有关。机制分析表明,药物曲线的释放符合H iguch i方程。     

γ‐Irradiation preparation of poly(acrylic acid)–chitosan hydrogels for in vitro drug release

Biocompatible and biodegradable pH‐responsive hydrogels based on poly(acrylic acid) and chitosan were prepared for controlled drug delivery. These interpolymeric hydrogels were synthesized by a γ‐irradiation polymerization technique. The degree of gelation was over 96% and increased as the chitosan or acrylic acid (AAc) content increased. The equilibrium swelling studies of hydrogels prepared under various conditions were carried out in an aqueous solution, and the pH sensitivity in a range of pH 1–12 was investigated. The AAc/chitosan hydrogels showed the highest water content when 30 vol % AAc and 0.1 wt % chitosan were irradiated with a 30 kGy dose of radiation. In addition, an increase of the degree of swelling with an increase in the pH was noticed and it had the highest value at pH 12. The drug 5‐fluorouracil was loaded into these hydrogels and the release studies were carried out in simulated gastric and intestinal fluids. The in vitro release profiles of the drugs showed that more than 90% of the loaded drugs were released in the first 1 h at intestinal pH and the rest of the drug was released slowly. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3270–3277, 2003     

Preparation and Characterization of Carboxymethyl Chitosan and β-Cyclodextrin Microspheres by Spray Drying

Three kinds of carboxymethyl chitosan/β-cyclodextrin microspheres loaded with theophylline were prepared by spray drying intended for pulmonary delivery. Mucociliotoxicity, permeation rate, and drug release characteristics of the product were investigated. The microspheres obtained by spray drying were found to be spherical with smooth or wrinkled surfaces. The mean particle size was between 3.39 and 6.06 µm. The microspheres demonstrated high product yield (43.7-50.2%), high drug loading (13.7-38.1%), and high encapsulation efficiency (86.9-92.8%). FT-IR indicated that there were interactions of theophylline with carboxymethyl chitosan matrix. Further studies on mucociliotoxicity and permeation confirmed that microspheres had better adaptability and high permeation rate. In vitro drug release from the microspheres was not related to the drug/polymer ratios.     

Swelling and drug‐release behavior of the poly(AA‐co‐N‐vinyl pyrrolidone)/chitosan interpenetrating polymer network hydrogels

A series of novel hydrogels were prepared from acrylic acid (AA), N‐vinyl pyrrolidone (NVP), and chitosan by photopolymerization. The swelling behavior, gel strength, and drug release behavior of the poly(AA/NVP) copolymeric hydrogels and corresponding interpenetrating polymer network hydrogels were investigated. Results showed that the swelling ratios for the present hydrogels decreased with an increase of NVP content in the gel, but the gel strength increased with an increase of NVP content in the gel. Results also showed that the drug‐release behavior for the gels is related to the ionicity of drug and the swelling ratio of the gel. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 2135–2142, 2004     

pH‐sensitive alginate/soy protein microspheres as drug transporter

The complex microspheres based on alginate (AL) and soy protein isolate (SPI) were prepared by solution blending and then Ca²⁺ crosslinking, and their function as drug carrier was explored as well. The effects of composition on the structures of microspheres were studied, and the XRD results proved the miscibility between components. Meanwhile, FTIR results suggested that such miscibility was driven by strong hydrogen bonding. Especially, the complex microsphere with equal content of AL and SPI had the best miscibility by morphological analysis, shown as a smooth and uniform surface of SEM images. The controlled release function of the complex microspheres was verified using theophylline as a drug model, that is, the swelling and drug release were affected by pH conditions and showed obvious differences under given pH of stomach, intestine, and colon. Moreover, the intestine and colon may be optimal site for prompt release of drugs. Except for the attribution of AL component to pH sensitivity, the complex microspheres also inherited the bioactivity of SPI component, which may lower irritants of drug to the tissues in body. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Preparation of poly(acrylic acid)–chitosan hydrogels by gamma irradiation and in vitro drug release

Biocompatible and biodegradable pH‐responsive hydrogels based on poly(acrylic acid) (AAc) and chitosan were prepared for controlled drug delivery. These interpolymeric hydrogels were synthesized by a gamma irradiation polymerization technique. The degree of gelation was over 96% and increased as the chitosan or acrylic acid content increased. The equilibrium swelling studies of hydrogels prepared in various conditions were carried out in an aqueous solution, and the pH sensitivity in the range of pH 1–12 was investigated. The AAc/chitosan hydrogels showed the highest water content when the 30 vol % AAc and 0.1 wt % chitosan were irradiated with a 30‐kGy radiation dose. Also, an increase of swelling degree with an increase in the pH was noticed and showed the highest value at pH 12. The drug, 5‐fluorouracil, was loaded into these hydrogels and the release studies were carried out in simulated gastric and intestinal fluids. The in vitro release profiles of the drugs showed that more than 90% of the loaded drugs were released in the first 1 h at the intestinal pH and the rest of the drug had been released slowly. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3660–3667, 2003     

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     

Preparation and Characterization of Carboxymethyl Chitosan and β-Cyclodextrin Microspheres by Spray Drying

Three kinds of carboxymethyl chitosan/β-cyclodextrin microspheres loaded with theophylline were prepared by spray drying intended for pulmonary delivery. Mucociliotoxicity, permeation rate, and drug release characteristics of the product were investigated. The microspheres obtained by spray drying were found to be spherical with smooth or wrinkled surfaces. The mean particle size was between 3.39 and 6.06 µm. The microspheres demonstrated high product yield (43.7–50.2%), high drug loading (13.7–38.1%), and high encapsulation efficiency (86.9–92.8%). FT-IR indicated that there were interactions of theophylline with carboxymethyl chitosan matrix. Further studies on mucociliotoxicity and permeation confirmed that microspheres had better adaptability and high permeation rate. In vitro drug release from the microspheres was not related to the drug/polymer ratios.     

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     

Chitosan–Polyelectrolyte complexation for the preparation of gel beads and controlled release of anticancer drug. I. Effect of phosphorous polyelectrolyte complex and enzymatic hydrolysis of polymer

Enzymic hydrolyzed chitosan was employed to prepare chitosan–tripolyphosphate and chitosan–polyphosphoric acid gel beads using a polyelectrolyte complexation method for the sustained‐release of anticancer agent, 6‐mercaptopurine (6‐MP). pH responsive swelling ability, drug‐release characteristics, and morphology of the chitosan gel bead depends on polyelectrolyte complexation mechanism and molecular weight of the enzymic hydrolyzed chitosan. The complexation mechanism of chitosan beads gelled in pentasodium tripolyphosphate or polyphosphoric acid solution was ionotropic crosslinking or interpolymer complex, respectively. The drug‐release patterns of all chitosan gel beads in pH 6.8 seemed to be diffusional based, which might be in accordance with the Higuchi model, whereas release profiles of the chitosan–tripolyphosphate gel beads in pH 1.2 medium seemed to be non‐Fickian diffusion controlled due to the swelling or matrix erosion of the beads. The rate of 6‐MP releasing from chitosan–tripolyphosphate or chitosan–polyphosphoric acid gel matrix were significantly increased with the decreased molecular weight of enzymic hydrolyzed chitosan. However, the dissolution rates of 6‐MP entraped in chitosan–tripolyphosphate and chitosan–polyphosphoric acid gel matrix were significantly slower than the dissolution rate of the original drug. These results indicate that the chitosan–polyphosphoric acid gel bead is a better polymer carrier for the sustained release of anticancer drugs in simulated intestinal and gastric juice medium than the chitosan–tripolyphosphate gel beads. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 1868–1879, 1999     

壳聚糖-琼胶复合微球的制备及其药物释放性能

采用小分子离子交联法制备了pH值敏感的壳聚糖-琼胶复合微球,对壳聚糖-琼胶复合微球的粒径、形貌、pH值敏感性等进行了表征.以茶碱为模型药物研究了壳聚糖-琼胶复合微球的药物释放性能,结果发现一定量琼胶的引入有助于改善壳聚糖微球的药物缓释性能.     

Synthesis and characterization of chitosan/cloisite 30B film for controlled release of ofloxacin

In this research program, chitosan film was prepared by blending chitosan with Cloisite 30 B at different concentrations 0 wt %, 1 wt %, and 2.5 wt %. The blends were characterized by Fourier transmission infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X‐ray diffraction (XRD) analysis. From the FTIR spectra the various groups present in chitosan/C 30 B blend were monitored. The homogeneity, morphology, and crystallinity of the blends were ascertained from SEM and XRD data, respectively. The most suitable form of blend was taken and used as a carrier for the controlled release of ofloxacin. The swelling studies have been carried out at different drug loading. Drug release kinetics was analyzed by plotting the cumulative release data versus time by fitting to an exponential equation which indicated the occurrence of non‐Fickian type of kinetics. The drug release was investigated at different pH medium and it was found that the drug release depends upon the pH medium as well as the nature of matrix. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

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     

Hydrogels from scleroglucan and ionic crosslinkers: Characterization and drug delivery

The polysaccharide scleroglucan (Sclg), exploited as a matrix suitable for modified drug delivery, was crosslinked in the presence of three ions: borate, aluminum, and iron. A rheological investigation indicated the main differences between the hydrogels in their viscoelastic linear response: the Sclg/borax system showed the highest strength when deformed by elongation, whereas the strength of the other systems broke down, in terms of viscosity, at much lower values of the imposed strain. Tablets prepared from the gels showed remarkable differences in their water uptake and dimensional swelling. On the other hand, the tablets, loaded with drugs of different steric hindrances, showed similar release behavior, regardless of the crosslinking agent. Scanning electron microscopy analysis was related to the delivery and rheological profiles. Texture analysis, carried out on tablets swollen for 5 h, showed different values of cohesion. Furthermore, when the generalized Maxwell model was applied to the relaxation data, the obtained mechanical spectra showed a more pronounced solidlike character of the Sclg/iron network in comparison with the prevailing viscous behavior of the other matrices. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Solute transport in poly(2-hydroxyethyl methacrylate) hydrogel membranes

The swelling, permeation, and release characteristics for benzoic acid, caffeine, propranolol hydrochloride, and diclofenac sodium in crosslinked poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels were examined. Increasing polymer crosslinking density resulted in decreases in the degree of swelling, drug loading, the diffusivity of solute in the hydrogels, and in the rate of drug release. Diclofenac sodium led to an abnormally large degree of swelling as the maximum value is given as 6.5, while the highest for the other three was 1.07. That the logarithmic drug diffusivity was proportional to the reciprocal of hydration indicates that the free volume theory accounts for the transport of solute in the gels. Increasing the concentration resulted in increases in the diffusivities, solubilities, and permeabilities of the solutes in the hydrogels. The drug release kinetics from most wet hydrogel samples can be well-fitted by a Fickian diffusion model. Near zero-order release is observed only for dry samples with caffeine of low loading.