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In this report, novel pH-sensitive interpenetrated network (IPN) polyspheres were developed utilizing polyacrylamide-g-locust bean gum (PAAm-g-LBG) in combination with sodium alginate (SA) to achieve intestinal targeted delivery of ketoprofen. PAAm-g-LBG was synthesized under microwave irradiation wherein ceric ammonium nitrate was used as reaction initiator and then conversion of PAAm-g-LBG as pH-sensitive copolymer was carried out by alkaline hydrolysis. The PAAm-g-LBG copolymer was characterized through 1H-NMR, FTIR and elemental analysis. The IPN polyspheres exhibited pH-depended swelling or de-swelling with the alteration of surrounding pH. The in-vitro release of drug from IPN polyspheres was found to be higher (≈ 90%) in phosphate buffer of pH 7.4 in comparison with that in pH 1.2 buffer (10.6%). The in-vivo pharmacokinetic, anti-inflammatory screening and stomach histopathology studies performed on Wistar rats revealed pH sensitivity of IPN polyspheres where ketoprofen was successfully targeted to small intestine resulting in reduced side effects of ketoprofen like ulcer formation, erosion of gastric mucosa and hemorrhages.

This study was undertaken to investigate correlation between the carboxymethylation-induced rheological changes and drug release characteristics of locust bean gum (LBG) matrix tablets. LBG was derivatized to carboxymethyl LBG (CMLBG) and characterized by (13)C NMR, FTIR and elemental analyses. Rheological studies revealed that LBG, in contact with water, produced a strong elastic gel which swelled less due to lower penetration of water resulting in slower drug release. On the other hand, CMLBG formed a viscous polymer solution through which higher influx of water resulted in rapid swelling of the matrix and faster drug release. Although the release from a particular matrix was dependent on drugs' solubilities, CMLBG matrix tablet produced faster release of all the drugs than LBG matrix tablets. In conclusion, rheological study appeared to be an useful tool to predict release of drugs from polysaccharide matrix tablets.

This article reports the development of pH-sensitive interpenetrating polymer network (IPN) microbeads using polyacrylamide-grafted-gum ghatti (PAAm-g-GG) and sodium alginate (SA) for gastro-protective controlled delivery of ketoprofen. We have synthesized PAAm-grafted-GG copolymer under microwave irradiation using cerric ammonium nitrate as reaction initiator; further, the PAAm-g-GG was converted to pH-sensitive copolymer through alkaline hydrolysis. Sophisticated instrumentation techniques were used to characterize PAAm-g-GG. The IPN microbeads of PAAm-g-GG and SA, pre-loaded with ketoprofen were prepared by dual crosslinking using Ca2+ ions and glutaraldehyde (GA). The IPN microbeads demonstrated excellent pH-sensitive behavior as noted in the pulsatile swelling test and scanning electron microscopy. IPN microbeads also showed larger amount of drug release in buffer solution of pH 7.4 as compared to drug release in solution of pH 1.2. The in vivo pharmacokinetic, pharmacodynamic and stomach histopathology studies conducted on wistar rats confirmed the pH-sensitive controlled release of ketoprofen; IPN microbeads retarded the drug release in stomach resulting in reduced adverse effects of ketoprofen.

The purpose of this work was to evaluate different methods of cross-linking for developing diltiazem–resin complex loaded carboxymethyl xanthan gum (CMXG) hydrogel beads to achieve highest possible drug entrapment and extended release for effective cardio-protection. The hydrogel beads were prepared by ionic cross-linking and dual cross-linking using simultaneous (SIM) and sequential (SEQ) methods. Among the three methods, SEQ method produced smaller sized beads having higher drug entrapment efficacy and prolonged release characteristics as evidenced from mean dissolution time and diffusion coefficient of drug. Keeping the concentration of ionic cross-linker constant, increase in the amount of covalent cross-linker and cross-linking time decreased the drug release. Higher release of the drug in acid solution was attributed to the higher solubility of the basic drug and higher swelling of the matrices in acid solution. Comparison of FTIR spectra, drug content and dissolution profiles indicated that the drug was stable in the beads when kept under stress condition up to 3 months. In conclusion, the sequential method was found superior for producing CMXG hydrogel beads as a prolonged release delivery device in cardiovascular diseases.

Local drug delivery systems to bone have attracted appreciable attention due to their efficacy to improve drug delivery, healing and regeneration. In this paper, development and characterization of new formulations of bioactive glass into a porous scaffold has been reported for its suitability to act as a drug delivery system in the management of bone infections, in vitro. Two new glass compositions based on SiO 2 –Na 2 O–ZnO–CaO–MgO–P 2 O 5 system (BGZ and MBG) have been developed which after thorough chemical and phase evaluation, studied for acellular static in vitro bioactivity in SBF. Porous scaffolds made of these glasses have been fabricated and characterized thoroughly for bioactivity study, SEM, XRD, in vitro cytotoxicity, MTT assay and wound healing assay using human osteocarcoma cells. Finally, gatifloxacin was loaded into the porous scaffold by vacuum infiltration method and in vitro drug release kinetics have been studied with varying parameters including dissolution medium (PBS and SBF) and with/without impregnation chitosan. Suitable model has also been proposed for the kinetics. 63–66% porous and 5–50 μm almost unimodal porous MBG and BGZ bioactive glass scaffolds were capable of releasing drugs successfully for 43 days at concentrations to treat orthopedic infections. In addition, it was also observed that the release of drug followed Peppas–Korsmeyer release pattern based on Fickian diffusion, while 0.5–1% chitosan coating on the scaffolds decreased the burst release and overall release of drug. The results also indicated that MBG based scaffolds were bioactive, biocompatible, noncytotoxic and exhibited excellent wound healing potential while BGZ was mildly cytotoxic with moderate wound healing potential. These results strongly suggest that MBG scaffolds appear to be a suitable bone drug delivery system in orthopedic infections treatment and as bone void fillers, but BGZ should be handled with caution or studied elaborately in detail further to ascertain and confirm the cytotoxic nature and wound healing potential of this glass.

Silica xerogel and its PEG assisted derivatives were prepared by sol–gel method for controlled release of andrographolide. In vitro and in vivo release of andrographolide from the nano porous silica as well as PEG modified silica matrix were studied. Drug release from the matrix increased with increasing percentage of PEG and followed a biphasic pattern. The in vitro release profile followed zero order kinetics with erosion of the matrix for the first six hours and higuchi model with the diffusion mechanism for rest of the time period. Pharmacokinetic data revealed sustained release of the drug from silica–drug composite with higher elimination t1/2 than the pure drug. For all the formulations Level A in vitro-in vivo correlation (IVIVC) was established with (R2) > 0.98. Histology of different organs was carried out following in vivo administration of the drug-carrier composite. The histological examination demonstrated absence of any inflammatory or degenerative response with the formulations. Fourier transform infrared (FTIR) data revealed the coexistence of andrographolide in the silica matrix. Transmission electron microscope (TEM) images also unfold the repose matrix structure in PEG assisted derivatives than the pure matrix. This study discloses that silica gel and PEG assisted derivatives could be used as a biocompatible and sustained release device for andrographolide.

The effect of Ca(2+) ion concentration on swelling, erosion, and drug release mechanism of Ca(2+) ion cross-linked carboxymethyl xanthan gum (Ca-CMXG) matrices was investigated. By adding CaCl2 solution, carboxymethyl xanthan gum (CMXG) was converted into Ca-CMXG matrix, which was evaluated for swelling, erosion and drug release in different dissolution media. The amount of Ca(2+) ion alters the viscosity of gel layer formed around the matrices resulting in decreased water penetration into swollen layer. The changes in amount of Ca(2+) ion considerably influenced the swelling and erosion of the matrix leading to different drug release profiles. The simultaneous swelling and erosion of matrices that were controlled by the degree of cross-linking prejudiced the drug release mechanism. The release data fitted well into the Korsmeyer-Peppas equation and the combined effect of diffusion and erosion described the overall drug transport mechanism.

Herein, an aqueous solution of etherified locust bean polysaccharide (ELBP) containing lamivudine was reticulated in presence of trivalent aluminium (Al 3+ ) ions to nanoscale level (43.82–197.70 nm) by surfactant assisted homogenization-reticulation technique. The variation in aluminium chloride (AlCl 3 ) strength (1.5–3.5% (w/v)) and drug:ELBP weight ratio (0.11–0.43) affected the properties of the nanoreticulations. Regardless of the variables, a maximum of ∼44% drug entrapment efficiency was noted. In simulated intestinal fluid (phosphate buffer solution, pH 7.4), the drug release rate was inversely proportional to the strength of AlCl 3 ; but followed a proportional relationship with the drug:ELBP ratio. The mechanism of drug release shifted from Fickian diffusion to anomalous transport as the salt strength was increased above 2.5% (w/v). At intermediate drug:ELBP ratio, the drug release rate was regulated by polymer chain relaxation as opposed to simple diffusion mechanism. Fourier transform infrared spectroscopy did not show any evidence of chemical interaction between the drug and ELBP. Thermal analysis and X-ray diffraction studies suggested amorphous dispersion of drug in the nanoreticulations. Thus, the nanoreticulations were expected to absorb via intestine and phagocytosed by the virus-infected hepatic macrophages and hence could be useful for controlled delivery of lamivudine avoiding dose-dependent toxicity of the drug.

Considering relatively fast drug release rate of Ca+2/gellan beads in phosphate buffer solution, a novel glipizide-loaded bead system was developed through ionotropic gelation of gellan with trivalent Al+3 ions and covalent cross-linking with glutaraldehyde (GA). Following GA-treatment, spherical Al+3/gellan beads contracted leaving wrinkles on bead surface. A maximum of 97.67% drug entrapment efficiency was achieved; however GA-treatment reduced the same by 11.89%. All the beads released only 10% drug in acidic medium in 2 h; however it was found 38–47% for Al+3/gellan beads and only 15% for GA-treated beads in weakly alkaline medium. The drug release did correlate well with their swelling behaviors. The anomalous drug transport mechanism shifted to super case II transport for GA-treated beads, where the polymer relaxation phenomenon was dominant. The drug was relatively stable, amorphous in the beads. Thus both GA-treated and -untreated Al+3/gellan beads could be useful carriers for the controlled oral delivery of glipizide.

Diltiazem HCl, a water soluble drug was bound to Indion 254®, a cation exchange resin and resulting drug–resin complex was entrapped within interpenetrating polymer network (IPN) microcapsules of gellan gum and egg albumin prepared by ionotropic gelation and covalent crosslinking method. The IPN microcapsules were characterized by SEM, DSC, TGA, XRD and FTIR analyses. The pure drug diltiazem showed rapid and complete dissolution within 60 min, while drug release from drug-resinate was extended for 3 h and that from IPN microcapsules was still slower. The ionically cross-linked microcapsules were capable of releasing drug up to 9 h, and that from dual crosslinked microcapsules was extended up to 15 h. The microcapsules which were prepared with higher concentration of glutaraldehyde released the drug more slowly. The release data were fitted to an empirical equation to determine the transport mechanism.

Interpenetrating network (IPN) matrix tablets of diltiazem-HCl (DTZ) was prepared by wet granulation method using polyacrylamide-grafted-sodium alginate (PAam-g-SAL) co-polymer and sodium alginate (SAL) for sustained release of the drug. Formulation of IPN structure was examined using FTIR spectroscopy, and compatibility of the drug with the polymers was evaluated through FTIR, DSC, and XRD analyses. The effect of co-polymer/SAL ratios, drug load, and total polymer/calcium gluconate (CG) ratios on drug release in acidic and phosphate buffer solutions was investigated. The release of drug was controlled by the relative magnitude of swelling capacity of IPN matrix and viscosity of the gel formed following dissolution of the polymers. The swelling capacity of the matrix was governed by the formation of calcium alginate gel structure and the rigidity imparted by the co-polymer. The results indicated that IPN matrix tablets of PAam-g-SAL and SAL could be used for sustained release of DTZ.