Influence of Ispaghula and Zein Coating on Ibuprofen-Loaded Alginate Beads Prepared by Vibration Technology: Physicochemical Characterization and Release Studies.

The purpose behind the work was to fabricate alginate beads with better drug loading and extended drug release. Ispaghula was used to enhance the drug loading while zein was employed to extend the drug release. Ibuprofen was employed as a model drug in this study. Ibuprofen-loaded alginate beads with and without ispaghula were prepared using vibration technology and coated with zein. The beads prepared with alginate alone were shown to have loading and entrapment efficiencies of 35% and 70% w/w, respectively. Addition of ispaghula in alginate showed a significant increase (p < 0.05) in the drug loading (42% w/w) and entrapment efficiency (84% w/w). Fourier-transform infrared spectroscopy confirmed the presence of ispaghula and zein coating in the alginate beads as well as the ibuprofen loading. Scanning electron microscopy revealed better spherical geometry in the beads with ispaghula. The surface morphology of the uncoated beads was rough due to crystalline and surface drug. The zein coating has produced a smoother surface and particle adhesion. Differential scanning calorimetry has shown a reduction in drug crystallinity. Alginate beads extended the drug release for 4 h and the presence of zein extended the release for 6 h.

Aluminium and radiation cross-linked carboxymethyl sago pulp beads for colon targeted delivery.

The carboxymethyl sago pulp (CMSP) with a degree of substitution of 0.4% was synthesized from sago waste. The CMSP beads with an average diameter of 3.1-4.8 mm were formed by aluminium chloride gelation as well as further cross-linked by irradiation. To evaluate colon targeted release, a model drug, 5-aminosalicylic acid (5-ASA) was encapsulated in CMSP beads. Fourier-transform infrared spectroscopy and X-ray diffraction studies indicated intact and amorphous nature of entrapped drug. A pH dependent drug release was observed, and about 90% of the drug was released only at pH 7.4 over 9 h. Irradiated beads were resisted the drug release in an acidic environment at a higher extent than non-irradiated beads. The drug release from 6% (w/w) of 5-ASA loaded bead followed zero order, whereas, 15 and 22% loaded beads followed first order. The release exponent n value suggests non-fickian transport of 5-ASA from the beads.

Development of gelatin microspheres loaded with diclofenac sodium for intra-articular administration.

We have previously reported on the targeting of diclofenac sodium in joint inflammation using gelatin magnetic microspheres. To overcome complications in the administration of magnetic microspheres and achieve higher targeting efficiency, the present work focuses on the formulation of gelatin microspheres for intra-articular administration. Drug-loaded microspheres were prepared by the emulsification/cross-linking method, characterized by drug loading, size distribution, scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), gas chromatography, and in vitro release studies. The targeting efficiency of microspheres was studied in vivo in rabbits. The microspheres showed drug loading of 9.8, 18.3, and 26.7% w/w with an average size range of 37-46 µm, depending upon the drug-polymer ratio. They were spherical in nature and free from surface drug as evidenced by the SEM photographs. FT-IR, DSC, and XRD revealed the absence of drug-polymer interaction and amorphous nature of entrapped drug. Gas chromatography confirms the absences of residual glutaraldehyde. The formulated microspheres could prolong the drug release up to 30 days in vitro. About 81.2 and 43.7% of administered drug in the microspheres were recovered from the target joint after 1 and 7 days of postintra-articular injection, respectively, revealing good targeting efficiency.

Targeted delivery of diclofenac sodium via gelatin magnetic microspheres formulated for intra-arterial administration.

In the present work, we have attempted to deliver diclofenac sodium to a target site by intra-arterial injection of gelatin magnetic microspheres and subsequent localization using an external magnet. Drug-loaded magnetic microspheres were prepared by emulsification/cross-linking method, characterized by drug loading, magnetite content, size distribution, optical microscopy, scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) analysis, differential scanning calorimetry (DSC), X-ray diffraction (XRD), absence of glutaraldehyde by gas chromatography, and in vitro release studies. The targeting efficiency and the therapeutic efficacy of microspheres were studied in vivo in rabbits. The microspheres showed drug loading of 9.1, 18.7, 24.9% w/w, magnetite content of 27.8-28.9% w/w with an average size range of 25-30.6 mum, depending upon the drug-polymer ratio. They were spherical in nature as evidenced by optical microscopy and SEM. FT-IR, DSC, and XRD studies revealed the absence of drug-polymer interaction. Gas chromatography confirmed the absence of residual glutaraldehyde. The microspheres were able to prolong the drug release over 24-30 days and the application of sonication during in vitro release study has slightly increased the release rate. After intra-arterial administration of microspheres, 77.7% of injected dose was recovered at the target site which revealed good targeting efficiency. The microspheres effectively reduced joint swelling, but lesser extent than the oral diclofenac sodium in high dose, in antigen induced arthritic rabbits without producing gastric ulceration which was observed in rabbits treated with oral diclofenac sodium.

Targeted delivery of diclofenac sodium via gelatin magnetic microspheres formulated for intra-arterial administration.

In the present work, we have attempted to deliver diclofenac sodium to a target site by intra-arterial injection of gelatin magnetic microspheres and subsequent localization using an external magnet. Drug-loaded magnetic microspheres were prepared by emulsification/cross-linking method, characterized by drug loading, magnetite content, size distribution, optical microscopy, scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) analysis, differential scanning calorimetry (DSC), X-ray diffraction (XRD), absence of glutaraldehyde by gas chromatography, and in vitro release studies. The targeting efficiency and the therapeutic efficacy of microspheres were studied in vivo in rabbits. The microspheres showed drug loading of 9.1, 18.7, 24.9 per cent w/w, magnetite content of 27.8-28.9 per cent w/w with an average size range of 25-30.6 mum, depending upon the drug-polymer ratio. They were spherical in nature as evidenced by optical microscopy and SEM. FT-IR, DSC, and XRD studies revealed the absence of drug-polymer interaction. Gas chromatography confirmed the absence of residual glutaraldehyde. The microspheres were able to prolong the drug release over 24-30 days and the application of sonication during in vitro release study has slightly increased the release rate. After intra-arterial administration of microspheres, 77.7 per cent of injected dose was recovered at the target site which revealed good targeting efficiency. The microspheres effectively reduced joint swelling, but lesser extent than the oral diclofenac sodium in high dose, in antigen induced arthritic rabbits without producing gastric ulceration which was observed in rabbits treated with oral diclofenac sodium.

Ultrasonically controlled release and targeted delivery of diclofenac sodium via gelatin magnetic microspheres.

In the present work, an attempt was made to target diclofenac sodium to its site of action through magnetic gelatin microspheres. The gelatin magnetic microspheres loaded with 8.9% w/w of diclofenac sodium and 28.7% w/w of magnetite were formulated by emulsification/cross-linking with glutaraldehyde. The formulated microspheres were characterized by particle size distribution, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction and in vitro release studies. The in vivo distribution and targetability of gelatin magnetic microspheres after i.v. administration were studied in rabbits. The formulated microspheres were below 5 microm and spherical in nature as evidenced by the SEM photographs. DSC and X-ray diffraction studies revealed the absence of drug-polymer interaction. Encapsulated diclofenac sodium was released slowly more than 18 days. Application of sonication, as external stimuli to enhance drug release, during release study, has slightly increased the release rate. The formulated microspheres were injected intravenously after keeping a suitable magnet near the target area. The quantity of drug available at the target and non-target area was determined by HPLC. About 5.5% of injected dose localized near the target organ. Majority of injected dose was recovered from lungs, spleen and liver indicating localization of microspheres in these organs. Further studies are required to improve the targeting efficiency of gelatin microspheres by modifying surface properties to overcome phagocytosis and by selecting suitable particle size to avoid the entrapment of microspheres in non-target organs.

Hydroxypropyl methylcellulose based cephalexin extended release tablets: influence of tablet formulation, hardness and storage on in vitro release kinetics.

The object of this study was to develop hydroxypropyl methylcellulose (HPMC) based cephalexin extended release tablet, which can release the drug for six hours in predetermined rate. Twenty-one batches of cephalexin tablets were prepared by changing various physical and chemical parameters, in order to get required theoretical release profile. The influences of HPMC, microcrystalline cellulose powder (MCCP), granulation technique, wetting agent and tablet hardness on cephalexin release from HPMC based extended release tablets were studied. The formulated tablets were also characterized by physical and chemical parameters. The dissolution results showed that a higher amount of HPMC in tablet composition resulted in reduced drug release. Addition of MCCP resulted in faster drug release. Tablets prepared by dry granulation was released the drug slowly than the same prepared with a wet granulation technique. Addition of wetting agent in the tablets prepared with dry granulation technique showed slower release. An increase in tablet hardness resulted in faster drug release. Tablets prepared with a wet granulation technique and having a composition of 9.3% w/w HPMC with a hardness of 10-12 kg/cm(2) gave predicted release for 6 h. The in vitro release data was well fit in to Higuchi and Korsmeyer-Peppas model. Physical and chemical parameters of all formulated tablets were within acceptable limits. One batch among formulated twenty-one batches was successful and showed required theoretical release. The effect of storage on in vitro release and physicochemical parameters of successful batch was studied and was found to be in acceptable limits.

Eudragit NE30D based metformin/gliclazide extended release tablets: formulation, characterisation and in vitro release studies.

Metformin/Gliclazide extended release tablets were formulated with Eudragit NE30D by wet granulation technique. Two batches were prepared in order to study influence of drug polymer ratio on the tablet formation and in vitro drug release. The formulated tablets were characterized by disintegration time, hardness, friability, thickness, weight variation, and in vitro drug release. The percentage of polymer, with respect to Metformin/Gliclazide, required to produce tablets with acceptable qualities was 9 to 13.45. The percentage of polymer below this range released the drug immediately and above this range produced granules not suitable for tablet formation. The quantity of Metformin/Gliclazide present in the tablets and the release medium were estimated by a validated HPLC method. The formulated tablets had acceptable physicochemical characters and released the drug over 6-8 h. The data obtained from in vitro release studies were fitted with various kinetic models and was found to follow Higuchi kinetics.

Synthesis and pharmacological activities of 1,8-naphthyridine derivatives.

In the present study, a series of 2-substituted-4-methyl-7-amino/4,7-dimethyl-1,8-naphthyridines were synthesized and characterized by IR, 1H-NMR and elemental analysis. The compounds were investigated for anticonvulsant (125, 250 mg/kg), cardiac and antimicrobial activities. The compounds were screened for antibacterial activity against gram (+) bacteria (Staphylococcus epidermidis, Bacillus subtilis, Enterococcusfaecalis and Micrococcus luteus) and gram (-) bacteria (Proteus vulgaris, Pseudomonas aeruginosa, Escherichia coli and Salmonella typhi). All the compounds except 2-(3'-phenylaminopropyloxy)-4-methyl-7-amino-1,8-naphthyridine exhibited significant anticonvulsant activity. The anticonvulsant activity of 2-(3-morpholino-2'-hydroxypropyloxy)-4-methyl-7-amino-1,8-naphthyridine, 2-(3'-diphenylamino-2'-hydroxypropyloxy)-4-methyl-7-amino-1,8-naphthyridine and 2-(3'-diethanolamino-propyloxy)-4,7-dimethy-1,8-naphthyridine at the dose of 250 mg/kg were found to be equivalent to diazepam (5 mg/kg). Sympathetic blocking activity was observed with 2-(3'-phenylamino-2'-hydroxypropyloxy)-4-methyl-7-amino-1,8-naphthyridine, 2-(3'-diethanolamino-2'-hydroxypropyloxy)-4-methyl-7-amino-1,8-naphthyridine and 2-(3'-diphenylamino-2'-hydroxypropyloxy)-4-methyl-7-amino-1,8-naphthyridine only. All the compounds were devoid of antibacterial activity against the tested bacteria.

The effect of tablet formulation and hardness on in vitro release of cephalexin from Eudragit L100 based extended release tablets.

Eighteen batches of cephalexin extended release tablet were prepared by wet granulation method by using Eudragit L100. The effect of the concentration of Eudragit L100, microcrystalline cellulose and tablet hardness on cephalexin release was studied. The formulated tablets were also characterized for physical and chemical parameters. The dissolution results showed that a higher amount of Eudragit in tablet composition and higher tablet hardness resulted in reduced drug release. An increased amount of microcrystalline cellulose in tablet composition resulted in enhanced drug release. Tablet composition of 13.3% w/w Eudragit L100 and 6.6 to 8% w/w microcrystalline cellulose with hardness of 7-11 kg/cm2 gave predicted release for 6 h. The in vitro release was compared with a marketed tablet. Physical and chemical parameters of all formulated tablets were within acceptable limits. The effect of storage on in vitro release and physicochemical parameters of tablets was evaluated and two batches among formulated eighteen batches found to be in acceptable limits.