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Biomedical subjects

J Balasubramaniam

Publications and source records attributed to J Balasubramaniam.

15 recordsLinked to original sources

Development and evaluation of a novel floating in situ gelling system of amoxicillin for eradication of Helicobacter pylori.

The aim of this study was to develop a new intra-gastric floating in situ gelling system for controlled delivery of amoxicillin for the treatment of peptic ulcer disease caused by Helicobacter pylori (H. pylori). Gellan based amoxicillin floating in situ gelling systems (AFIG) were prepared by dissolving varying concentrations of gellan gum in deionized water containing sodium citrate, to which varying concentrations of drug and calcium carbonate, as gas-forming agent, was added and dissolved by stirring. The formulation variables like concentration of gellan gum and calcium carbonate significantly affected the in vitro drug release from the prepared AFIG. The in vivo H. pylori clearance efficacy of prepared AFIG in reference to amoxicillin suspension following repeated oral administration to H. pylori infected Mongolian gerbils was examined by polymerase chain reaction (PCR) technique and by a microbial culture method. AFIG showed a significant anti-H. pylori effect in the in vivo gerbil model. It was noted that the required amount of amoxicillin for eradication of H. pylori was 10 times less in AFIG than from the corresponding amoxicillin suspension. The results further substantiated that the prepared AFIG has feasibility of forming rigid gels in the gastric environment and eradicated H. pylori from the gastrointestinal tract more effectively than amoxicillin suspension because of the prolonged gastrointestinal residence time of the formulation.

Amoxicillin↗

Dissolution, bioavailability and ulcerogenic studies on piroxicam-nicotinamide solid dispersion formulations.

Solid dispersions with different ratios of Piroxicam and Nicotinamide (as a carrier) were prepared by fusion method. Drug-carrier interactions in the solid state were ascertained using phase-diagram, X-ray diffraction (XRD) and Differential scanning colorimetry (DSC). Select ratios of the formed piroxicam-nicotinamide solid dispersions and their corresponding physical mixtures were formulated into tablets and capsules. The dissolution characteristics of the formed solid dispersions, physical mixtures and their formulations were compared with pure piroxicam in 900 ml of 0.1 N HCl (pH 1.2) at 37 +/- 0.5 degrees C, 50 rpm using USP XXI paddle apparatus. Solid dispersion capsule PNC1 (containing 1:5--drug-carrier ratio solid dispersion) and the corresponding physical mixture capsule PNC1A were used for bioavailability studies in healthy human volunteers. Further, ulcer indices of the prepared solid dispersion and their corresponding physical mixture were compared with pure piroxicam in rats. The DSC, XRD and phase diagram indicated the formation of solid dispersed system. The prepared dispersion showed better dissolution than the corresponding physical mixture and pure drug. The fabricated formulation complied with the pharmacopoeial limits for physico-chemical properties and the solid dispersion capsules PNC1 and PNC2 (containing 1:9 ratio of drug to carrier solid dispersion) showed 3 and 6.6 fold increase and 3.2 and 8 fold increases in dissolution rate compared to the corresponding physical mixture capsules (PNC1A and PNC2A), respectively. The solid dispersion capsule PNC1 showed significantly higher absorption and dissolution and consequently better bioavailability than the corresponding physical mixture capsule (PNC1A) in healthy human volunteers. The ulcer indices of the prepared dispersions were significantly lower than the corresponding physical mixture and pure drug.

Animals↗

Evaluation of a new screening test for sickle cell haemoglobin.

A new kit for screening for sickle cell haemoglobin (haemoglobin S) has been evaluated. The kit is based on the principle that cells containing haemoglobin S, which have been induced to sickle by exposure to a reducing agent in a phosphate buffer, do not pass through a gel contained in microtubules. In theory, they can thus be distinguished from cells that do not contain haemoglobin S. In practice, the kit was found to be insensitive and unreliable for the detection of haemoglobin S. Homozygosity and heterozygosity for haemoglobin S could not be reliably distinguished. Similarly, patients with haemoglobin S who had been transfused could not be distinguished reliably from those who had not been transfused. In conclusion, unless improved performance can be demonstrated, use of this kit cannot be recommended.

Anemia, Sickle Cell↗

In vitro and in vivo characterization of scleral implants of indomethacin.

Scleral implants of indomethacin with sodium alginate as carrier were fabricated and evaluated for various physico-chemical properties such as uniformity of thickness, weight, drug content, surface pH, percent dissolution and water up-take capacity (swelling index). The effect of drug particle size, polymer concentration, drug loading, plasticizer concentration, and effects of physical reinforcement (freeze-thawing for 3 and 6 cycles) and chemical cross-linking with calcium chloride, on the in vitro drug release characteristics were evaluated. Selected batches of the implants were subjected to pharmacodynamic studies, after scleral placement, in uveitis induced (intravitreal injection of Bovine Serum Albumin (BSA)-50 micrograms/ml) rabbit eyes. The release of indomethacin from the prepared implants followed predominantly matrix diffusion kinetics. Swelling and moisture absorption/loss studies correlated well with the in vitro release studies. The pharmacodynamic studies showed a marked improvement in the various clinical parameters (congestion, keratitis, flare, clot, aqueous cells and synechias), in the implanted eye when compared to the control eye in the rabbits.

Alginates↗

Gellan-based scleral implants of indomethacin: in vitro and in vivo evaluation.

Film-type scleral implants of indomethacin with gellan gum were prepared by solvent casting and evaluated for uniformities of thickness, weight, drug content, and surface pH. The effect of plasticizers like glycerol, propylene glycol (PG), and polyethylene glycol 200, and 400 on the void volume of free gellan films (placebo) was calculated from the water content of the films. The drug release from the prepared implants was determined using a static dissolution set-up developed and optimized in our laboratory. Based on the results of the void volume and initial drug release studies, glycerol and PG were selected as the plasticizers for the gellan-based implants. The morphology of the drug-free films (containing 10% and 40% of PG) and the drug-loaded films (before and after dissolution and crosslinked) was studied using scanning electron microscopy. Further, the effect of plasticizer concentration, gellan concentration, effect of crosslinking technique, and duration of crosslinking using calcium chloride on in vitro drug release characteristics were evaluated. Selected batches of the implants were subjected to pharmacodynamic studies, after scleral placement, in uveitis-induced (intravitreal injection of bovine serum albumin 50 microg/ml) rabbit eyes. The release of indomethacin from the prepared implants followed matrix diffusion kinetics with diffusion co-efficient (n) values ranging between 0.358 to 0.708 and seemed to depend on both gellan and plasticizer concentration. Surface crosslinking with 10% calcium chloride for 8 hr retarded drug release (1.42 times less than noncrosslinked implant) and was optimum. The pharmacodynamic studies showed a marked improvement in the various clinical parameters (congestion, keratitis, flare, clot, aqueous cells, and synechias) in the implanted eye compared with the control eye in the rabbits. The scleral implants survived up to 3 weeks in vivo.

Animals↗

Niridazole biodegradable inserts for local long-term treatment of periodontitis: possible new life for an orphan drug.

Periodontal pocket inserts of niridazole (NZ) made with Resomer(R) (grades RG 503H and RG858, designated as RH and RG, respectively) were studied. Various formulation variables were evaluated to obtain a biodegradable delivery systems showing device degradation and drug depletion parallel to each other in vitro. Drug release from the prepared inserts was evaluated using a static dissolution setup (for 1 month). Incorporation of 3 parts of RG in 1 part of RH inserts caused a 50% decrease in the initial release rate. The RH-NZ inserts showed a spurt in release around the 10th day of the study, which coincided with the decrease in device weight, suggesting onset of device degradation. Pilot-scale clinical trials in 12 patients indicated improvements in clinical indices from the baseline values. The average pocket depth was reduced significantly (alpha = 0.05) from 6.34 +/- 1.86 mm at baseline to 5.94 +/- 0.28 mm after 28 days of treatment.

Absorbable Implants↗

Ion-activated in situ gelling systems for sustained ophthalmic delivery of ciprofloxacin hydrochloride.

The poor bioavailability and therapeutic response exhibited by the conventional ophthalmic solutions due to precorneal elimination of the drug may be overcome by the use of in situ gel forming systems that are instilled as drops into the eye and undergo a sol-gel transition in the cul-de-sac. Our present work describes the formulation and evaluation of an ophthalmic delivery system of an antibacterial agent, CPH, based on the concept of ion-activated in situ gelation. Gelrite gellan gum, a novel ophthalmic vehicle that gels in the presence of mono or divalent cations, present in the lacrimal fluid was used alone and in combinations with sodium alginate as the gelling agent. The developed formulations were therapeutically efficacious and provided sustained release of the drug over an 8-hr period in vitro.

Alginates↗

In vitro and in vivo characterization of scleral implant of indomethacin: role of plasticizer and cross-linking time.

Film-type scleral implants of indomethacin using sodium alginate and PEG 400 and 600 (3, 5, 8, and 10% w/w w.r.t. sodium alginate) as plasticizers were fabricated by solvent casting. The prepared implants were cross-linked by treatment with calcium chloride 10, 20, and 30% w/v solution, for periods between 1 to 24 hr. Uniformity of thickness, weight, and drug content and surface pH of the implants were evaluated. The influence of plasticizer type/concentration and crosslinking time/concentration of calcium chloride on indomethacin release was studied on a static dissolution setup developed by us. Selected batches of the implants were subjected to pharmacodynamic studies, after scleral placement, in uveitis-induced (intravitreal injection of bovine serum albumin 50 microg/ml) rabbit eyes. The release of indomethacin from the implants was influenced by the concentration and nature of plasticizers used. Chemical cross-linking with calcium chloride was successful in retarding the drug release. The pharmacodynamic studies showed a marked improvement in the various clinical parameters (congestion, keratitis, flare, clot, aqueous cells, and synechias) in the implanted eye when compared with the control eye in the rabbits. The implants survived for 2 weeks in vivo.

Animals↗

Novel therapeutic approaches for uveitis and retinitis.

A virtual increase in the number of patients undergoing immunosuppressant therapy and those suffering from AIDS has created a unique class of population suffering from virulent uveitis and retinopathies. A very common pathogen implicated in retinopathy in such patients is the cytomegalovirus (CMV).

Animals↗

Bioavailability studies on fast release formulations of indomethacin.

Indomethacin-nicotinamide solid dispersions were prepared by fusion method. Drug-carrier interaction in the liquid and solid states were studied using phase solubility data and differential scanning colorimetry (DSC). DSC revealed the formation of an eutectic mixture of indomethacin and nicotinamide. Tablets and capsules, formulated from the solid dispersions showed significantly better dissolution and enhanced absorption rate in human volunteers, compared to commercial capsule of indomethacin.

Adult↗