Gastroretentive drug delivery systems for the treatment of Helicobacter pylori

Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial infections and is found in the stomachs of approximately half of the world’s population. It is the primary known cause of gastritis, gastroduodenal ulcer disease and gastric cancer. However, combined drug therapy as the general treatment in the clinic, the rise of antibiotic-resistant bacteria, adverse reactions and poor patient compliance are major obstacles to the eradication of H. pylori. Oral site-specific drug delivery systems that could increase the longevity of the treatment agent at the target site might improve the therapeutic effect and avoid side effects. Gastroretentive drug delivery systems potentially prolong the gastric retention time and controlled/sustained release of a drug, thereby increasing the concentration of the drug at the application site, potentially improving its bioavailability and reducing the necessary dosage. Recommended gastroretentive drug delivery systems for enhancing local drug delivery include floating systems, bioadhesive systems and expandable systems. In this review, we summarize the important physiological parameters of the gastrointestinal tract that affect the gastric residence time. We then focus on various aspects useful in the development of gastroretentive drug delivery systems, including current trends and the progress of novel forms, especially with respect to their application for the treatment of H. pylori infections.

In vitro and in vivo evaluation of gastroretentive floating drug delivery system of ofloxacin

This study aimed to develop hydrophilicmatrix based controlled release gastroretentive drug delivery system of ofloxacin and conducting its in vitro and in vivo evaluations.Effervescent floating gastroretentive drug delivery system of ofloxacin was prepared utilizing Boxe Behnken statistical design with 3 factors,3 levels and 15 experimental trials.Formulation optimization was done by setting targets on selected responses.In vivo studies were carried out for the optimized formulation with 12 healthy human volunteers and obtained pharmacokinetic parameters were compared with themarketed once daily formulation,“Zanocin OD”.Optimized formulation showed satisfactory controlled in vitro drug release for more than 12 h with excellent buoyancy properties(floating lag time<1 min,floating duration>16 h).Optimized and marketed formulations were found to have similar in vitro release profile(f2¼79.22)and also were found to be bioequivalent.Serum ofloxacin concentration was well maintained above its reported minimum inhibitory concentrations for most of the pathogens for sufficiently longer duration.Cmax and AUC values of optimized formulation were found to be significantly higher than of marketed product despite their bioequivalence.Bettertherapeutic effect can be expected since ofloxacin exhibits concentration dependent killing.Hence,gastroretention can be a promising approach to enhance bioavailability of ofloxacin with narrow absorption window in upper GIT.

Development and characterization of amoxicillin loaded floating microballoons for the treatment of Helicobacter pylori induced gastric ulcer

The current communication reports in vitro characterization of the optimized hollow floating microballoons of amoxicillin on the basis of micromeritic properties and in vitro minimum inhibitory concentration(MIC).Amoxicillin loaded hollow microballoons were prepared by emulsion solvent diffusion method.The morphological characterization was done on the basis of scanning electron microscopy(SEM).Fourier Transformed Infrared Spectroscopy(FTIR)was used to investigate drugepolymer interactions.The correlation between the in vitro buoyancy of microballoons and their physical properties,e.g.density and porosity were elucidated.The results of FTIR spectroscopy revealed the absence of any drugepolymer interactions.The porosity values of more than 69%and diameter to thickness ratio greater than 2.90,proved a high cavity volume within the microballoons in all size ranges.The spherical shape of microballoons with hollow internal cavity was confirmed from SEM photomicrographs.The in vitro MIC results showed a sustained drug effect from the microballoons.In conclusion,it can be said that the developed microballoons can be used for the effective treatment of Helicobacter pylori induced gastric ulcer.

Recent advances in alginate based gastroretentive technologies for drug delivery applications

The efficacy of orally delivered medicines can be maximized through enhancing the gastric residence period and modifying the drug release pattern according to therapeutic need.Several technologies were investigated through recent years for increasing gastric retention of medicines.Biopolymers are one of the widely studied materials for increasing the retention of drug delivery systems in the stomach region.The biodegradability,biocompatibility and non-toxic behavior in combination with the easy fabrication technologies has made biopolymers an interesting option to pharmaceutical scientists for developing gastroretentive drug delivery systems(GRDDS).Several gastroretentive approaches are reported to be efficacious to localize the drug delivery system in the gastric region.Alginates are commonly employed polysaccharide for developing various GRDDS including low density systems,mucoadhesive systems,swellable systems,hydrogel forming systems,in situ gelling systems,raft forming systems,magnetic systems.The abundant availability from marine and bacterial sources in combination with its attractive physicochemical nature has encouraged pharmaceutical researchers to investigate its suitability in developing various drug delivery system.The mucoadhesive,hydrogel forming and raft forming behavior of alginates makes alginate suitable for GRDDS.The attractive properties of alginate makes it a useful biopolymer in the biomedical field.This review focuses on the source and chemistry of alginates and describes the applications of alginates in developing novel gastroretentive drug delivery systems.

Design of a gastroretentive mucoadhesive dosage form of furosemide for controlled release

The aim of the present study was to develop and characterize a gastroretentive dosage form suitable for controlled drug release.It consists of a drug loaded polymeric film made up of a bilayer of immediate(IR)and controlled release(CR)layers folded into a hard gelatin capsule.Gast roretention results from unfolding and swelling of the film and its bioadhesion to the gastric.mucosa.Furosemide,a drug with a narrow absorption window,was selected as the model drug.Inclusion of hydroxypropyl β-cyclodextrin in both layers and Carbopol■ 971P NF in the CR layer of the bilayer film resulted in optimum drug release,bioadhesion and mechanical properties.The film with zig-zag folding in the capsule was shown to unfold and swell under acidic conditions and provide IR of drugover 1 hand CR for up to 12 h in acidic medium.X-ray diffraction,differential scanning calorimetry and scanning electron microscopy revealed uniform dispersion of furosemide in the polymeric matrices.The results indicate the dosage form is gastroretentive and can provide controlled release of drugs with narrow therapeutic wind ows.

Discovery and preclinical development of ⅢM-160, a Bergenia ciliatabased anti-inflammatory and anti-arthritic botanical drug candidate

Objective: Bergenia ciliata(Haw.) Sternb. is used in the Indian traditional system of medicine to treat various ailments including rheumatism and to heal wounds. The objective of the present study was to perform a preclinical characterization of the B. ciliata-based botanical extract IIIM-160.Methods: ⅢM-160 was chemically standardized and analyzed for heavy metal content, aflatoxins,pesticides and microbial load. The in vitro and in vivo efficacies were determined in suitable models of inflammation, arthritis and nociception. An acute oral toxicity study was performed in Swiss albino mice.A suitable oral formulation was developed and characterized.Results: Bergenin was found to be the major component(9.1% w/w) of ⅢM-160. The botanical lead displayed inhibition of lipopolysaccharide-induced production of proinflammatory cytokines in THP-1 cells, with selectivity toward interleukin-6(IL-6) and had an excellent safety-window. It showed anti-inflammatory, anti-arthritic and antinociceptive activity in animal models and was not toxic at oral doses up to 2 g/kg in Swiss-albino mice. The gastroretentive, sustained-release capsule formulation showed sustained-release of the bergenin over the period of 24 h, resulting in improved plasma-exposure of bergenin in Sprague–Dawley rats.Conclusion: The dual-activity of IL-6 inhibition and antinociception marks the suitability of ⅢM-160 for treating rheumatoid arthritis. This study will serve as the benchmark for further research on this botanical formulation.