Development of Sustained Release of Gatifloxacin by Using Floating Oral in Situ Gelling System and

Gatifloxacin is end up being one of the potential medications against H. pylori infection. As conventional drug delivery systems do not remain in the stomach for delayed periods, they can't convey the Gatifloxacin to the site of infection in effective concentrations. Hence it planned to develop a new floating in situ gelling system of Gatifloxacin with increased residence time using sodium alginate as gelling polymer and HPMC as thickening agent with a potential of H. Pylori eradication. The formulations were evaluated on the basis of Pharmacopoeial specification. Clarity, visual appearance, pH, gelling capacity, viscosity, gelation, buoyancy, water uptake, density of gel, gel strength, drug content, assessment of drug release, release kinetics were carried out as per specifications and results were found to be complied with the Pharmacopoeial specification. The formulation F6 shows good result as compared to other formulation. The findings of prepared in situ gelling formulations of Gatifloxacin increased the gastric residence time and also float in the gastric condition.


Introduction
Gastric retention time can be drawn out by different strategies, for example, floating drug delivery system, polymeric boiadhesive system, high density system, swelling and expanding systems, modified-shape system, delayed gastric emptying devices etc.
Oral in situ gel forming system is also called as stomach specific or raft forming systems have given a reasonable method for giving the controlled drug delivery within stomach with upgraded gastro-retention. The tablet/capsule floating dosage forms are steady as contrast with liquids however the issue with them is that are expected to swallow as whole unit. If there should arise an occurrence of dosage adjustment these can't be broken in In this method, less viscosity solution is used, which undergo change in polymeric conformation when come in contact with the gastric liquids, and a viscous gel of density lower than the gastric fluids is the contact time. This low density gel formation called as raft not slow drug release 2 .

The most widely recognized pathogenic bacterial infections is
Helicobacter pylori. It is related with serious gastro duodenal sickness, including peptic ulcers, gastric lymphoma, and acute chronic gastritis 3 . H. pylori resides mainly in the gastric mucosa or at the interface between the mucous layer and the epithelial cells of the antral region of the stomach. Recently Gatifloxacin is proved to be one of the potential drugs against H. pylori infection. As conventional drug delivery systems do not remain in the stomach for prolonged periods, they are unable to deliver the Gatifloxacin to the site of infection in effective concentrations 5 . Therefore, it is necessary to design drug delivery systems that not only alleviate the shortcomings of conventional delivery vehicles but also deliver Gatifloxacin to the infected cell lines. A few analysts had arranged and revealed new Gatifloxacin formulations, such as floating tablets, mucoadhesive tablets and mucoadhesive microspheres, which were able to dwell in stomach for an extended period for more effective H. pylori annihilation 6,7 . The floating tablet is preferred for better and less variable gastric retention, but it has a limitation of

Determination of the visual appearance
All the formulations was visually inspect for their appearance and clarity.

Measurement of the pH
The pH for each of the formulations was measure using a calibrated pen pH meter. The readings was record three times for each of the formulation and the averages of the readings was consider 12 .

Determination of viscosity
Viscosities of the formulations are determined with the help of Brookfield's digital Viscometer using S21 spindle at 50 rpm and measurement was done for 6 times with fresh samples being used each time and the average reading was take.

In vitro buoyancy study
Pareek et al.

Measurement of water uptake by the gel
To conduct this study, the in situ gel formed in 40 ml of 0.1N HCl, pH 1.2 was use. From each of the formulation, the gel part was separate from the buffer and the excess buffer was blotted out with the help of Whatman filter paper. The gel was initially weighed and its weight was note, followed by the addition of 10 ml distilled water to this gel. After every 30 min interval, water was decant and weight of the gel was note and difference between initial and final weight was calculated and record 16 .

Measurement of density of gel
30 ml of the in situ formulation was poured into a beaker containing 50 ml of 0.1N HCl. 10 ml of the gel formed was take in measuring cylinder and weight of the gel was measured. Using the weight as well as the volume of the gel, the density was calculate. This method was followed for all the formulations 17 .

Measurement of gel strength
30 g of the gel was take in a 50 ml beaker and a 50 g weight was place on the center of the surface of the gel and allowed to penetrate through the gel. The time taken by the 50 g weight to penetrate 5 cm down through the gel was noted for all the formulations. The same method was followed for 6 times for each fresh formulation and average time was noted 18 .

In vitro drug release study of the in situ gel formulation
The drug release of the formulations was determined using a USP dissolution apparatus (Type II)  replenished with fresh medium. The samples collected were filtered, suitably diluted, and analyzed at 292 nm using UV spectrophotometer 10 .

Kinetic modeling
The prepared formulation was adopted to study the kinetics of drug release. The in vitro drug release data were analyzed by fitting them into different kinetic models namely zero-order, firstorder, Higuchi and Korsmeyer-Peppas in order to investigate the release mechanism of Gatifloxacin from the formulation.

Results and Discussions
The six different formulation (F1 to F6) of Gatifloxacin in situ gelling system were prepared by using sodium alginate as gelling polymer and HPMC as thickening agent.

Appearance and clarity
During preparation of in-situ gel of Gatifloxacin, the appearance and clarity of formulation on varying the concentration of polymer in drug has been observed. The appearance and clarity of Gatifloxacin formulation is displayed in table 2. It depicted that the uniformly distribution of drug in formulation.

pH
The pH of the various formulations observed and displayed in table 3. The pH of the formulation was found to be in range of 7.68±0.19 -8.05±0.34. The pH of all the formulations was within the orally acceptable range. Therefore, it will not cause any irritation on administration of the formulations.

In vitro gelation
The gelling capacity of all formulations demonstrated in table 3.
The formulations were free running and did not produce any gelation at room temperature. resulted in the gelation which remained for more than 12 h providing the sustained release of the drug, which concludes that as the concentration of anionic polymer increases the gelling capacity also increases.

Viscosity studies
The findings of viscosity of formulations are displayed in table 3.
The formulations showed an increase in viscosity with increasing the concentration of gel forming polymer sodium alginate as a consequence of the increase in chain interaction. The concentration of sodium alginate (500 mg and 750 mg) was found to produce a satisfactory viscosity increase which provides sustained release of the drug. Calcium carbonate also contributes to increasing the viscosity of the formulations.

In vitro buoyancy study
The results of Buoyancy studies are shown in Table 3

Density of gel
Density is an important evaluation parameter as far as the buoyancy ability of the gastroretentive dosage form is concerned. For the formulation to float on the gastric contents, it should have a density less than or equal to that of the gastric contents (~1.004 gcm −3 ). The density of all the formulations given in Table 3 has density less than the specified value. As a result, the floating of the gastroretentive in situ gel is promoted in the stomach.

Gel strength
All the formulations showed good gel strength which ranged from as low as 18.24 s for F1 to higher values of 55.17 for F6 formulations which have the combination of sodium alginate and polymer (Table 3)   formulations. These values are characteristic of anomalous kinetics (non-Fickian) and super case-II transport, suggesting that more than one mechanism may be involved in release kinetics, referring to combination of diffusion and erosion based drug release mechanism. This mechanism could result from an increased plasticization at the relaxing boundary.

Conclusion
The present study suggested that the Gatifloxacin has enhanced gastric residence time by formulating with sodium alginate as a gelling polymer and HPMC as a thickening agent. Further it was noted formulation slowly released Gatifloxacin for the 12 h.