in-situ gel

The principle purpose of this research work was to enhance oral bioavailability of vardenafil through formulation into gastroretentive in-situ gelling system using different concentrations of sodium alginate as gelling polymer, calcium carbonate as gas providing agent and source of calcium ion necessary for ionic gelation, calcium chloride as cross linking agent and sodium citrate as fluidity maintaining agent. The prepared batches were subjected to various evaluation parameters like viscosity, pH, floating lag time and floating period, gelling capacity and drug content. All prepared batches were clear solutions with pH ranges from 6.9 to 7.9. The viscosity before gelation ranges from 54 to 480 cp and after gelation from 435 to 5321 cp. All prepared batches float after few seconds and remain buoyant for more than 12 hours. They convert into gel 1-2 second or immediately after entering 0.1N Hcl pH1.2. The drug distributed homogeneously within prepared in-situ gel with drug content fall within the range of 94.6 to 100.1%. An increase in the concentration of sodium alginate, calcium carbonate and calcium chloride retard the drug release from the prepared in-situ gel. The formulation batch F4 which showed reasonable viscosity, prolonged floating period and sustained vardenafil release was selected for further in-vivo investigation. Formulation of vardenafil into in-situ gel increased tmax and decreased cmax thus enhancing its bioavailability.

Conventional liquid ophthalmic formulations are most convenient from patient point of view. But these formulation shows low bioavailability because of a constant lachrymal drainage in the eye which leads to frequent dosing. Moreover, the absorption of the drug drained through the nasolacrymal duct may result in undesirable side effects. To overcome these limitation different approaches has been applied such as ointment, gel, cream etc. These ophthalmic formulations also fails to show desired therapeutic responses because of their own disadvantages such as ointment makes blurred vision. So two different systems was combined together as niosomes and in-situ gel by incorporating niosomes in in-situ gel formulation so that it is easy to administered and retain at the site for prolong period of time. The Ofloxacin (OFL), a second generation fluoroquinolone derivative used in eye infections needs frequent dosing in its solution form. Vesicular system reported prolonged and controlled action at corneal surface but it has again limitation of drainage along tear produced.  In this, first niosomes containing ofloxacin were prepared by applying 32 full factorial designs and evaluated for its vesicle size, percent entrapment, in-vitro drug release kinetics and their stability. Also in-situ gel formulation was prepared by dispersing the niosomes in solution of carbopol 940 and Hydroxy Propyl Methyl Cellulose (HPMC) K4M. In-vitro drug release kinetics from niosomal in-situ gel formulation indicates that the minimum inhibitory concentration (MIC) of drug (4 μg/ml) was achieved within 1-2 hrs (batch G1-G9).

As an isolated organ, eye is very difficult to study from a drug delivery point of view. Ophthalmic drug delivery is extremely interesting and highly challenging endeavours. In recent scenario, most eye-diseases are treated with topical application of eye-drops. But these conventional eye-drops have two major problems. 1) It needs frequent administration at every 4 hours or 1 hour if the infection is severe and 2) Formation of crystalline deposits on cornea due to its pH-dependent solubility which is very low. In order to provide the solution to above problems many new formulations have been developed, which include nanosuspension, nanoemulsion, inserts, hydrogels, in-situ gel, etc. The poor bioavailability of ophthalmic solution caused by dilution and drainage from the eye can be overcome by using in-situ forming ophthalmic drug delivery system prepared from polymers that exhibit reversible liquid-gel phase transition. The developed formulation provides better drug product effectiveness, reliability, stability, safety, non-irritancy and prolonged release. Thus, it’s a viable alternative to conventional eye-drops by virtue of its ability to enhance bioavailability through its longer pre-corneal residence time & ability to provide prolonged drug release upto 8 hours. The main important factor is the reduced frequency & the ease of installation resulting in better patient acceptance. Keywords: Ophthalmic delivery, in-situ gel, polymers, liquid-gel phase transition, pre-corneal residence time, prolonged drug release.