Design and evaluation of floating drug delivery system of an antihypertensive drug using different natural polymers

In the present study, an attempt was made to formulate individually the floating tablet of Eprosartan mesilate and Acebutolol hydrochloride by effervesecent approach comparing various synthetic and natural polymers by direct compression method to increase the gastric retention of the drug and thus increases the bioavailability of the drug. The principle of gastro-retentive dosage form is to reduce the density of the dosage form less than the density of gastric fluid to increase the gastric residence time by means of effervescent approach using sodium bicarbonate and citric acid as effervescent agent with different natural and synthetic polymers in this research. Intiallly, the procured drugs were identified by FTIR. Then, formulation of floating tablets of Eprosartan mesilate was done in three different stages with Eprosartan mesilate like to study the effect of different polymer on swelling index of the floating tablet, effect of effervescent agent on in vitro buoyancy studies. The results of above two stages were used to eliminate each one polymer from natural and synthetic sources and also to determine the concentration of effervescent agent in terms of ratio used to formulate floating tablets of Eprosartan mesilate in the third stage of formulation development. The result of third stage was used to formulate floating tablets of Acebutolol hydrochloride. From the results of the first stage of formulation development of floating tablets of Eprosartan mesilate, based on swelling index, ethyl cellulose in synthetic source and sodium alginate in natural source were omitted for further screening due to its low swelling index than formulations containing other polymers which may be due to no water absorption capacity of hydrophobic polymer, ethyl cellulose to swell and less water absorption capacity of hydrophillic polymer, sodium alginate to hydrate and swell because of less viscosity of polymer. From the results of the second stage of formulation development of floating tablets of Eprosartan mesilate, based on in vitro buoyancy studies, the highest ratio of sodium bicarbonate and citric acid was used for further formulation devolpment. From the results of the first and second stage of formulation development of floating tablets of Eprosartan mesilate, shortlisted polymers and highest ratio of sodium bicarbonate and citric acid were used to formulate floating tablets of Eprosartan mesilate. From these formulations based on in vitro buoyancy (floating lag time and total floating time), uniformity of drug content and in vitro dissolution studies, formulation containing karaya gum (E7) was selected as best formulation in terms of least floating lag time of 1 sec, total floating time of 580 min, 98.47% released at the end of 600min. It was then subjected to release kinetics analysis and confirmed from the highest correlation coefficient that it follows zero-order nonfickian diffusion controlled system. The best formulation was subjected to drug–excipient compatibility studies and compared with FTIR of pure drug found that there was no interaction with drug and excipients. It was then subjected to stability studies and found that there was no drastic changes in analysed post-compression parameters. It was then analyzed for in vivo experiments like in vivo X-ray studies and in vivo pharmacokinetic studies for predicting its buoyancy and drug release and comparing with in vitro parameters. From the results it was found that buoyancy and was maintained for 10 h in vivo similar to in vitro results and sustained drug release was noticed in vivo similar to in vitro results concluded sustained drug delivery system was achieved. From the above discussed results it was concluded that floating tablet of Eprosartan mesilate containing karaya gum (E7) prolongs the retention of dosage form in gastric area for longer time and thus minimizes the fluctuation in plasma concentration of the drug by frequent dosing of conventional immediate release dosage form. From the results of formulation development of floating tablets of Eprosartan mesilate, shortlisted polymers and highest ratio of sodium bicarbonate and citric acid were used to formulate floating tablets of Acebutolol hydrochloride. From these formulations based on in vitro buoyancy (floating lag time and total floating time), uniformity of drug content and in vitro dissolution studies, formulation containing karaya gum (A 7) was selected as best formulation in terms of least floating lag time of 1 sec, total floating time of 590 min, 98.91% released at the end of 600 min. It 139 was then subjected to release kinetics analysis and confirmed from the highest correlation coefficient that it follows zero-order non-fickian diffusion controlled system. The best formulation was subjected to drug–excipient compatibility studies and compared with FTIR of pure drug found that there was no interaction with drug and excipients. It was then subjected to stability studies and found that there was no drastic change in analysed post-compression parameters. It was then analyzed for in vivo experiments like in vivo X-ray studies and in vivo pharmacokinetic studies for predicting its buoyancy and drug release and comparing with in vitro parameters. From the results it was found that buoyancy and was maintained for 10 h in vivo similar to in vitro results and sustained drug release was noticed in vivo similar to in vitro results concluded sustained drug delivery system was achieved. From the above discussed results it was concluded that floating tablet of Acebutolol hydrochloride containing karaya gum (A7) prolongs the retention of dosage form in gastric area for longer time and thus minimizes the fluctuation in plasma concentration of the drug by frequent dosing of conventional immediate release dosage form. IMPACT OF THE STUDY: Floating drug delivery system offers various future potential like reducing fluctuations in the plasma level of drug resulted from delayed gastric emptying and also by reducing frequent administration of the drug. This delivery system is a beneficial strategy for the local treatment of gastric and duodenal cancers. The buoyancy concept can be utilized in the development of various anti-reflux formulations and these are potential to treat the Parkinson’s disease. In the present research an attempt was made to solve a common critical issue related to the rational development of FDDS include the correlation between prolonged GRT and sustained release and pharmacokinetic characteristics. This created a path of transition from developmental level to the manufacturing and commercial level of gastro-retentive drug delivery system. Further trials could be attempted in future on clinical studies for these best formulations of floating tablet of Acebutolol hydrochloride and Eprosartan mesilate separately.