Ethyl cellulose and hydroxypropyl methyl cellulose buoyant microspheres of metoprolol succinate: Influence of pH modifiers.

Introduction: Incorporation of pH modifier has been the usual strategy employed to enhance the dissolution of weakly basic drug from floating microspheres. Microspheres prepared using a combination of both ethyl cellulose (EC) and hydroxypropyl methylcellulose (HPMC) which shows highest release were utilize to investigate the effect of fumaric acid (FA), citric acid (CA), ascorbic acid (AA) and tartaric acid (TA) (all 5-20% w/w) incorporation on metoprolol succinate (MS) release.

Materials And Methods: EC, HPMC alone or in combination were used to prepare microspheres that floated in simulated gastric fluid and evaluated for a percent yield, drug entrapment, percent buoyancy and drug release. The higher drug release in combination (MS:HPMC:EC, 1:1:2) was selected for the evaluation of influence of pH modifiers on MS release. CA (5-20% w/w), AA (5-20% w/w), FA (5-20% w/w) and TA (5-20% w/w) were added and evaluated for drug release. Present investigation is directed to develop floating drug delivery system of MS by solvent evaporation technique.

Results: The microspheres of MS:HPMC:EC (1:1:2) exhibited the highest entrapment (74.36 ± 2.18). The best percentage yield was obtained at MS:HPMC (1:1) (83.96 ± 1.50) and combination of MS:HPMC:EC (1:1:2) (79.23 ± 1.63).

Conclusion: MS release from the prepared microspheres was influenced by changing MS-polymer, MS-polymer-polymer ratio and pH modifier. Although significant increment in MS release was observed with CA (20% w/w), TA (20% w/w) and AA (20% w/w), addition of 20% w/w FA demonstrated more pronounced and significant increase in drug entrapment as well as release from MS:HPMC:EC (1:1:2) buoyant microspheres.