Background: Depression is the one of the largest reasons of non-fatal health loss worldwide. Second-generation antidepressant drugs are the first-line therapy for pharmacological management of depression. Improvement in the use of these drugs is significant in lowering the burden of depression. Venlafaxine is a unique antidepressant drug including a wide range of antidepressant activity and a safety profile that are corresponding to serotonin selective reuptake inhibitors.

Aim: To enhance the bioavailability & half- life of Venlafaxine Hcl drug by using Ion gelation method using various grade polymers of HPMC such as HPMC K4M, HPMC K 15M, HPMC K100M & HPMC 15cps depends on their viscosity. Objective: The development of sustained release microspheres of Venlafaxine Hcl.

Method: The solubility of venlafaxine was studied in various solvents. Microspheres with different compositions were formulated and optimized. Selected formulation of microspheres contained high viscosity grade polymer and were evaluated for parameters such as drug content, particle size and in vitro drug release etc. Optimized microspheres formulation was incorporated in HPMC 15CPS and was evaluated for in vitro and stability.

Result: The FTIR shows the detect the functional group in Venlafaxine Hcl active drug. The UV analysis of Venlafaxine Hcl shows absorbance at 226 nm. The results give prepared microspheres enhanced drug content, drug entrapment efficiency, bulk density, tapped density, Housner’s ratio, carr’s index, Angle of repose. In the optimized F4 (HPMC 15cps+drug) trial which release Venlafaxine Hcl. 16.9±1.2 % in 1^st hr. & remaining drug released upto 16 hrs which is 96.2 ±2.45%.

Conclusion: The present study is aimed at development of a simple, rapid and useful method for identification of the venlafaxine and its metabolites in the microbial culture media. Results indicated that the microspheres has potential for sustained action of drug release and may act as a promising tool to enhance percutaneous delivery of venlafaxine.