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of osmotic pressure and it is one of the most promising drug delivery technologies for
controlled drug delivery of drug. The highest degree of in-vivo in-vitro correlation (IVIVC)
can be achieved in case of OROS drug delivery system as drug release from OROS is not
affected by the physiological pH and hydrodynamic conditions of the body because of the
semipermeable nature of the rate-controlling membrane and the design of delivery orifice
used in osmotic systems. Therefore, forth extended release dosage form prepared was
OROS tablet. Out of the available OROS system, push pull osmotic device, which is widely
used OROS system, was selected to formulate extended release dosage form of S-
Metoprolol Succinate. Push pull osmotic pump contains bilayer tablet comprising active
layer and push layer. This bilayer tablet than coated with semipermeable membrane and
one delivery orifice was drilled on the active layer side to facilitate delivery of drug. For
preparation of OROS tablets of S-Metoprolol Succinate, low molecular weight hydrophilic
swellable polymer from polyethylene oxide range (i.e. Polyox) were evaluated and for
push layer higher molecular weight hydrophilic swellable polymer from polyethylene oxide
range (i.e. Polyox). Sodium chloride was used as an osmotic agent in push layer. Cellulose
acetate (CA 398-10) used as a semi permeable membrane and polyethylene glycol (PEG
3350) used as plasticizer. A lubricated blend of drug layer and a push layer were
evaluated for various physical tests and core tablets were evaluated for different physical
properties. The finished product was evaluated for drug release profile. Final formulation
was optimized using central composite design (CCD) where the effects of percentage
weight gain, concentration of sodium chloride and cellulose acetate to PEG 3350 ratio on
the drug release profile were investigated. Optimized formulation showed a comparable
dissolution profile to that of the innovator product in different dissolution media.
Optimized formulation was stable at different stability condition and all parameters were
found well within acceptance criteria.

Keywords: S-Metoprolol Succinate, Racemate, Extrusion and Spheronization, Fluid Bed
Process, MUPS, Osmotic Release Oral System, Central composite design.

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