Formulation Development and Optimization of Reconstitutable Oral Suspension of Mycophenolate Mofetil

Abstract

Mycophenolate Mofetil (MMF) is an immunomodulator drug used in prevention of rejection of organ during organ transplant. MMF requires daily dose of 3.5 or 4.0 g/day depending upon the patient and disease state being treated. Thus with conventional dosage form having dose of 200 mg in capsule and 500 mg in tablet and patient will require twelve units and six units respectively each day. As an alternative dosage form, respectively reconstitutable oral suspension (200 mg/ml) will provide ease of administration and convenience. Formulation of reconstitutable oral suspension was carried out by direct blending approach and wet granulation (using FBP) approach Amongst them wet granulation (using FBP) was carried out for further study. Sorbitol (Neosorb P100T), citric acid (anhydrous), soybean lecithin, trisodium citrate, xanthan gum, methyl paraben, aspartame, mixed fruit flavor and colloidal silicon dioxide were used for formulation of reconstitutable oral suspension. During study, suspension was evaluated for various parameters like viscosity (600 -700 cps), pH (6 -7), deliverable volume (172 -178ml), % drug release in 20 min (81.5 -84.5%) and % assay of reconstituted suspension (98 -102%). Stability study of dry powder (40ºC/75%RH) and reconstituted suspension (30ºC/65%RH and 2-8ºC) was carried out for reproducible batch for one month and it was within preferred criteria. F2 value (88.53) indicated that reproducible batch was similar in terms of % drug release profile with compare to innovator product CellCept® (200mg/ml) oral suspension. Design space was identified using design expert software (Version 9.0) for selection of concentration of xanthan gum and soybean lecithin using 22 factorial designs with 3 center points.