Design and Optimisation of Extended Release Metoprolol Succinate Formulation Using Melt Granulation Technique

Metoprolol succinate (M.succinate), a BCS Class I drug is the most widely prescribed anti-hypertensive drug and is considered to be safe. Owing to its high solubility, fabrication of an extended release matrix formulation becomes extremely challenging. Hydrophilic matrix polymers are the preferred systems for developing an extended release formulation. However, for highly soluble drugs, it fails to retard drug release alone thus necessitating addition of other hydrophilic or lipophilic release retardants. Objective: The objective of the present work was to develop extended release tablets of m.succinate by melt granulation technique using a combination of hydrophilic swellable polymer (HPMC) and meltable binder. Methods: Optimisation of the formulation was carried out with respect to polymer type (varying viscosity grades), HPMC concentration (10-50%), nature of meltable binders (stearic acid, glycerylmonostearate, hydrogenated soyabean oil and PEG 6000) and type of diluents (MCC, lactose, DCP). Results: A combination of stearic acid and HPMC K100M could effectively extend release of m.succinate for 24 hours. Moreover, factors like drug to HPMC ratio and drug to stearic acid ratio were found to have significant effect on m.succinate release.The gel texture analysis of the tablet compacts provided good correlation of gel layer thickness and strength upon hydration with the release pattern and swelling behavior. The tablets were found to be stable for a period of six months. Conclusion: Melt granulation technique was successfully attempted to formulate stable extended release matrices of m.succinate, a highly water soluble drug.