Page 36 - 2019

Ph.D.
(Parmacy)
FORMULATION AND EVALUATION OF S-METOPROLOL SUCCINATE
EXTENDED RELEASE DOSAGE FORMS

Ph.D. Scholar : Patel Dipesh Vishnuprasad
Research Supervisor : Dr. B. G. Prajapati

Regi. No.: 14146021003
Abstract :
In pharmaceutical industries, many APIs are given as racemate containing 50:50 mixture
of complementary enantiomer. Nowadays, many regulatory authorities giving more
emphasis on developing the dosage form containing single enantiomer. Sometime single
enantiomer may give more beneficial effect over mixture. Sometime single enantiomer
may give opposite action compared to racemate. Metoprolol Succinate is widely used
beta blocker, which commercially available as a racemic mixture of S and R isomer in
50:50 ratio. Beta-1 blocking activity is mainly due to the S-isomer while R-isomer gives
beta-2 blocking activity. The unwanted administration of the non-beta-1-blocking R-
enantiomer, which makes up 50% of racemate, puts the patient at an increased risk of
side-effects, drug interactions and loss of cardio selectivity with up-titration of dosing.
The Major objective of the present investigation is to develop extended release dosage
form of S-Metoprolol Succinate as it is BCS class-I drug and having a half-life of 3-7 hrs
which makes it a better candidate for preparation of the extended release dosage forms.
One of the most widely used approach to make extended release dosage form is to
formulate matrix tablets. But one of the major disadvantage of matrix tablets is dose
dumping and can cause severe side effect due to dose dumping. Hence, to overcome this
disadvantage and to take advantage of beta-1 blockage activity of S-Metoprolol
Succinate, extended release pellets of S-Metoprolol Succinate were prepared. Pellets act
as individual system and due to this there is a very less chance of dose dumping of
drugs. Out of available technique for preparation of pellets, extrusion and spheronization
technique and fluid bed technique were used.

For preparation of extended release pellets by extrusion and spheronization, first drug
pellets were formulated using microcrystalline cellulose and lactose monohydrate as
diluents and hypromellose 5 cps as a binder. The different ratio of microcrystalline
cellulose and lactose monohydrate were evaluated and binder concentration was also
optimized. Prepared drug pellets were subjected to different evaluation tests like, bulk
density, particle size distribution and assay. Process parameters like spheronization
speed and time for spheronization were also optimized to get desired particle size of drug
pellets. Optimized drug pellets were coated using ethyl cellulose as extended release

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