Design and characterization of controlled release tablet of metoprolol.

Metoprolol succinate is a selective beta-adrenergic receptor blocker useful in treatment of hypertension, angina and heart failure. The purpose of the present work was to design and evaluate controlled release matrix type tablet of Metoprolo succinate using HPMC K15M and Eudragit (RLPO and RSPO) as a matrix forming agents. Effect of various polymer alone and combinations were studied in pH 1.2 buffer using USP type II paddle at 50 rpm. HPMC was used to form firm gel with Eudragit polymer. Formulation with Equal proportion (1:1) of Eudragit RSPO and RLPO showed optimum drug release t(50)=7 hrs and t(100)=16 hrs indicate optimum permeability for drug release from matrix. The drug release mechanism was predominantly found to be Non-Fickian diffusion controlled.

Metoprolol ((+)-1-(isopropyl amino)-3-[p-(2-methoxyethyl)]-2-propanol succinate) is a selective beta-adrenergic receptor blocker useful in treatment of hypertension, angina and heart failure. Metoprolol succinate is a white crystalline powder with high aqueous solubility and high permeability throughout gastrointestinal tract. Half-life of metoprolol succinate ranges from 3 to 7 hrs.[12]

Materials and Methods

The present research work was undertaken to design low-cost modified release (24 h) tablets of metoprolol succinate using HPMC K15M and Eudragit (RLPO and RSPO) as a matrixing agents. The reason of using combinations of such polymers was to overcome the disadvantages of individual matrix forming agents. Hydroxypropyl methyl cellulose hydrates quickly and forms firm gel. Typical sustained release formulations of metoprolol 100 mg are listed in Table 1. Tablets were made by using metoprolol (100 mg each tablet), HPMC (release retardant hydrophilic polymer), Eudragit and Lactose, by wet granulation process with PVP K30 (in isopropyl alcohol). Compression was done on a 10 station tablet machine (Rimek mini press India). The effects of polymer on drug release were studied in pH 1.2 buffer using USP type II apparatus at 50 rpm. Drug release and drug content was analyzed spectrophotometrically at 272 nm (UV spectrophotometer, Jasco) with validated UV method.

Table 1

Formulation trials

Results and Discussion

All the batches were evaluated for weight variation, hardness, friability, assay and found within acceptable limits of pharmacopoeia.[34] In-vitro drug release characterized with dissolution testing in Electro lab USP apparatus with 1.2 pH buffers. The cumulative drug release showed in Figure 1. It showed that drug release was very retarded in F-1 due to high proportion of Eudragit and HPMC polymers. F-3 formulation showed optimum drug release t50=7 hr and t100=16 hr. Formulation F-2 release was slower that F-4 because of low permeability of RSPO than RLPO. Equal proportion (1:1) of RSPO and RLPO made an optimum permeability for drug release from matrix. The data obtained from in-vitro dissolution studies were fitted in different models viz. zero order, first order, higuchi model and peppas model. The drug release mechanism was predominantly found to be Non-Fickian diffusion controlled. Release profile also showed a tendency to follow higuchi kinetics.

Figure 1

Cumulative drug release profile

Conclusion

It can be concluded formulation with desired drug release achieved with combination of Eudragit RLPO and RSPO in ratio of 1:1. The addition of gel forming polymer (HPMC) were essential to achieve stable and persistent gel formed by hydration of HPMC polymer. The results of present investigation shows the prepared metoprolol Tables were found to have good controlled release properties with controlled Non-Fickian diffusion.