Formulation, evaluation and optimization of sustained release matrix tablets of captopril.

Sustained release matrix tablet is a delivery system by which the drug can be delivered at a controlled rate for long period of time. The present study aims at formulation, evaluation and optimization of captopril matrix tablets. A 3(2) full factorial design was adopted and all 9 batches were prepared by wet granulation method. Prepared granules and tablets were evaluated for precompression and postcompression characteristics respectively. Check point analysis was applied to the observations and the formula of the tablet was optimized. Optimized formula, F6 showed zero order drug release kinetics for the time period of 24 hours i.e. 17.55% release at the end of 2 hours, 53.4% release at the end of 12 hours and 100.24% release at the end of 24 hours. The results revealed that concentration of matrix forming agent and solution of granulating agent significantly affected in vitro drug release profile.

The goal of any drug delivery system is to provide a therapeutic amount of drug at the target site in the body. It aims to achieve and maintain the desired drug concentration within body for required time period.[12] Matrix tablet system is one of the sustained drug delivery systems and widely used for the conditions where a prolonged drug concentration within the blood is desired i.e. in the conditions like hypertension, rheumatoid arthritis, hyperlipidaemia and many more. Captopril is an angiotensin converting enzyme inhibitor, used in the treatment of hypertension and fulfills all the criterias, required to be formulated as a matrix tablet. Although researchers have formulated captopril as microspheres, elementary osmotic pump tablets and bilayer floating tablets, if ease of scale up and its feasibility issues are considered, matrix tablet is the most suitable formulation.[3-5] Release of a freely soluble drug can be retarded using an appropriate combinations of hydrophilic and hydrophobic polymers matrices.[6-9] In present study, captopril matrix tablets have been formulated using hydrophilic polymer as a matrix forming agent and solution of hydrophobic polymer as a granulating agent.

Materials and Methods

Hydroxypropylmethylcellulose (HPMC) K4M and Ethyl Cellulose (EC) were purchased from Qualikems Pvt Ltd. Captopril was obtained as a gift sample from Astra Lifecare (India) Pvt. Ltd.

Method utilized to manufacture the matrix tablets was wet granulation. HPMC K4M polymer was used as hydrophilic matrix forming agent while solution of hydrophobic polymer EC in ethanol was used as granulating agent. 32 full factorial design was applied to the experiment and total 9 batches of 500 mg tablets were formulated. The two independent factors selected were concentration of matrix forming agent (X1) and concentration of solution of granulating agent (X2). The dependent variables considered, to optimize the tablets were hardness, % friability and in vitro drug dissolution profile.

Results and Discussion

The granules prepared were evaluated for flow properties and the compressed tablets were evaluated for hardness, % friability, drug content uniformity, weight variation and in vitro dissolution profile. Results of all the parameters are mentioned along with the standard deviation in Table 2. It can be seen from the result that granules have flow properties within the range of ‘good flow properties’ and therefore the blends are suitable for wet granulation. Tablets of each formula were sufficiently hard that they all passed the test of friability.[1011] Moreover all the formulae passed the test of weight Variation and content uniformity. Results of in vitro drug dissolution showed that as the concentration of the HPMC K4M increases, release of drug is retarted; moreover the increase in concentration of EC solution further retarded the release and so, zero order release could be achieved.

Table 2

Evaluation of granules

Conclusion

The sustained release matrix tablets of captopril, prepared by wet granulation method, showed acceptable pre-compression properties, post compression properties and satisfactory drug release up to 24 hrs in controlled manner. The multiple regression analysis of the results led to be equations that describe adequately the influence of the selected variables, concentration of HPMC K4M and concentration of EC in ethanol on the responses under study. The check point analysis led to the optimum values (X1 at +1 and X2 at 0 level i.e. formula F6) of the factors at which the produced tablets showed drug release up to 24 hrs in controlled manner.

Table 1

Levels of factors