Evaluation of anti-moisture effect of HPMC, Kollidon CL and Aerosil - 200 in hydrolysis affinity Clopidogrel-Aspirin tablet using Delta T Moister Sensor

Aspirin (2-acetyloxy benzoic acid) is one type of cyclooxygenase inhibitor and Clopidogrel bisulphate (methyl (s)-2-chlorophenyl (4,5,6,7-tetrahydothioeno-[3,2-C]pyridine-5-yl) acetate bisulphate) which is an ADP antagonist, are two major anti-thrombogenic agents 1,2,3 .Aspirin is effective to prevent the primary and secondary myocardial infarction, cardiovascular death and stroke 4,5,6 and Clopidogrel is a second generation thienopyridine with a better tolerability profile than first generation thienopyridines (ticlopidine).The combined dosage formulation of Aspirin and Clopidogrel Bisulphate is useful as antiplatelet agents.The combination of Clopidogrel and Aspirin is demonstrated for the treatment of acute coronary syndromes especially in Unstable Angina, and Percutaneous Coronary Interventions 6,7,8 .This combined formulation provides a greater inhibition of platelet activity than Aspirin alone in patients after recent ischemic stroke 9 .This combined antiplatelet therapy has an important role for patients with established cardiovascular disease.Combined use of these two drugs produces enhanced therapeutic effect.Aspirin and Clopidogrel both are esters and have a tendency to hydrolysis which reduces therapeutic activity 10 .Both the drugs are susceptible to neutral and oxidative-degradation, dry heat AbstractThe combined therapeutic effect of aspirin and clopidogrel is more potent than single one.This combined formulation is not stable due to their moisture affinity toward the hydrolysis reaction.The presence of moisture is a crucial factor in any formulation and causes sticking, picking, microbial growth, stability issues, lamination, friability.This combination formulation was designed using hydroxypropylmethyl cellulose 15 cps, Kollidon CL and Aerosil 200 in a controlled clean room class-I to stop the hydrolysis reaction.The tablets were made using slug method and hardness, disintegration, friability, dissolution, drug content, water activity, moisture content was determined.Kollidon CL and Aerosil 200 showed greater moisture reduction rate than HPMC 15 cps.The better anti-moisture effect of the excipient of Kollidon CL and Aerosil 200 was assured by the calculation of water activity using delta T sensor and isotherm, hysteresis.The quantity of excipients in the tablets was demonstrated for the significant affinity to moisture.The investigated simulated amount of Kollidon CL and Aerosil 200 showed the effective lower water activity in the delta T sensor.The mean moisture specification range was considered as 0.5-4.0%while the kollidon CL and Aerosol 200 showed moisture content of 1.32% and water activity (aw)of 0.014.In this study the Delta T sensor is used due to its significant reduction of dead time from 30% to 45% and moisture variation reduced at least 30% than other models treatment.