Propranolol Drug Release Study

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The drug release study of Propranolol from the synthesized prodrugs9a and 9c proved that they hydrolyze significantly at pH 6.8 & 7.4. This proves the stability of prodrug at gastric pH and easily gets hydrolyzed at both blood and intestinal pH, and would be available for the action by significantly eliminating the problem of fast metabolism and local irritation when compared to the parent drug. The % CDR of 9c at pH 7.4 was found to be maximum i.e. 92% within 3 hrs and at pH 6.8 it is 86% but at pH 1.2 it is only 8.13%, whereas in case of 9a the % drug release is 83% at pH 7.4 and 71% in pH 6.8 but at pH 1.2 it is only 10.6%. The maximum drug release from the synthesized prodrugs was found at slightly alkaline pH, due
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On the 26th day, the animals were grouped and drugs were administered according to the dose to respective groups. Blood pressure was recorded as 0-5 hrs with 30 min interval by tail cuff method.9The hypertensive animals were divided into four groups (6 each)
Group I: Control – Receives 10% fructose solution
Group II: Standard – Receives Standard Drug Propranolol accordingly.
Group III: Receives 9c (15 mg/kg body weight of animal used)
Group IV: Receives 9a (15 mg/kg body weight of animal
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By considering the recorded Blood pressure data, among the synthesized derivatives, 9c has shown significant anti-hypertensive activity and prolonged duration of action when compared to the standard drug Propranolol but onset of action is slightly delayed than standard drug, which may be due to time required for ester hydrolysis. The reduction in Systolic Blood Pressure in case of 9c is more than that of the standard drug, Propranolol which suggests the probable synergistic effect of 2-phenyl indolizine moiety on hypertension, whereas in case of 9a which contains unsubstituted indolizine moiety condensed with Propranolol, there is no much significant reduction in Systolic Blood Pressure, which suggests no synergistic contribution of unsubstituted Indolizine ring on hypertension and its effect is same as standard

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