Modified pH independent/ time controlled explosion system (TES) for targeted drug delivery in the lower intestinal tract: Formulation and pharmacokinetic evaluation in healthy volunteers

Abstract

The current work aimed to formulate a modified pH independent/time controlled release tablet for delayed drug delivery. The effect of different coating levels and polymer combination on drug release was investigated. Propranolol HCl (PRO) was chosen as a freely water soluble model drug. Statistical analysis of data revealed the significant (P < 0.05) influences of (i) coating level of swelling layer (SL), (ii) Different ethyl cellulose/hydrophilic polymer combination in rupturable layer and (iii) coating level of the rupturable layer (RL) on tL (lag time) and t90 (time for 90% drug release). The best achieved system; formed of 10% coating level croscarmellose sodium as inner swelling layer, 7% coating level of ethylcellulose/polyethylene oxide 205 (50:50) as an outer rupturable layer showed a tL of (10 h) followed by 90% drug release in the following 2 h. The in vivo pharmacokinetics of PRO following oral administration of the best achieved system (PF8) and Inderal® were assessed in healthy volunteers. The in vivo studies showed drug release of PRO following a tLof 6 h and a tmax of 8 h. The developed systems pave the way for delayed pulsatile release of other water soluble drugs for pH independent delayed drug delivery.