Abstract :
In the present study, an effort was made to develop the pulsatile drug delivery of Losartan potassium to the colon. A
time delayed capsule was prepared by sealing the microspheres inside the insoluble hard gelatin capsule body with
erodible hydrogel plug. The microspheres were prepared by emulsion solvent evaporation technique.. Optimized
microsphere formulations were selected based on dissolution studies. The entire device was enteric coated, so that
the variability in gastric emptying time can be overcome and a colon-specific release can be achieved. Hydrogel
plug (HPMCK100 and lactose in 1:1 ratio) having 4.5kg/cm2 hardness and 100 mg weight was placed in the capsule
opening and found that it was satisfactory to retard the drug release in small intestinal fluid and to eject out the
plug in colonic fluid and releasing the microspheres into colonic fluid after a lag time criterion of 5 hours. In order
to simulate the pH changes along the GI tract, three dissolution media with pH 1.2, 7.4 and 6.8 were sequentially
used. FTIR study confirmed that there was no interaction between drug and polymer. Among all the formulations
Losartan potassium micropheres prepared with cellulose acetate in 1:2 ratio shown prolonged release for a period
of 12 hours. The obtained results revealed the capability of the system in delaying drug release for a programmable
period of time and can prevent a sharp increase in the blood pressure during the early morning hours, a time when
the risk of hypertension is the greatest.
Keyword :
: Losartan potassium; Hypertension; Pulsatile;Microspheres; Hydrogel Plug; Solvent evaporation