Formulation and Evaluation of Pulsatile Drug Delivery of Lovastatin

Abstract

In the present study, an attempt was made to develop the pulsatile drug delivery of Lovastatin to reduce plasma cholesterol levels and to prevent cardiovascular diseases. Formaldehyde treated Capsule bodies were used for the preparation of pulsincaps. It was sealed with unhardened cap of the capsule. The microspheres were prepared by emulsion solvent evaporation technique. Hydrogel plug (karaya gum 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. The sealed capsules were completely coated by dip coating method with 5% cellulose acetate phthalate to prevent variable gastric emptying. Optimized microsphere formulations were selected based on dissolution studies. Dissolution studies of pulsatile capsule device in media with different pH (1.2, 7.4 and6.8) showed that drug release in colon could be modulated by optimizing the concentration of polymers in the microspheres. Drug–polymer interaction studies indicated no interaction in between the drug and the polymer. Among all the formulations Lovastatin microspheres prepared with Ethyl cellulose, in 1:3 ratio shown prolonged release for a period of 11 hours. The obtained results showed the capability of the system in delaying drug release for a programmable period of time and to deliver the drug in the early morning hours when cholesterol synthesis are more prevalent.