Lisinopril is an angiotensin converting enzyme inhibitor used in the treatment of hypertension and heart failure in prophylactic treatment after myocardial infarction and in diabetic nephropathy. However, it is very poorly absorbed from gastro-intestinal tract. Intranasal administration is an ideal alternative to the parenteral route for systemic drug delivery. Formulating multiparticulate system with mucoadhesive polymers may provide a significant increase in the nasal residence time. The aim of the present approach was to overcome the drawbacks of the conventional dosage forms of lisinopril by formulating intranasal microspheres with Carbopol 974P NF and HPMC K4 M along with film forming polymer ethyl cellulose.
Methods: The microspheres were prepared by emulsion solvent evaporation method. The prepared microspheres were characterized for encapsulation efficiency, drug loading, particle size, and surface morphology, degree of swelling, ex-vivo mucoadhesion, drug release, ex-vivo diffusion studies. Formulations C4 and H6 displayed the best results for Carbopol and HPMC based microspheres respectively. Entrapment efficiency was 84.95±0.50% and 17.92±0.0.777%; mucoadhesion was 62.66% and 96.33%; and drug release up to 40 minute was 53.66 % and 98.68% for C4 and H6 respectively. Combination of microspheres i.e. HC4 shows drug release upto 98.55%. Ex-vivo studies revealed that the formulations C4, HC4 and H4 showed good bioavailability compared to oral drug administration. Both in-vitro and Ex-vivo studies conclude that combination of Carbopol and HPMC based microspheres are better than single carbopol based microspheres for the delivery of lisinopril.
Keywords: Microspheres, Lisinopril, Solvent evapuoration method.