Abstract:
The purpose of this study was to develop a stable niosomal eye drop containing angiotensin converting enzyme (ACE) inhibitor for lowering intraocular pressure. Three ACE inhibitors i.e., captopril, quinapril and fosinopril (FOS) were used in this study. Their inclusion complexes formation with parent CDs i.e., alphaCD, betaCD and gammaCD were determined. All drugs represented 1:1 stoichiometry inclusion complex with each CD. Of these, FOS/gammaCD complex showed the highest stability constant. Kinetic degradation study confirmed that FOS showed the lowest degradation in the presence of gammaCD. The obtained results of solution- and solid-state characterizations including molecular docking supported the true inclusion complex formation of FOS with gammaCD. Thermal stability of FOS through heating by sonication method was improved in the presence of gammaCD and significantly protected it from the degradation was found by the addition of two antioxidants, EDTA and sodium metabisulfite. In order to further enhance the chemical stability of FOS in aqueous solution, niosomal formulations were developed. The effects of CD, surfactant type and membrane stabilizer/charged inducers on physiochemical and chemical properties of niosome were evaluated. The pH value, average particle size, size distribution and zeta potentials were within the acceptable range. All niosomal formulation showed slightly hypertonic with low viscosity. Span®60/dicetyl phosphate niosomal formulations in the presence and absence of gammaCD were selected as the optimum formulations according to high % entrapment efficiency and negatively zeta potential values as well as in-vitro controlled release profile. The lowest flux and apparent permeability coefficient values of FOS in niosome containing gammaCD in ex-vivo permeation confirmed that FOS/gammaCD complex was encapsulated within the inner aqueous core of niosome and could be protected it from hydrolytic degradation. The stability data revealed that FOS loaded niosomal preparation exhibited good physical and chemical stability especially of that in the presence of gammaCD for at least three months at storage condition of 4ºC.
