Ali Al-Kulabi, Louis Gooden and Ijeoma F. Uchegbu*
Background: Mycophenolic acid (MPA), an immunosuppressive agent, is used orally to reduce corneal graft rejection. However its oral use is associated with gastrointestinal side effects.
Objectives: To prepare MPA nanoparticle eye drops and a validated analytical method.
Methods: Aqueous MPA eye drops were prepared by nanoencapsulation of MPA using Nanomerics MET (N-palamitoylN-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan) at a MET, MPA ratio of 7.5: 1 g g-1 in the presence of glycerol (2.75% w/w). A validated MPA in-formulation drug substance assay was then developed.
Results: MET-MPA formulations were prepared as well as a validated assay. Assay validation parameters for the analysis of MPA in the formulation were satisfactory [Plate count = 16458, Capacity Factor = 2.4, Tailing Factor = 1.02, linearity = 0.999 (0.016 – 0.5 mg mL-1 ), limit of detection = 0.056 mg mL-1 , limit of quantification = 0.17 mg mL-1 , accuracy = 98%, intraday and interday relative standard deviation = 0.45% and 4% respectively]. The candidate formulation (z - average mean = 66 ± 0.4 nm, polydispersity index = 0.12 ± 0.012, drug content = 1.14 ± 0.003 mg mL-1 , zeta potential = +8.5 ± 1.4 mV, pH = 7.4 ± 0.02, osmolarity = 309 ± 1.5 mOSm L-1 , viscosity = 1.04 ± 0.001 mPa.s) was then found to be stable for 14 days with respect to drug content at refrigeration, room and accelerated (40C )temperature and. All other formulation parameters were within the ocular comfort range.
Conclusions: A validated assay (ICH and US FDA guidelines) for new MPA nanoparticle eye drops has been developed.
Eye Drops , Mycophenolic Acid , Liquid Chromatography, Analytical Validation , drug, nanotechnology
UCL School of Pharmacy, 29 – 39 Brunswick Square, London WC1N 1AX, UCL School of Pharmacy, 29 – 39 Brunswick Square, London WC1N 1AX, UCL School of Pharmacy, 29 – 39 Brunswick Square, London WC1N 1AX