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Diffusion studies of methotrexate in Carbopol and Poloxamer gels

1998; Elsevier BV; Volume: 160; Issue: 1 Linguagem: Inglês

10.1016/s0378-5173(97)00187-7

1873-3476

G. W. Lu, H.W. Jun,

Pharmaceutical studies and practices

The diffusion properties of methotrexate (MTX) in two hydrogels, Carbopol 934 (Carbopol) and Poloxamer 407 (PF-127), were compared with those in PEG 1500 and white petrolatum ointments in order to evaluate various factors governing the diffusion of MTX in different semisolid vehicles. A new membraneless method, which employed an MTX gel as the donor phase, was used for the measurement of the diffusivity of MTX in the vehicles. The flux of MTX in the hydrogels was at least 20-fold faster than those found in the ointments. The diffusion coefficients (D) of MTX were 3.58 (±0.31)×10−6 cm2/s in the 2% Carbopol gel and 1.03 (±0.01)×10−6 cm2/s in the 25% PF-127 gel at 34°C, despite similar bulk viscosities of the two gels. The activation energies for the diffusion of MTX in the Carbopol and PF-127 gels were 6.13 kcal/mol and 5.56 kcal/mol respectively, which were in the same order of magnitude as the diffusion of the small molecules in water, indicating that microviscosity rather than bulk viscosity of the gel was primarily responsible for the diffusion of MTX in the gels. D values of MTX in the PF-127 gel were significantly accelerated at higher temperatures, despite increased bulk viscosity of the gels due to the reverse thermal gelation property of PF-127. The diffusivity of MTX was the inverse function of polymer concentration, over the range of 20–30% of PF-127 and 1–3% of Carbopol at 34°C. Significant effects of pH and drug concentration on the diffusivity of MTX in the Carbopol gels were observed, while no such effects were found in the PF-127 gels.