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Tiopronin is a glycine derivative with a mercapto group, the chemical name for N-(2 - mercaptopropionyl) - glycine. Tiopronin free reactive thiol group of the side chain in the body play a variety of pharmacological effects, clinical long-term for the treatment of hepatitis, liver damage, and homocystinuria, the addition Tiopronin also by clearing the eye excess of free radicals and inhibit the crystal protein aggregation, early senile cataract with good effect. The traditional eye drops tears Clear fast, and low bioavailability. In contrast, the in situ gel in a solution state after administration Claim medication site undergoes phase transition to form a semi-solid formulation of the non-chemical crosslinking, the perfect fusion of the advantages of the solution was mixed with a gelling agent. To Tiopronin model drug, from start of study drug corneal permeability prepared with a suitable gelling temperature in situ gel, and the gel drug release behavior, the nature of the formulation, selenium cataract Retardation and aqueous humor pharmacokinetics were investigated. The pH value was adjusted to acidic (pH 5.8), and 0.05% sodium bisulfite and EDTA can significantly improve the the tiopronin stability in water. The tiopronin through the cornea in vitro diffusion behavior correspond to zero-order kinetics characteristics, changes in pH within the range of pH 5 to 8 no significant effect on the tiopronin the corneal through. 0.075% water-soluble Azone the tiopronin the apparent permeability coefficient increased 2.03 times further increases the concentration of Azone showed significant corneal irritation. According to the in vivo characteristics of the eye medication, no film dissolution model, the investigated gel dissolution and drug release behavior. The poloxamer gel drug release completely by corrosion control, and both follow the zero-order kinetics. The combined application of sodium hyaluronate, the drug release in dissolution. Release area, the amount of the oscillation frequency and sodium hyaluronate can affect the gel dissolution and drug release. To 22% poloxamer 407 and 6% poloxamer 188 as a substrate, tiopronin Add 0.2% sodium hyaluronate obtained in situ gel having a a suitable gelling temperature and a sustained release effect, corneal apparent with Tiopronin aqueous solution through coefficients were 15.43 cm · s . -1 17.39 cm · s -1 anterior corneal residence time of 130 min and 7 min. The two formulations having good stability, no irritation in vivo, to meet the requirements for ophthalmic preparations. The selenium cataract in rats as a model to study and compare the role of the tiopronin ordinary eye drops and Tiopronin of in situ gel anti-cataract, the results of the high-dose group tiopronin in situ gel and aqueous solution, respectively, so that the incidence of cataracts was delayed 6d 4d, in the high-dose group sulfur the Pronin situ gelation was better than the aqueous solution group. Rabbit eyes continuous sampling techniques to examine the aqueous humor after topical administration pharmacokinetics. In situ gel in aqueous humor drug concentration - the area under the curve (AUC) is 1.59 times the aqueous solution, and the peak concentration (C , max ) increases, the peak time (T max ) delayed peak shape broaden significantly improves the bioavailability of Tiopronin.
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