TRANEXAMIC ACID LIPOSOMES 379 DETERMINATION OF TA CONTENT The calibration graph of TA solution in DI water was demonstrated to be linear (r 2 = 0.9937), over the concentration range 4.0-20.0 lag/mi. The regression equation was as follows: y = 20.7903 x - 0.1942, where y is the concentration of TA (lag/ml) and x is the absorbance of the derivative of TA formed with 2,4,6-trinitrobenzosulfonic acid (mAU*s). The recoveries of TA from liposome formulations using spectrophotometric assay varied between 91.4% and 104.7%. The other components in liposome formula- tions neither reacted with the color reagent nor exhibited significant absorption at 415 nm. STABILITY OF LIPOSOMES The physical appearances of the 7:2:1 (5% TA,+), 7:2:1 (10% TA,+), 7:2:1 (5% TA,-), and 7:2:1 (10% TA,-) liposomes, either freshly prepared or stored at 4 ø, 30 ø, and 45 ø (+ iø)C for 90 days are shown in Table II. The physical notation of deterioration of liposome formulations, especially the positively charged liposome, can be observed from an increase in the turbidity of supernatant following storage at 30 ø and 45øC for 90 days (Table II). The amount of the remaining TA entrapped in various liposome formulations during storage at 4 ø, 30 ø, and 45øC for 90 days (Table III, Figure 1) was analyzed, using the proposed models (Table I), to estimate the leakage rate constant and shelf life of entrapped TA in liposomes (Table IV). The predicted shelf lives of TA in all liposome formulations varied between 19.0 and 65.1 days, with the longest shelf life observed in the 7:2:1 (10% TA,-) liposome (Table IV). The degradation rate constants of total TA in liposomes, and in the pellet of liposome formulations, estimated using the first-order equation, are presented in Table V. The degradation rate constants of total TA in all liposome formulations (0.0002-0.0016 d -•) were about four to nine times lower than those in the pellet of liposomes (0.0018-0.0069 d -•, Table V). DRUG RELEASE The cumulative percentages of the amount of TA released from various liposome for- mulations, 5% and 10% TA solutions in DI water during 24 hours at 37øC, are presented in Figure 1. The experimental data obtained were analyzed using the Higuchi model (Table I) to estimate the release rate constant of TA from liposomes (Table VI). The cumulative percentages of TA released from the positive and negative liposomes with the same drug concentration were not significantly different (Figure 2). However, high TA concentration in the liposomes appeared to exhibit a higher release rate con- stant of TA (Figure 1, Table VI). The total amount of TA released from liposome formulations during 24 h varied between 28.0% and 37.9%, with the highest amount observed in the 7:2:1 (10% TA,-) liposome (Table VI). DISCUSSION All liposome formulations appeared to be colloidal systems, either freshly prepared or stored at 4 ø, 30 ø, and 45øC for 90 days (Table II). No sedimentation and flocculation

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