RESUMO
@#In this study, different functional layer formulations and process parameters were used to prepare the levomilnacipran hydrochloride sustained-release capsules, the influence of functional layer formulation and process factors on dose dumping was studied by comparing their release curves in 40% ethanol; and the risk of dose dumping of the self-developed drug was evaluated by the similar factors of the release curve of the self-developed drug and the reference drug.The results showed that as the coating weight increased, the degree of dose dumping decreased; when the concentration of ethanol in the coating liquid solvent was less than 80%, the dose dumping increased; as the atomization pressure and maturation time increase, the dose dumping became more serious. In 0% ethanol (purified water), 5% ethanol, 20% ethanol and 40% ethanol media, the self-developed and reference preparations had the same degree of dose dumping within the specified time, and rotation speed had no significant effect on the release of metformin in vitro. In summary, formulation factors such as coating weight gain, ethanol concentration in the coating solution solvent, and process factors such as atomization pressure and curing time have a serious impact on the dose dumping of sustained-release capsules.Under the optimal functional layer formulation and process, special attention should be paid to the control of risk of self-developed dose dumping.
RESUMO
OBJECTIVE: To evaluate the pharmacokinetics and bioequivalence of levomilnacipran hydrochloride sustained release capsules in Beagle dogs. METHODS: An open, randomized,two-periods trial design was used. HPLC method was established to determine levomilnacipran hydrochloride in plasma samples of beagle dogs. Pharmacokinetic parameters and bioequivalence were evaluated. RESULTS: The pharmacokinetic parameters of levomilnacipran hydrochloride after oral adminstration of test or reference preparations were as follows: ρmax were (394.06±18.22), (384.88±25.65) ng•mL-1; AUC0-72 h were (5 903.86±107.51), (5 396.63±62.63) ng•h•mL-1; AUC0-∞ were (6 325.90±158.88), (6 091.14±121.35) ng•h•mL-1, respectively. The relative bioavailability of F0-72 h(%) and F0-∞(%) of the test/reference formulation were 109.40%, 103.85%; the 90% CIs for the test/reference ratio of ρmax, AUC0-72 h, and AUC0-∞ were 75.11% to 129.61%, 99.35% to 119.44%, and 89.90% to 117.78%, respectively. CONCLUSION: The RP-HPLC method is simple, efficient and accurate which can be used for the determination of levomilnacipran hydrochloride plasma concentration. The test capsules are bioequivalent to the reference capsules.