Chuei Wuei Leong

The current study aimed to evaluate the bioequivalence of a new generic combination of simvastatin and ezetimibe with the reference formulation. An open-label, randomized, 3-period, 3-sequence, crossover study, including 60 healthy volunteers, was implemented. Participants received the test and reference formulation, each containing 20 mg of simvastatin and 10 mg of ezetimibe as a single-dose tablet, separated by a minimum of 2-week washout periods. Blood samples were collected for 20 time points from predose to 72 hours after the dose. The total ezetimibe assay was carried out using a validated liquid chromatography-tandem mass spectrometry, while unconjugated ezetimibe, simvastatin, and simvastatin beta-hydroxy acid determination was done via a validated ultra-performance liquid chromatography-tandem mass spectrometry. Each assay was preceded by a liquid-liquid extraction step. The pharmacokinetic parameters were derived using noncompartmental analysis and then compared between the reference and test formulations via a multivariate analysis of variance. No statistical difference was found in under the concentration-time curve from time 0 to the last quantifiable concentration and maximum concentration of unconjugated ezetimibe, total ezetimibe, and simvastatin between the reference and test formulations. The 90% confidence intervals of unconjugated ezetimibe, total ezetimibe, and simvastatin natural log-transformed under the concentration-time curve from time 0 to the last quantifiable concentration, and maximum concentration were in the range of 80%-125% as per the bioequivalence acceptance criteria. Therefore, the test formulation was bioequivalent to the reference formulation.

The present study aimed to assess the bioequivalence of a new apixaban generic with reference formulation. Twenty-six healthy volunteers were recruited for an open-label, balanced, randomized, 2-treatment, 2-sequence, 2-period, single oral dose study. Following overnight fasting, each volunteer received 5 mg of apixaban test and reference formulations as single doses, separated by a 1-week washout period. Twenty blood samples were collected at predose and multiple time points between 0.5 and 72 hours after dosing. A validated ultra-performance liquid chromatography-tandem mass spectrometry detection method following a protein precipitation step was implemented to determine apixaban concentrations. Noncompartmental analysis was used to derive the pharmacokinetic parameters, which were then compared between the test and reference products using a multivariate analysis of variance. The pharmacokinetic parameters of the test product were not statistically different from the reference product, and the 90% confidence intervals of apixaban natural log-transformed area under the concentration-time curve from time 0 to infinity, area under the concentration-time curve from time 0 to the last measurable concentration, and maximum concentration were within 80%-125% based on the bioequivalence acceptance range criteria. The test and reference formulations of apixaban are bioequivalent in healthy subjects under fasting conditions.

A newly developed branded generic of a moxifloxacin (MOX) 400‐mg tablet formulation was manufactured prior to this study. A bioequivalence (BE) study was done to assess the pharmacokinetics of the formulation using a randomized, open‐label, 2‐period crossover, 2‐sequence, and single‐dose experiment. Thirty healthy male volunteers were recruited. The test formulation, Flonoxin 400 mg, was compared with the reference formulation, Avelox 400 mg. The pharmacokinetic parameters of MOX were calculated based on the plasma drug concentration‐time profile. Noncompartmental analysis was performed to determine its safety and tolerability. The 90% confidence intervals (CIs) were 88.5%‐104.6%, 96.1%‐101.1%, and 96.8%‐100.7% for C_max, AUC_0‐t, and AUC_0‐inf, respectively. All CIs were within the 80.0%‐125.0% boundary, thus fulfilling the acceptable BE criteria according to the ASEAN guidelines.

To evaluate the safety of two new generic ophthalmic formulations, Latanost^® (latanoprost) and Latacom^® (latanoprost and timolol) by utilizing the three-dimensional reconstructed human cornea-like epithelium (RhCE) tissue constructs as an in vitro model in the assessment of ocular irritation. In vitro irritation test was conducted on Latanost^® (LTN) and Latacom^® (LTC) and their corresponding innovators, Xalatan^® (XLT) and Xalacom^® (XLC), respectively, by using RhCE. According to the OECD guidelines No. 492 on the testing of chemicals, the ophthalmic formulations were assessed via topical exposure of the formulations on in vitro RhCE tissue. Cell viability was measured by MTT assay. The mean cell viability percentage of LTN and XLT was 70.5 and 75.7%, respectively, whereas, for LTC and XLC, the percentage viability was 95.3 and 85.7%, respectively. The two new generic formulations (LTN and LTC) did not reduce the cell viability of the RhCE tissue to ≤60%. Thus, both can be considered as nonirritant. Both newly developed generics are nonocular irritants. This study informs the safety assessment of new generic antiglaucoma ophthalmic solutions applicable for long-term glaucoma treatment. The formulations aim to keep eye irritation to a minimum level. Ng JSC, Tan YX, Alwi NAA, et al. In Vitro Toxicity Evaluation of New Generic Latanost^® and Latacom^® as an Ophthalmic Formulation. J Curr Glaucoma Pract 2021;15(3):139-143.