Transdermal Nicotine Delivery Systems: Multi-institutional Cooperative Bioequivalence Studies

Abstract

Nicotine transdermal delivery systems (nicotine-TDSs) have been evaluated clinically and found to provide effective assistance to smokers in smoking cessation with minimal occurrence of withdrawal symptoms. However, substantial skin reactions have been reported with the four nicotine-TDSs marketed recently. To reduce the skin reactions, a new type of nicotine-TDS has been recently developed. In vitro skin permeation studies demonstrated that this nicotine-TDS yields a constant skin permeation profile with a rate of permeation across the human cadaver skin comparable to the steady-state permeation rates attained by Habitrol? and Nicoderm® systems. Clinical studies completed in two ethnic groups have demonstrated that this newly-developed nicotine-TDS is clinically effective and has yielded minimal skin irritation. As part of technical transfer program, a clinical study was initiated in 18 non-obese non-smoking Taiwanese, using Latin-square design, to compare the systemic bioavailability and pharmacokinetic profile of nicotine delivered transdermally from the nicotine-TDSs fabricated at technology licensee (Sintong nicotine-TDS) in comparison with that from the technology developer (TBS nicotine-TDS), using one marketed nicotine-TDS (Habitrol? system) as the reference product. In vitro release and skin permeation studies of nicotine from the nicotine-TDSs manufactured at both licensor and licensee were found similar in kinetic profiles and comparable in rates. Since the patch size of these nicotine-TDSs studied was smaller than the marketed product used (10 cm² for both Sintong and TBS nicotine-TDSs, versus 20 cm² for Habitrol? system), the daily doses of nicotine delivered to the volunteers are equivalent between Sintong and TBS nicotine-TDSs [9.58 (± 2.23) vs. 8.76 (± 1.88) mg/day/patch] but are lower than that from Habitrol? system [15.13 (± 4.05) mg/day/patch]. Thus, for the statistical analysis of the pharmacokinetic parameters obtained need to be corrected for the difference in patch size and daily nicotine dose delivered. The results of statistical analysis suggested that Sintong and TBS nicotine-TDSs are bioequivalent to Habitrol? system.     

Transdermal Nicotine Delivery Systems: Multi-institutional Cooperative Bioequivalence Studies

Nicotine transdermal delivery systems (nicotine-TDSs) have been evaluated clinically and found to provide effective assistance to smokers in smoking cessation with minimal occurrence of withdrawal symptoms. However, substantial skin reactions have been reported with the four nicotine-TDSs marketed recently. To reduce the skin reactions, a new type of nicotine-TDS has been recently developed. In vitro skin permeation studies demonstrated that this nicotine-TDS yields a constant skin permeation profile with a rate of permeation across the human cadaver skin comparable to the steady-state permeation rates attained by Habitrol™ and Nicoderm® systems. Clinical studies completed in two ethnic groups have demonstrated that this newly-developed nicotine-TDS is clinically effective and has yielded minimal skin irritation. As part of technical transfer program, a clinical study was initiated in 18 non-obese non-smoking Taiwanese, using Latin-square design, to compare the systemic bioavailability and pharmacokinetic profile of nicotine delivered transdermally from the nicotine-TDSs fabricated at technology licensee (Sintong nicotine-TDS) in comparison with that from the technology developer (TBS nicotine-TDS), using one marketed nicotine-TDS (Habitrol™ system) as the reference product. In vitro release and skin permeation studies of nicotine from the nicotine-TDSs manufactured at both licensor and licensee were found similar in kinetic profiles and comparable in rates. Since the patch size of these nicotine-TDSs studied was smaller than the marketed product used (10 cm² for both Sintong and TBS nicotine-TDSs, versus 20 cm² for Habitrol™ system), the daily doses of nicotine delivered to the volunteers are equivalent between Sintong and TBS nicotine-TDSs [9.58 (± 2.23) vs. 8.76 (± 1.88) mg/day/patch] but are lower than that from Habitrol™ system [15.13 (± 4.05) mg/day/patch]. Thus, for the statistical analysis of the pharmacokinetic parameters obtained need to be corrected for the difference in patch size and daily nicotine dose delivered. The results of statistical analysis suggested that Sintong and TBS nicotine-TDSs are bioequivalent to Habitrol™ system.     

Optimal Estimation of the Acceleration of a Car Under Performance Tests

In this paper, a recursive least-squares lattice (RLSL) adaptive filter was used to carry out the optimal estimation of the relevant signal coming from an accelerometer placed in car under performance tests. Here, the signal of interest is buried in a broadband noise background where we have little knowledge of the noise characteristics. In addition, due to the fact that the noise and the relevant information sometimes share the same or a very similar frequency spectrum, it is very difficult to cancel the noise that corrupts the relevant information without causing that information to deteriorate. The results of the experiment are satisfactory and, in order to compare classical filtering with optimal adaptive filtering, the signal coming from the accelerometer was also filtered by using a third-order lowpass digital Butterworth filter. The results of comparing the aforementioned filters show that the optimal adaptive filter is superior to the classical filter. Here, a significant improvement of 22.4 dB in the signal-to-noise ratio (SNR) at the RLSL adaptive filter output was achieved. However, the improvement in the SNR at the Butterworth filter output was 6.1 dB, which shows very clear that the optimal adaptive filter performs much better than the classical one     

删失数据下一类回归模型的参数估计

考虑一类回归模型,在右删失数据下构造了参数的最小二乘估计和加权最小二乘估计,证明了估计量具有渐近正态性。模拟结果表明加权最小二乘估计比最小二乘估计有优良的性质。     

删失数据下密度核估计的误差分布的强逼近

在随机右删失数据下构造了概率密度函数的核估计和随机加权估计,得到了核估计的误差分布的正态逼近速度和随机加权逼近速度,改进了孙六权和朱力行(1999)的主要结果。     

Best Linear Invariant Estimation for Weibull Parameters Under Progressive Censoring

Best linear invariant estimators of log reliable life are derived for a model in which failure times have a two-parameter Weibull distribution and removal of some surviving items from life test is allowed at the time of any failure. Weights for obtaining best linear invariant estimates under this model are given in tabular form for all censoring patterns for sample sizes 2 through 6.     

MHSS压缩有效力学性能研究

金属空心球结构(Metallic hollow sphere structure,MHSS)是一种新型的超轻多孔金属材料。利用ANSYS有限元分析软件模拟了薄壁金属空心球的压缩过程,采用非线性和瞬态分析方法得出了其名义应力-应变曲线,与实验曲线进行对比分析发现两条曲线较为吻合。对3种不同堆积模式的金属空心球结构进行了压缩数值模拟分析,得出了其压缩的有效屈服极限和有效弹性模量等力学性能。通过研究材料中单球的受力状态,分析了不同堆积模式材料力学性能出现差异的原因,其理论预测结果与数值模拟结果具有相同的规律。     

Parameter Estimation Employing a Dual-Channel Sine-Wave Model Under a Gaussian Assumption

The CramÉr–Rao bound (CRB) is a lower bound on the error variance of any estimator. For a Gaussian scenario, the CRB is derived for a seven-parameter, dual-channel sine-wave model, which is a model relevant to applications such as impedance measurements and the estimation of particle size and velocity by laser anemometry. Four different parameterizations were considered: the common quadrature/in-phase and amplitude–phase models and two relative amplitude–phase models. The CRB indicated the achievable error variance of an unbiased estimator as a function of the signal-to-noise ratio (SNR), the number of samples, and noise power. A nonlinear least squares fit of the signal model to the collected data was employed. The problem at hand is separable and can be solved by a 1-D search followed by a linear least squares fit of the remaining parameters. The performance of the method was investigated with the aid of a simulation study, and the outcome was compared with that of the corresponding CRB and with a recently proposed seven-parameter fit. For high SNRs, the performance of the proposed method is close to optimal with an error variance close to the predictions made by the CRB.      

The Application of Multiresponse Estimation to Drug Stability Studies

This paper focuses on the statistical methodology for the simultaneous analysis of stability data obtained on both parent compound and degradation products. A mathematical model based on kinetic theory is developed to describe both the disappearance of parent compound and appearance of degradation products. Analysis of data obtained from accelerated testing of drug stability is accomplished by extending the kinetic model to include the Arrhenius relationship. A simulated data set generated from parameter estimates obtained from an actual analysis is used as an example to illustrate the statistical techniques.     

Numerical Estimation of Plastic J-Integral by the Load Separation Method for Inclined Cracks Under Tension

The load separation concept is employed to determine the mixed mode plastic η _pl and h^COD_pl{\eta^{COD}_{pl}} factors for the tension plate with an inclined centre throughthickness crack for power law hardening materials. The separation parameters S _ij are calculated from the FE computed load – plastic displacement (or COD) curves for each case. It is shown that the mixed mode plastic η _pl factor is a function of both the crack angle orientation θ (or the applied elastic parameter M _e ) and the strain hardening exponent.     

The Application of Multiresponse Estimation to Drug Stability Studies

Abstract

This paper focuses on the statistical methodology for the simultaneous analysis of stability data obtained on both parent compound and degradation products. A mathematical model based on kinetic theory is developed to describe both the disappearance of parent compound and appearance of degradation products. Analysis of data obtained from accelerated testing of drug stability is accomplished by extending the kinetic model to include the Arrhenius relationship. A simulated data set generated from parameter estimates obtained from an actual analysis is used as an example to illustrate the statistical techniques.     

Constant Stress Accelerated Life Test: Different Methods of Estimation Under the Exponentiated Power Lindley Distribution

Strength of Materials - Accelerated life testing has been used frequently in several fields as it provides an economical way for obtaining failure time data rapidly or in a shorter time as compared...     

有色观测噪声背景下正弦信号参量估计的互谱Levinson方法

本文从理论上证明了互相关函数的Yule-Walker方程，并在此基础上提出了互谱AR模型参数估计的Levinson递推自满，该自满可有效地克服传统互谱估计的FFT方法和周期图法存在的谱分辩率低、谱估计方差大等缺点，仿真试验表明，该方法还可有效的克服有色观测噪声对测量精度的影响。