Pharmacokinetic studies for the development of transdermal drug delivery systems

PhDThis thesis mainly describes a series of Phase I pharmacokinetic studies conducted on the TDS®d elivery systemw hich combinedw ith lidocaine,t estosteronea, nd a new drug, Melanotan-I for the transdermal drug delivery. Pharmacodynamic studies have also been carried out in certain areas to support the pharmacokinetics. The initial challenge was the development and validation of a method to analyse lidocaine in human plasma by LCMS-MS. The sensitivity and reliability of the developed method has enabled the analysis of lidocaine plasma levels from the TDS®- Lidocaine study. The results from the study have shown that the TDS® system has been able to deliver the drug effectively through the skin. This finding had a positive impact on the future development of the TDS® system in combination with other drugs. The combination of the TDS® system with testosterone had been successfully tested in 12 healthy male subjects. TDS®-Testosterone was found to be bioequivalent to Androgel®. This result gave an insight into further development of this preparation if it is to be regarded as an alternative treatment for hypogonadism. Various methods of correcting for endogenous testosterone were performed on the data and the influence on bioequivalence was studied. Testosterone was used as a model drug and used to explore potential guidelines for the bioequivalence assessment of endogenous compounds. Finally, the TDS® system has been combined with a new, peptide derived drug, Melanotan-I (MT-I). This drug is currently under development for the cosmetic purposes and the treatment of various skin conditions related to sun allergies. A dose escalation study of TDS®-Melanotan for the protective tanning of skin was carried out and the result was presented. In addition, in vivo techniques, such as microdialysis and tape stripping, have also been explored to investigate the feasibility of measuring pharmacokinetic of a transdermal drug instead of using the conventional systemic measurements

THE EFFECT OF FRAGMENTATION ON THE ENGINEERING PROPERTIES OF GRANULAR MATERIALS; LABORATORY AND FRACTAL ANALYSES

Granular materials forming part of engineering structures such as rockfill dams, embankments, the base of flexible pavements and foundations are constantly subjected to harsh environmental conditions and external forces including static and dynamic loads. As a result, these materials experience various levels of fragmentation. In this study, the levels of fragmentation were analyzed from particle/grain size distribution (PSD) plots before and after fragmentation as well as the fractal dimension concept from fractal theory. The fractal dimension concept was found to evaluate well the fragmentation induced in specimens of sands, gravels and glass beads.Tests on abrasion as a result of peripheral fragmentation of gravels (5.5 mm.) were produced in the laboratory using the Jar mill apparatus. Applying the area-perimeter method of fractal analysis, it was found that as the profile of the particles becomes more rounded the fractal dimension reduces in value.Total fragmentation and crushing of granular specimens induced in test apparatus such as the Bromhead Ring Shear, Universal Testing machine and Standard Proctor produces the PSD that evolves from a uniform to a well-graded condition. As a result, the fragmentation fractal dimension increases.Changes in the engineering properties such as the elastic moduli, hydraulic conductivity and the shear strength were also studied. Tests on the elastic moduli of the fragmented gravels using an ultrasonic velocity Pundit apparatus indicated an increase in the elastic moduli as the levels of fragmentation were increased. Hydraulic conductivity tests indicated that the permeability of the samples decreased as the levels of fragmentation increased. Shearing of Quartz sand (1.6 mm.) in the Ring Shear apparatus indicated a decrease in the angle of internal friction as the fragmentation was increased.An investigation on the angle of repose of binary mixtures of coarse and fine materials on a smooth glass base as compared to that on rough surface porous stone base was also conducted. A theoretical relationship between the angle of repose, the angle of internal friction and the interface basal friction was developed. It was found that the different compositions of the binary mixture and the basal friction significantly influenced the angle of repose

Impact of Education Status, Religious Knowledge and Family Economy on the Practicing Prayer Students for Primary School in Setiu District, Terengganu Malaysia

Prayer is a religious pillar where prayer is the greatest of worship that brings the servant closer to his Lord and it is the steadfastness of the relationship of the creature and its creator. The sholat according to syarak is defined as a few words and deeds commenced with takbir and endorsed with greetings and with the conditions specified. This study was conducted to determine the effectiveness of educational status, religious knowledge and family economy on student prayer practice primary school in Setiu District. Total sample 175 secondary school students (level two) of the study. Data were analyzed using IBM-SPSS-AMOS (SEM) program version 21.0. The findings indicate that the educational status, religious knowledge, and family economy on student prayer practice primary school. Furthermore, Inference analysis findings also show educational status, religious knowledge and family economy, have a positive and significant influence on student prayer practice. This shows that family education, especially in religious knowledge and economic family, plays a role in the practice of prayer in primary schools. In conclusion, the implications of this research, the researchers are aware of the need for cooperation from the school to emphasize the students on the practice of prayer in their daily lives. Although the level of education and family economics is a factor in the practice of prayer in this study, the role of teachers helps to overcome them. DOI: https://doi.org/10.5281/zenodo.3467647 &nbsp

Prediction of Landslides Using Surface Wave Analysis Incorporating with GIS: A Case Study in Selangor, Malaysia

Sites Bukit Antarabangsa, Selangor and at Universiti Kebangsaan Malaysia, Selangor were investigated using Multichannel Analysis of Surface Wave (MASW) method. Surface wave method is incorporated with Geographic Information System (GIS) to investigate the hazardous zone for landslides that allows online data to obtain near surface soil profiles. Low frequency seismic signals are used to get 2-D tomography profiles of surface soil near landslides. It is possible to identify landslide risks, if geological and geotechnical properties of soil are known. The effects of different man-made factors for landslides are characteristic properties of soil, slope geometry, road construction etc. The results of analysis of soil properties within the areas are presented in this paper. The GIS interfacing with seismic sensors is capable of showing the shear wave velocity, Vs and shear modulus Gs of risk areas through online seismic records. The aim of this paper is to obtain the online records of risk areas for landslides by getting the soil properties of surface soil using MASW

CONSTRUCTION OF A NEW HIGHWAY EMBANKMENT ON THE SOFT CLAY SOIL TREATMENT BY STONE COLUMNS IN MALAYSIA

To continue of the second phase of the East Coast Expressway between Kuantan and Kula Terengganu in Malaysia system innovative solution are required. In this new phase there are embankment region has been subjected to extensive soft clay soil. These comprise typically of clayey silts of very high water content and undrained shear strengths in the range of 8 to 11 kPa to depths of up to 8m. To support an embankment height of up to 12 m, were filled and thereafter Vibro Replacement treatment was carried out to treat the very soft soil. Extensive instrumentation using rod settlement gauges, inclinometers and piezometers were installed to monitor the performance of the Vibro Replacement treatment. This paper reports on aspects of design, installation and the measured results from the instrumentation scheme

Coupled CWT Spectrogram Analysis and Filtration: New Approach for Surface Wave Analysis (A Case Study on Soft Clay Site)

Surface wave analysis consists of generation, measurement and processing of the dispersive Rayleigh waves recorded from two or more vertical transducers. However, in case of soft clay soil, the reliable dispersion curve is difficult to be produced particularly at the frequency below 20 Hz. Some noises from nature and other human-made sources may disturb the generated surface wave data. In this paper, coupled analysis of continuous wavelet transform (CWT) spectrogram analysis based on Gaussian Derivative function was used to analyze the seismic waves in different frequency and time. First analysis is time-frequency wavelet spectrogram which was employed to localize the interested seismic response spectrum of generated surface waves. Second analysis is a time-frequency wavelet filtering approach which was used to remove noisy distortions in the spectrogram. Based on the generated spectrogram, the thresholds for wavelet filtering could be easily obtained. Consequently, the denoised signals of the seismic surface waves were able to be reconstructed by inverse wavelet transform considering the thresholds of the interested spectrum. Results showed that the CWT spectrogram analysis is able to determine and identify reliable surface wave spectrum and phase velocity dispersion curve of soft clay residual soil. This technique can be applied to problems related to non-stationary seismic wave

Geotechnical Behaviour of a Malaysian Residual Granite Soil

Granite soil is widely distributed in Peninsular Malaysia. Steep terrain, heavy seasonal rainfall and deep tropical weathering are the main causes of numerous slope failures in this formation. Information on the shear strength of soil and its behaviour is essential for safe and economic design geotechnical structures. In order to study the fundamental behaviour of this residual soil, direct shear tests were conducted on remoulded and undisturbed specimens. The soil was subjected to soaked and unsoaked conditions to study the effects of wetting. In addition, triaxial CD and C tests were also conducted. The behaviour in direct and triaxial shear did not indicate peak strength in the stress-strain plots in all specimens. In direct shear tests, significant volume change behaviour was observed between unsoaked and soaked specimens. The shear strengths of soaked specimens were significantly lower than that of unsoaked specimens. Thus the effects of wetting is very obvious. In triaxial tests, the strength parameters (c', tP') for CD and CD tests were not found similar. All important observations are highligted in the paper

Preparation of residual soil samples by using modified method

The purpose of this study was to establish an alternative method in preparing the residual soil samples for laboratory tests. The soil was compacted by using the modified method in order to get the desired values of dry unit weight that was equivalent to the values obtained from standard compaction method. The advantage of using this method was that, due to its larger size, more samples could be taken and tested under the same compaction condition and the mould could be directly mounted on the shaking table with the addition of the air bags to avoid the occurrence of boundary effects. The soil was compacted in a 300mm x 300mm x 300mm mould by using the vibrating hammer. The results of this study showed that the average dry unit weight value of 13.4 kN/m3, 13.6 kN/m3 and 13.7 kN/m3 obtained from 5 rounds/layer, 6 rounds/layer and 7 rounds/layer of compaction of modified method, was equivalent to about 92%, 93 % and 94% of maximum dry unit weight obtained from standard compaction method, respectively