http://etd.aau.edu.et:80/dspace/handle/123456789/440 Search the Channel search http://etd.aau.edu.et:80/dspace/simple-search http://etd.aau.edu.et:80/dspace/handle/123456789/3137 Title: STRESS DECOMPOSITION STUDIES AND DEVELOPMENT OF VALIDATED STABILITY INDICATING HPLC ASSAY METHOD FOR LAMIVUDINE <br/> <br/>Authors: Berrhanue Muche <br/> <br/>Abstract: Lamivudine belongs to the class of nucleoside reverse transcriptase inhibitors, and is potent in vitro and in vivo inhibitors of human immunodeficiency virus (HIV), which is the causative agent of the acquired immunodeficiency syndrome. Various analytical methods have been reported for the determination of lamivudine in the biological fluid such as plasma, CSF, saliva and urine. They have been used to support pharmacokinetic study. However, there are no reported stability-indicating HPLC assay methods for this drug. Though reported methods are highly specific and sensitive for this drug they may not yield precise and accurate result for determination of the API in the presences of its degradation product. Stability requirements for the world wide registrations of pharmaceutical products have undergone a dramatic change in the past few years with the advent of ICH guidelines. ICH has introduced a standardized approach for the development of stability data for registration through various guidelines. Therefore, it is necessary to develop a stability indicating method for these drugs to ensure the safety, quality and efficacy of these drugs. The aim of the present study is thus to establish the inherent stability of lamivudine, a nucleoside reverse transcriptase inhibitor, through stress studies under a variety of ICH recommended test conditions and develop validated stability indicating assay method. In this study all solution was prepared and used according to USP 24 and BP 1999 and forced decomposition studies were conduct to generate degradation products of the API following the condition recommended by the ICH guideline Q1A. The stressed samples obtained were subjected to preliminary analyses by employing HPLC to study the number and types of degradation products formed under various conditions. The result of this study showed that the drug was liable to degradation in all stressed condition though the extent of degradation varied. The API was found to be more liable to decompositions in alkaline solution than in acidic solution and neutral condition. Degradation of lamivudine in neutral solution was observed relatively after long hour of refluxing indicating that the drug is relatively stable in neutral condition. Relative rate of degradation of the drug in hydrolytic and oxidative condition shows that the rate of hydrolytic degradation in xiii acidic solution (0.1N HCl) was less than the rate of oxidative degradation in hydrogen peroxide (3.0%). Separation of the drug and the degradation products under various conditions was successfully achieved on C-8 column by using a mobile phase composed of 0.1M ammonium acetate: methanol: 1 %(v/v) acetic acid in the ratio of 91.9:8:0.1. The method was validated with respect to linearity, precision, accuracy, selectivity, specificity and ruggedness. The response was linear (r=0.9998) in the drug concentration range of 5-500 μgml-1. The mean values (±RSD) of slope and intercept were 46376 (±0.006975) and 200049 (±0.4009) respectively. The RSD values for intra–and inter-day precision studies were <0.292 %and <1.781% respectively. The recovery of the drug ranged between 98.3 - 101.16% from the mixture of degradation products. The method was specific to the drug and also selective to degradation products. The developed method is simple accurate, precise, specific and selective and rugged and thus it can be used for analysis of the drug and its degradation products. http://etd.aau.edu.et:80/dspace/handle/123456789/1950 Title: SYNTHESIS AND ANTIMICROBIAL TESTING OF TRIPHENYLTINSALICYLATEPYRIDINE <br/> <br/>Authors: WALELIGN, FIKADU <br/> <br/>Abstract: Synthetic, spectroscopic and biological studies of triphenyltinsalicylate pyridine (TPhTSaPy) complex derived from pyridine having a nitrogen donor system have been undertaken. Silversalicylate, on interaction with triphenyltin chloride (TPhTCl), yielded triphenyltinsalicylate (TPhTSa), which upon further interaction of the intermediate (TPhTSa) with pyridine afforded the TPhTSaPy complex having a Sn N bond. The structures of these compounds were elucidated by elemental analysis and spectroscopic (IR, Mass, 1H and 13C NMR) studies. The growth-inhibiting potential of the final product (TPhTSaPy) and its intermediate (TPhTSa) was compared with that of the commercially available antifungal drug TPhTCl against a series of medically important pathogens including fungal, and Gram-positive and Gram-negative bacterial strains. The results revealed that TPhTSaPy was strongly active against Staphylococcus aureus 29737, S. aureus ML 267, Escherichia coli RP4, Pseudomonas aeruginosa ATCC 25619 and Vibrio cholerae 2 while it failed to exhibit any activity against Sarcina luteus 9341, Bacillus subtilis ATCC 6633 and B. pumilus 8241 at the tested concentrations. TPhTSaPy displayed moderate activity against E. coli K88, E. coli ATCC 10536, E. coli VC Sonawave 3:37 C, E. coli 18/9, E. coli CD/99/1, Shigella dysentery 1, S. dysentery 8, S. soneii 1, S. soneii BCH 397, S. boydii 937 and S. flexneri Type 6, V. cholerae 1037 and V. cholerae 785. The lowest MIC (25 μg/ml) value was observed against S. aureus 29737, S. aureus ML 267, E. coli RP4, P. aeruginosa ATCC 25619 and V. cholerae 2. TPhTCl was active against E. coli and V. cholerae 2. But, S. luteus 9341, B. pumilus 8241 and B. subtilis ATCC 6633 strains were completely resistant to it. On the other strains of bacteria it showed moderate activity. The lowest MIC (25 μg/ml) value was observed against E. coli CD/99/1, E. coli 18/9, E. coli K88 and V. cholerae 2. According to these results, TPhTSaPy was more active than TPhTCl against S. aureus, and P. aeruginosa but less active against E. coli. Thus, TPhTSaPy has shown a broad antibacterial spectrum than TPhTCl. But, the activity of TPhTCl against the fungal strains tested in the present study namely, Candida albicans ATCC 10231, Aspergillus niger ATCC 6275, Penicillium notatum ATCC 11625 and P. funiculosum NCTC 287 was superior to that of TPhTSaPy. <br/> <br/>Description: A thesis submitted to the School Of Graduate Studies Of Addis Ababa University in partial fulfillment of the requirement for the Degree of Master of Science in Pharmaceutical Analysis and Quality Assurances. http://etd.aau.edu.et:80/dspace/handle/123456789/1941 Title: CHEMOMETRICS ASSISTED UV- SPECTROPHOTOMETRIC DETERMINATION OF TOPICAL BINARY MIXTURES CONTAINING BENZOIC ACID, SALICYLIC ACID OR RESORCINOL <br/> <br/>Authors: Mulualem, Kassa <br/> <br/>Abstract: Chemometrics-assisted spectrophotometric methods were developed for simultaneous determinations of binary mixtures of (1). benzoic acid and salicylic acid, and (2). resorcinol and salicylic acid mixture. The commercial forms were marketed in Ethiopia and Egypt, such as whitefield ointment, luna soap, and dorin emulsion. The uv absorption spectra of the studied compounds in the range of 200-400 nm, showed considerable degrees of spectral overlapping (between 87.6% for benzoic acid and salicylic acid mixture, and 96.2% for salicylic acid and resorcinol mixture). The resolution of the mixtures have been successfully accomplished by using four techniques namely,1D (first derivative), 1D ratio, CLS (classical least square) and PCR (principal component regression). Variable results were obtained in the different cases as explained in the core of this thesis. Validation parameters such as calibration range, LOD, LOQ, precision and accuracy parameters (Between F- and t-values respectively) were calculated and a comparison between all the methods and some official methods were done. The results showed that the PCR technique was the most suitable for analysis of such binary mixtures or the commercial formulations, more than the other techniques and agrees well with those results obtained from the official method. <br/> <br/>Description: A thesis Submitted to the School of Graduate Studies of Addis Ababa University in partial fulfilment of the requirement for the Degree of Master of Science in Pharmaceutical Analysis and Quality Assurance http://etd.aau.edu.et:80/dspace/handle/123456789/1937 Title: HPTLHPTLC-DENSITOMETRIC DETERMINATION OF SOME WATER SOLUBLE VITAMINS PRESENT IN PHARMACEUTICALS <br/> <br/>Authors: Behailu, Urgessa <br/> <br/>Abstract: A simple, accurate and precise high-performance thin-layer chromatographic (HPTLC) method has been developed for the determination of vitamin B1, B6 and B12 in tablet and injection. Using methanol: ammonium acetate (5M) (10:1; v/v) as mobile phase and HPTLC plates (0.2mm thickness) precoated with 60F254 silica gel on glass plate as stationary phase. Quantification was carried out densitometrically using a UV detector at 255, 290 and 361nm. The retardation factors (Rf) of B1, B6 and B12 were 0.20 ± 0.02, 0.40 ± 0.02 and 0.68 ± 0.02 respectively. Calibration curves were polynomial in the range 250-2050 ng/μl for B1 and B6, 50-1050 ng/μl for B12. The method has been robust for small variation with mobile phase composition, amount of mobile phase and time variation before chromatographic development and scanning. The stability of sample solution was studied over eight hours and no additional spot was observed on the plate. As a result no evidence was observed for the degradation of the product. In addition the proposed method has been compared statistically (t-test and Ftest) with the classical method (HPLC) and there was no difference in terms of accuracy of the dosage analysis between the two methods. The analysis result of both synthetic mixture and pharmaceutical samples showed the quantitative determination of each component accurately in the presence of the other components and back ground interference. Assay of vitamin B1, B6 and B12 were 99.10 ± 1.37 %, 99.68 ± 1.50 % and 99.42 ± 1.26 % for vitamin B1, B6 and B12 injection, 99.44 ± 1.30 % and 99.95 ± 1.49 % for vitamin B1 and B6 tablet respectively. <br/> <br/>Description: A Thesis Presented to the School of Graduate Studies of Addis Ababa University in Partial Fulfillment of the Requirements of the Degree of Master of Science in Pharmaceutical Analysis and Quality Assurance