DSpace Community: School of Pharmacy

STRESS DECOMPOSITION STUDIES AND DEVELOPMENT OF VALIDATED STABILITY INDICATING HPLC ASSAY METHOD FOR LAMIVUDINE

Tue, 22 May 2012 14:22:17 GMT

Title: STRESS DECOMPOSITION STUDIES AND DEVELOPMENT OF VALIDATED STABILITY INDICATING HPLC ASSAY METHOD FOR LAMIVUDINE

Authors: Berrhanue Muche

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.

GASTROINTESTINAL EFFECTS OF CRUDE KHAT (CATHA EDULIS F) EXTRACT FOLLOWING ACUTE AND SUB-CHRONIC ADMINISTRATION IN RODENTS

Tue, 15 May 2012 08:03:07 GMT

Title: GASTROINTESTINAL EFFECTS OF CRUDE KHAT (CATHA EDULIS F) EXTRACT FOLLOWING ACUTE AND SUB-CHRONIC ADMINISTRATION IN RODENTS

Authors: WINTANA, TADESSE

Abstract: Khat (Catha edulis F) belongs to the Celastraceae family and is a dicotyledonous evergreen shrub/tree used for recreation and alleviation of fatigue in several countries of East Africa and South Arabia. Recently, this habit has spread considerably, raising concern in view of medical and socio-economic consequences of khat consumption. Even though khat has several medicinal, social, and economical values, there are numerous reports regarding its gastrointestinal tract (GIT) adverse effects. As the effects of khat chewing on digestive system mentioned in earlier studies were based on clinical observations, the present study was designed to evaluate the GIT activity of the crude khat extract after acute and sub-chronic administration using different rodent models and parameters used for ulcer and motility measurement were quantified. For acute study, animals were randomly assigned into different groups. Negative control received Tween 80 2% in distilled water, whereas positive controls were given ranitidine (pylorus ligation and cysteamine HCl models), misoprostol (indomethacin induced gastric ulcer), and loperamide (castor oil induced diarrhea and enteropooling assay). The other group received different doses of crude khat extract: 100 mg/kg, 200 mg/kg and 300 mg/kg. For sub-chronic study, one group was administered vehicle and served as control, whilst the other three were administered three doses of khat extract (100, 200, and 300 mg/kg) for 45 days. Acute khat administration in pylorus ligation model was shown to aggravate ulcer compared to controls in the highest dose used, as evidenced by increased volume of gastric acid secretion (p<0.05), total acidity (p<0.05) and ulcer index (p<0.01). Similar results were obtained in indomethacin induced gastric ulcer model where 300 mg/kg khat extract increased mucosal damage as demonstrated by a significant reduction in mucin content compared with misoprostol (p<0.001) and vehicle (p<0.05) treated animals. Khat at 300 mg/kg was also shown to accentuate duodenal ulcer induced by cysteamine HCl by significantly increasing (p<0.01) ulcer area as compared to vehicle-treated rats. Whilst ranitidine was shown to offer antiulcer activity in the models tested, khat at 100 mg/kg was devoid of any significant ameliorating or accentuating effect. Surprisingly, subviii chronic administration of khat at all doses failed to produce neither gastric nor duodenal ulcer. In castor oil induced diarrhea, 300 mg/kg (p<0.001) and 100 mg/kg (p<0.01) khat extracts significantly decreased the number of watery fecal discharge against vehicle treated rats. In addition, 300 mg/kg dose decreased (p<0.05) weight and volume of intestinal content in castor oil induced enteropooling model. In sub-chronic studies, 300 mg/kg and 200 mg/kg khat extracts significantly inhibited intestinal motility in in-vivo gastrointestinal motility model by 53.2% and 48.6%, respectively. On the other hand, weight change on sub-chronic khat extract administration was observed and the change became significant at the 3rd (p<0.05), 4th and 5th week (p<0.01), and 6th week (p<0.001) with 300 mg/kg dose. While in 200 mg/kg decline of weight at 4th week (p<0.05) and for following weeks (p<0.01) was obtained. In conclusion, acute use of khat at higher dose in the presence of ulcerogenic agents could aggravate gastric and duodenal ulcer, while sub-chronic khat administration alone did not produce ulcer. Furthermore, acute and sub-chronic administration of khat extract at higher dose produced a significant constipating activity. And sub-chronic administration of khat extract at higher dose markedly decreased body weight. These effects collectively indicate that khat consumption in large amount and for a longer period of time is associated with adverse GIT outcomes.

STUDIES ON EXTRACTS OF SOME MEDICINAL PLANTS TRADITIONALLY USED FOR DERMATOLOGICAL DISORDERS IN ETHIOPIA

Fri, 11 May 2012 17:21:37 GMT

Title: STUDIES ON EXTRACTS OF SOME MEDICINAL PLANTS TRADITIONALLY USED FOR DERMATOLOGICAL DISORDERS IN ETHIOPIA

Authors: Bruck, Messele

Abstract: The majority of the populations in the developing world rely on traditional medicine for their primary healthcare needs. Herbal therapy predominates in traditional medical practices as well as in complimentary/alternative medicine practiced in the developed world. Among the indications where traditional herbal medicines are used, skin and skin related disorders, which also happen to be common diseases in the communities, rank among the top. This study had the objective of evaluating the extracts of four medicinal plants traditionally used for skin diseases, namely Inula confertiflora, Clematis simensis, Zehneria scabra and Pycnostachys abyssinica, for some of their claimed activities by both in vitro and in vivo methods. The 80 % methanol extract of the dried, ground plant materials was prepared. The plant extracts were then tested for antimicrobial activity against common bacterial and fungal pathogens by the agar well diffusion method. Furthermore, the 80% methanol extract of I. confertiflora was subjected to minimum inhibitory concentration (MIC) determination, in vivo studies such as anti- inflammatory and skin sensitization tests as well as in vitro tests such as preliminary screening for the presence of some plant constituents, TLC analysis, and evaluation of topical antimicrobial formulations of the plant extracts. The results of the study indicated all of the plant extracts to exhibit antimicrobial activities against one of the most common bacterial pathogens, namely Staphylococcus aureus (ATCC). ix Although these activities were not impressive especially as compared to the positive control used, they lend some credibility to the traditional uses of the plants. Good antifungal activity was demonstrated by one of the plant extracts (I. confertiflora) against Trichophyton mentagrophytes, which was further corroborated by the agar dilution method. I. confertiflora (80% methanol) extract proved to exert a good anti-inflammatory activity at a dose of 1000 mg/kg but not at a lower dose (500 mg/ml) in the carrageenan-induced paw edema test. These activities support the traditional use of this plant. Furthermore, the 80% methanol extract of I. confertiflora, was not found to be a skin sensitizer in the mouse ear swelling test as opposed to its petroleum ether counterpart, which demonstrated a strong sensitizing property. Some secondary metabolites such as sesquiterpene lactones and flavonoids were detected, which may be responsible for some of the demonstrated pharmacological activities of this plant. Evaluation of topical formulations of the 80% methanol extract of I. confertiflora demonstrated that the hydrophilic formulations exhibited higher antimicrobial activities compared to the lipophilic formulations. The activity of the hydrophilic formulations against T. mentagrophytes was comparable to the commercially available antifungal products tested. These bases could thus be used as a starting point for further formulation studies.

A PROSPECTIVE STUDY ON SELF-MEDICATION PRACTICES AND CONSUMERS DRUG KNOWLEDGE IN ADDIS ABABA

Fri, 11 May 2012 16:52:58 GMT

Title: A PROSPECTIVE STUDY ON SELF-MEDICATION PRACTICES AND CONSUMERS DRUG KNOWLEDGE IN ADDIS ABABA

Authors: Tenaw, Andualem Tadege

Abstract: Background: Health and disease exist in a continuum. Self-care is as old as illness if not as humans. Self-care is a lay behavioural response of individuals to promote or restore their health. One form of self-care is self-medication. Drugs are central to self-medication. Although there are arguments for and against self-medication, its contribution to promote health, and prevent and treat diseases is beyond doubt. Self-medication is the selection and use of medicines by individuals to treat self-recognized illnesses or symptoms of illnesses. Socio-demographic and socio-economic variables affect self-medication. In this study, an attempt has been made to assess self-medication practices with modern drugs and consumers drug knowledge in Addis Ababa. Methods: A multi-stage stratified sampling of drug retail outlets and drug consumers (actual drug users and messengers) was designed and used. Structured questionnaires to assess prospective self-medication practices and consumers drug knowledge were employed. The data was analyzed using Epi Info Software. Results and Discussion: The respondents represented all socio-demographic characteristics such as age and gender (the proportion of males was twice that of females); education levels and occupation; religion (the majority being Orthodox Christians) as well as pregnant and breast-feeding women. The most frequently reported illnesses that prompted drug consumers for self-medication were found to be gastrointestinal (GI) diseases, headache/fever and respiratory tract infections (RTIs). More than 30% of illnesses/symptoms of illnesses were of less than 24 hours duration and more than 40% between one and seven days. The most common reasons for self-diagnosis and self-medication were non-seriousness of the diseases and prior experience about the drugs. More than 50% of the drug consumers requested drugs x by specifically mentioning the names of the drugs and one-fifth of them by telling their illnesses/symptoms of illnesses. The most frequently requested category of drugs were analgesics/antipyretics (more than 30%), antimicrobials (more than 25%) and gastrointestinal drugs (more than 17%). Assessment of drug knowledge revealed that drug consumers know not only the names of OTC drugs but also other potent drugs, indicating widespread use of the latter. For example, among the top fifteen frequently recalled drugs five were antimicrobials. Drug consumers had also some dosage form preferences, the highest being injections and tablets for messengers and for actual drug users, respectively. Multivariate analysis showed that there is association between illness/symptoms of illness with the duration of illness and source of advice/information for self-medication (p value less than 0.05). Strong association (p value = 0.0000) was observed between the source of advice/information and the frequently requested category of drugs, some socio-demographic variables with sources of advice/information, knowledge of drugs, and the frequently requested category of drugs. Conclusion: Self-medication is widely practiced by all categories of respondents for a wide range of illnesses/symptoms of illnesses. More than 100 different types of drugs were used for self-medication. Although there is some apparent consumers drug knowledge, it is suggested that the public has to be educated on the type of illnesses to be self-diagnosed and the type of drugs to be self-medicated. It is only then that responsible self-medication prevails to promote health and prevent/ treat illnesses.