Browsing by Author "Dangor, Cassim Mahomed."

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Antimicrobial and chemical analyses of selected bulbine species.
(2000) Mocktar, Chunderika.; Essack, Sabiha Yusuf.; Rogers, B. C.; Dangor, Cassim Mahomed.
The use of plant materials for the treatment of various diseases is very common in African countries. As traditional medicine used by the rural people does not always have a proper scientific basis, research programmes have to be undertaken to evaluate their therapeutic efficacy and safety. In traditional African medicine various Bulbine species are used to treat a number of conditions including sexually transmitted diseases, wound infections, dysentery and urinary tract infections. The Bulbine species belong to the family Asphodelaceae. There are over fifty South African Bulbine species and they are mostly herbs. Their leaves are evergreen and succulent in appearance. Bulbine species have thick fleshy tuberous roots, are easy to grow, are able to withstand drought and heat and are able to grow in poor soil. There is very little documented information on the antimicrobial activity and chemical properties of the Bulbine species. Therefore research programmes of this nature have to be undertaken. Various Bulbine species, viz., B. natalensis Bak, B. frutescens Willd (yellow flowers), B. narcissifalia Salm Dyck, B. abyssinica A Rich and B. frutescens Willd (orange flowers) were collected. The plants were washed with tap water, air dried and separated into the different components. Each component was cut into small pieces and immersed in methanol: dichloromethane (1:1, v/v) for extraction. The organic solvent was decanted from the plant material and evaporated under reduced pressure. The resultant crude extracts were stored in glass vials in the freezer. In addition, the roots, stems and leaves of B. natalensis and B. frutescens (yellow flowers) were extracted aqueously. The crude organic and aqueous were subjected to various tests to evaluate their antimicrobial and cytotoxic potential. To evaluate their antibacterial activities, the Disk Diffusion and Bore Well Methods were employed. The crude extracts were tested against various pathogens implicated in wound and urinary tract infections and dysentery. In these experiments the Disk Diffusion Method produced better results than the Bore Well Method. The crude organic and aqueous extracts were found to be effective against many of the bacteria used in this study including K. pneumoniae, S. aureus, S. typhi and S. flexneri which are considered to be troublesome pathogens. The TLC bioassay was employed to evaluate the antifungal potential of the various crude extracts against Aspergillus and Penicillium and the Disk Diffusion and Bore Well methods were used to evaluate the antifungal potential of C. albicans. The Bulbine species displayed no antifungal activity against Penicillium and limited antifungal activity against Aspergillus. The two method used to evaluate the antifungal activity of. C albicans was chosen because C. albicans grows in a similar manner to bacteria on solid and liquid culture media. Only the root extracts of the two B. frutescens varieties were inhibitory to C. albicans. The Brine Shrimp Bioassay was used to ascertain the cytotoxic potential of the crude extracts. The majority of the extracts were cytotoxic at the most concentrated dilution (i.e., dilution 1) but not cytotoxic at the lower dilutions. The only extracts that were not cytotoxic at the most concentrated dilution were the organic extract of the root of B. frutescens (yellow flowers), the organic extract of the root of B. narcissifolia and the organic extract of the leaf of B. abyssinica. TLC and column chromatography was carried out to evaluate the chemical composition of the Bulbine species. The TLC indicate that this technique could be a valuable tool in identifying the different species in the genus Bulbine. Column chromatogram was carried out on the extract which displayed a significant amount of antibacterial activity against the bacteria used in this study. The stem extract of B. natalensis was chosen for further analysis. The stem extract was fractitioned into different fractions but unfortunately none of the chemical component could be identified. According to the results obtained in this study, there is considerable scope for further studies of this genus.
Bioavailability studies on various dosage forms of the anorectic, diethylpropion hydrochloride.
(1984) Dangor, Cassim Mahomed.; Veltman, A. M.
The stereo-chemistry, structure activity relationships and the metabolism of the anorectic drug, diethylpropion hydrochloride, have been reviewed briefly, together with the analytical methods for the determination of this drug and its metabolites in biological fluids. In addition, the physico-chemical properties, mode of action, pharmacology and uses of the metabolites have been presented. A comprehensive review on general principles of salivary excretion of drugs and their therapeutic drug monitoring in saliva with relevant published data on saliva/plasma drug concentration relationships has been outlined. Sensitive and specific assay procedures, based on gas-liquid chromatography for the identification, separation and determination of diethylpropion and its two major metabolites i.e. ethylaminopropiophenone (11) and diethylnorpseudoephedrine (IV) in aqueous and biological fluids, have been developed. These methods were used to study the urinary excreUon as well as saliva and plasma levels of the two major metabolites and, where possible, the unchanged drug, in man. Sustained release pellets with diffusion rate-controlled membranes were employed to control the rate of input into the body by oral or rectal route of administration. Urinary excretion data and plasma levels of metabolites 11 and IV in volunteers, where the urine was controlled at an acidic pH, were used for the evaluation of the bioavailabilities of different dosage forms of diethylpropion hydrochloride. The concentrations of metabolites 11 and IV were also measured in saliva and in plasma after administration of the drug in different doses and dosage forms: relationships between saliva and plasma concentrations (S/P) and between urinary excretion rates and plasma concentrations (U/P) were developed for each of the two metabolites during plateau levels after oral administration of the sustained release pellets (Lot R 7773). The potential use of salivary excretion of the metabolites as an index to monitor their plasma levels and bioavailabilities, was examined. The distinct advantage of using a subdivided controlled release system (i. .e. sustained release pellets) to a single unit sustained release tablet (erosion-core type) in relation to influence of the physical presence of food on the rate and extent of absorption has been demons t rated . It was found that the route of administration (oral or rectal) did not significantly affect the bioavailability of the sustained release pellets. The study also involved the investigation of the release of the drug from the pellets. Because the release control step was diffusion, no significant influences on dissolution rates were observed with the use of different dissolution test models and agitation intensities. The influence of the concentration and composition (presence of cations viz. Na+ and K+ i~r anions viz . phosphate and borate) of the dissolution medium on the release of the drug from sustained release pellets, was also studied. Any potential changes in the dissolution pattern on storage of the pellets under different conditions (4°C, room temperature and 37°C) ovrr, a period of at least one year, were investigated. The in vitro and in vivo correlations of two lots of sustained release pellets, each exhibiting different dissolution profiles, and administered rectally and orally, were developed: the in vitro data on the free drug were related to the sum of the urinary excretion data of metabolites II and IV. An attempt to use an empirical approach to predict urinary excretion rate profiles of metabolite II after oral administration of the sustained release pellets, was promising; the calculated profiles were reasonably comparable with those of in vivo studies. However, the complete validity of such equations needs further investigations.
Drug-related problems among geriatric outpatients at a public sector hospital : an intervention study.
(2000) Moodley, Pathma.; Dangor, Cassim Mahomed.; Perumal, D.
Introduction: Although drug-related problems (DRPs) are known to be prevalent in elderly patients, there are not many studies that have been performed in geriatric outpatients at public health facilities in South Africa. Thus, the prevalence of DRPs in elderly outpatients attending Addington Hospital was investigated and suitable preventive intervention strategies to overcome or minimise these DRPs were developed. Research Methodology: The study was conducted in two phases. Phase 1 was conducted in March and April 1998, during which 281 elderly patients on chronic medical treatment were chosen for the study by systematic random sampling, according to specific inclusion criteria. Data collection was via a retrospective review of the elderly patient's medical notes and by personally interviewing the patient. Two research instruments were used in this phase. The customised Patient Profile (PF) form helped to delineate DRPs in the elderly patients. A Prescription Intervention Form (PIF) was used to inform the prescriber of the DRP and to make recommendations to change the drug therapy in order to overcome the DRP. In phase 2 of the study, intervention strategies were devised to address some of the major DRPs identified in phase 1 of the study. A patient counselling leaflet, prescribing guidelines for geriatric patients and a protocol for counselling of in-patients were developed. In addition, two DRP reporting systems were developed for surveillance of adverse drug reactions and medication errors during dispensing. Results and Discussions: Most geriatric subjects suffered from multiple, chronic conditions, these being hypertension (64.8%) followed by ischaemic heart disease (43.8%), musculoskeletal disorders (arthritis or gout) (42.7%), diabetes (29.2%), chronic obstructive airways disease (13.2%), hypercholesteremia (11.7%) and arrythmias (atrial fibrillation) (11.0%). The 281 patients were taking 1730 prescribed drugs, with a mean of 6.2 (range 3 to 15) prescribed drugs per patient. An astounding 45.6% of the total geriatric patients were taking or using between 7 to 9 medicines and 10.3% were taking or using between 10 to 15 medicines. The antihypertensives (15.9%) were the most widely prescribed drugs followed by medicines acting on CNS (10.9%), coronary vasodilators (9.1%), diuretics (9.1%) and medicines acting on the musculoskeletal system (8.7%). A total of 856 actual DRPs experienced by 262 geriatric patients (93.2%) ranged from 1 to 11 DRPs. The greater the number of prescribed drugs the greater the actual DRPs experienced by geriatric patients (p = 0.000). The most common DRPs were those involved in drug safety (56.6%); effectiveness of the drug therapy (20.8%); compliance (7.8%) and indication of drug therapy (7.6%). 159 elderly patients (56.6%) experienced 223 adverse effects either with their current or past prescribed medicines. The most common ADRs were as follows: gastro-intestinal ulceration (11.0%), cough (9.3%), diuretic side effects (dehydration, fatigue, hypotension, etc) (7.1%), constipation (6.8%), equilibrium problems (6.4%) and headaches (6.4%). For those DRPs warranting interventions, the mean number of prescription interventions in the entire sample population of 281 elderly patients was 0.65 ± 1.16. 87 elderly patients (30.1 %) had from 1 to 4 interventions on their current prescription. The most common prescription interventions were on problems involving drug therapy monitoring (26.9%), safety of drug therapy (26.5%), indication of drug therapy (17.5%), prescribing errors (15.3%) and prescription information omission (11.1 %). The three intervention strategies and DRPs surveillance reporting systems were successfully devised and developed. Conclusions: A profile related to the elderly patient's medical history and pharmacotherapy was completed for each of the 281 patients. General trends of prescribing pattern prevalence of DRPs and the prescribed inappropriate medication was established. The interventions of problem prescriptions were based on a newly developed PIF. The development and implementation of suitable intervention strategies to minimise DRPs were as follows: a compliance information leaflet, prescribing guidelines and the protocol for counselling in-patients. A medication error form as well as an adverse drug reaction reporting forms was developed for surveillance of DRPs. The recommendations for clinical practice and directions for future research that are presented should help to make drug therapy in the elderly safer and more effective.
Formulation and evaluation of modified release eudragit® matrices containing diclofenac sodium.
(1998) Hurbans, Nivriti.; Dangor, Cassim Mahomed.; Chetty, D. J.
The aim of the present study was to formulate oral modified release matrices of diclofenac sodium, using the Eudragit® polymers. In addition to the formulation processes, numerous variables had to be investigated, which included dissolution variables, formulation variables, and processing variables. The application of the tabletting technique as well as the use of Eudragit® polymers to modify the release of diclofenac sodium is motivated at the outset. A comprehensive review of modified drug release, the use of the tabletting methodologies and the application of Eudragit® polymers are presented. In-process quality control tests as well as the mechanisms and interpretation of the dissolution process are outlined. Diclofenac sodium, a potent nonsteroidal anti-inflammatory drug, was used in the present study, hence a brief review of this drug is also presented. The direct compression as well as the wet granulation tabletting methods were investigated. The major limitation of the direct compression method was found to be the lack of suitable flow properties of the powder blend. The wet granulation technique however, was successfully employed to prepare various diclofenac sodium Eudragit® matrix tablets. All tablets were prepared to contain 100 mg diclofenac sodium. The optimisation process was shown to be an integral procedure in influencing the matrix characteristics. In addition, it was shown that drug release was significantly influenced by different types and concentrations of Eudragit® polymers. A specific formulation was selected to investigate the integrity of the matrices produced by the wet granulation technique. The drug release profile of a commercially available modified release preparation containing diclofenac sodium viz. Veltex® 100 CR (reference standard) was also obtained. A comparison of the drug release profiles of Veltex® 100 CR capsules and the selected formulation showed them to be markedly dissimilar. Hence, a strong motivation is provided for rationalising the selection of the particular formulation in the present study, that was shown to release diclofenac sodium optimally. The selected formulation was prepared using a combination of the Eudragit® RL and Eudragit® RS polymers. In vitro dissolution studies on the selected as well as various other formulations demonstrated the wet granulation method to be both predictable and reproducible. However, absolute drug release independency of dissolution methods, media and agitation rates was unattainable. Furthermore, drug release was shown to be pH dependent. The selected formula was subjected to certain formulation and processing variables. An increase in the concentrations of lactose and starch was shown to increase drug release. Different types of diluents were also shown to influence drug release from the tablets. The method of incorporation of the lubricant, magnesium stearate, was investigated. Compression studies demonstrated the susceptibility of the tablets to changes in drug release behaviour and morphological characteristics as the hardness was varied. X-ray diffraction studies demonstrated that the processes of granulation and compression did not promote any atomic rearrangement of the drug and Eudragit® polymers. Scanning electron microscopy was useful in investigating the integrity and surface morphology of newly formulated as well as stored samples, while energy dispersive x-ray microprobe analysis adequately revealed the elemental composition of the tablets. The selected formulation was shown to be stable at room temperature (21 ±1°C) and low temperature (5± 1°C), while storage at 37°C with 80% relative humidity and 40°C demonstrated significantly decreased drug release behaviour during short term (3 months) stability testing. Tablet hardness evaluated during the stability testing showed that there were virtually no differences in tablet hardness between the room temperature and low temperature samples, while tablets stored at 37°C with 80% relative humidity and 40°C hardened considerably. However, tablet potencies and the moisture content of the samples were not significantly influenced during the storage period. In addition to usual observations and mathematical manipulation, some of the data generated from this study were also evaluated statistically.
Formulation, evaluation and characterization of an oral modified realease naproxen sodium preparation.
(1997) Moopanar, Kevindren Ramachandran.; Dangor, Cassim Mahomed.
The motivation for the present study is systematically presented and the aims and objectives of the study are clearly defined. A comprehensive review on modified release drug delivery has been presented to provide the basis for the meltable aqueous dispersion technique as an approach to the formulation of a multiple-unit oral modified release drug delivery system. In addition, a brief discussion on the theory of dissolution testing and the mechanisms and interpretation of the dissolution process has been presented. Naproxen sodium, a potent non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic activity employed in the study, has been briefly discussed. In the present study, the coacervation phase separation technique utilizing ethylcellulose was initially investigated but proved unsuccessful in producing a formulation displaying suitable drug release characteristics. Subsequently, the meltable aqueous dispersion technique utilizing cetostearyl alcohol was successfully employed to formulate a multipleunit modified release naproxen sodium preparation containing 550 mg of naproxen sodium. The use of cetosteary!alcohol, as·a·retarding material, generated modified ·drug release characteristics as a function of its content. Magnesium stearate (anti-tackiness agent) and Span 20 and Tween 60· (surfactants) were incorporated in the formulation to optimize particle size and sphericity. The influence. of various formulation variables on drug release characteristics were investigated: An optimized formulation displaying a desirable modified release profile of naproxen sodium was achieved employing a 1:1 ratio of naproxen sodium:cetostearyl alcohol, 2% m/m .. .. magnesium stearate, and 1%m/m Span 20 dispersed in a liquid manufacturing vehicle of pH 0.6 containing 2% m/m Tween 60. In vitro dissolution studies on the selected formulation showed drug release to be predictable and reproducible, dependent on the dissolution method, agitation rate, and the pH of the dissolution media (i.e. pH-dependent drug release). The density of the microspheres was shown to decrease as the concentration of cetostearyl alcohol increased whilst the mean specific surface area increased with increasing concentrations of cetostearyl alcohol. Differential scanning calorimetric studies reveals a change in the thermograms which is suggestive of eutectic formation. Scanning electron microscopy proved useful in evaluating the integrity and surface morphology of the microspheres as well as in elucidating the drug release characteristics of the formulation. Energy dispersive x-ray microprobe analysis revealed the elemental composition of the microspheres to be a composite of the pure ingredients. X-ray mapping and the line scan depicted the homogenous distribution of drug within the microspheres and confirmed that the formulation is a matrix-type modified release I' preparation. Stability studies were performed on the selected formulation at room temperature (21 :t 1°C), 40°C, 37°C with 80% relative humidity, and at low temperature (5 :t 1°C). The shelf-life of the selected formulation was determined to be 1.29 years. Applying the data to five different kinetic models to investigate the drug release mechanisms showed that first order and cube-root release characteristics were exhibited by the microspheres.
An investigation of the antidiabetic herbal remedies used by traditional healers in Northern KwaZulu-Natal and their effect on blood glucose levels.
(1998) Ziqubu-Page, Thembelihle Thandekile.; Chetty, Manoranjenni.; Makubalo, L. E.; Dangor, Cassim Mahomed.
This research study undertook to investigate and evaluate for efficacy and safety, the herbal remedies used for treating Diabetes mellitus in northern KwaZulu-Natal. In addition, it sought to gain knowledge and better understanding of traditional healing systems and the medicinal use of the natural flora. During the process of assimilating the desired information, the epidemiological and socio-economic factors which determine the form of medicine chosen by rural people in the region, were quantified. Both aspects of explanatory studies i.e. experimental and observational were used. Firstly, to evaluate the safety of the two herbal remedies, laboratory animals were given an oral dose of the herbal medicine and observed for a period of 14 days. Efficacy was assessed by treating Streptozotocin-induced diabetic rats with the herbal remedies and comparing their effect on blood glucose with that of a conventional sulphonylurea. The second part of the study was observational and it involved monitoring human subjects (patients) for twelve months, who were already taking the herbal preparations (n=56) and comparing their prognoses with that of a group taking conventional medicine (n=97). A third group using both types of medicine (n=42) was included as control measure for a possible confounding factor. Main outcome measures; Both subjective and objective measures of the perceived health of the diabetic patients were measured, as well as the determinants of using traditional medicine versus conventional medicine. The battery of toxicity tests which utilises behavioural and functional observations of the laboratory animals, yielded no signs of toxicity or abnormal behaviour. The histopathological examination results of the sample organs from the treated rats also revealed no signs of abnormality that could be attributed to the herbal remedies tested. There was no sex variation recorded in the response. The first HP tested (HP-1) demonstrated minimal hypoglycaemic effect whereas HP-2 significantly lowered the blood glucose of the streptozotocin-induced diabetic rats by an average of 59%. This was comparable to the conventional medicine (Glibenclamide) used in the experiment. After 12 months of follow-up, 93 % of traditional medicine users (n=56) were convinced that their blood sugar was controlled because of the traditional remedy they were using. The proportion of diabetic cases who used conventional medicine were no better off than those who used traditional medicine or vice versa. Health status and the financial situation (income) of the respondents greatly influenced their choice for diabetic treatment. The herbal remedies that were investigated were non-toxic and safe for use and internal consumption. One preparation demonstrated a significant hypoglycaemic effect, which was comparable to the conventional allopathic medicine used in treating Diabetes mellitus. This study should serve as a springboard to encourage more pharmacological evaluation of herbal medicines.
Pharmaceutical availability on newly formulated oral sustained release pellets containing the antihistamine, chlorpheniramine maleate.
(1991) Mathir, Zohra Mohamed.; Dangor, Cassim Mahomed.; Veltman, A. M.
The main objective of the present study was to determine the feasibility of obtaining aqueous polymer-coated pellet formulations using EudragitR NE 30 D dispersion and chlorpheniramine maleate as the model drug. Many factors influence the rate of drug release from coated beads including, the substrate, the coating formulation and the coating process. A drug release profile that was comparable to that of the reference standard, DykatussR Capsules was obtained with a formulation employing 8.3% EudragitR NE 30 D, 0.5% talc and 1% polyethylene glycol. In vitro dissolution tests on this formulation showed drug release to be predictable, reproducible and independent of the dissolution methods or media. Short term storage confirmed the stability at room temperature (20°C) and low temperature (5C). Scanning electron micrographs of pellets stored at elevated temperatures i.e. 37°C with 80% relative humidity and 40°C illustrated the phenomenon of 'further gradual coalescence' which corresponded to the decrease in release of drug from the pellets.