Effect of functional excipients on the dissolution and membrane permeation of furosemide formulated into multiple-unit pellet system (MUPS) tablets.

The effect of functional excipients (i.e. chitosan, sodium lauryl sulphate, NaHCO3, and CaCO3) formulated in multiple-unit pellet system (MUPS) tablets has been investigated on the dissolution and permeability of furosemide, a BCS class IV compound. Spherical beads were produced and compressed into MUPS tablets. MUPS tablet formulations were evaluated for hardness, disintegration, mass variation, friability, and dissolution (pH 1.2, pH 4.6, and pH 7.4). Ex vivo permeability studies were conducted across excised pig tissues (pyloric antrum and duodenal region) on selected experimental MUPS tablet formulations. Histological analysis was conducted on the tissues after exposure to selected experimental MUPS tablet formulations. Dissolution results in the 0.1 M HCl (pH 1.2) showed the highest effect of the excipients on furosemide release. Dissolution parameters showed increased dissolution of furosemide for the MUPS tablet formulations containing functional excipients: a 4.5-10-fold increase in the AUC values, the %max showed a 60-70% increase and up to a 19-fold increase in DRi was seen. Permeability results revealed a 2.5-fold higher cumulative percentage transport for selected formulations. The results proved that functional excipients incorporated into beads, compressed into MUPS tablet formulations increased furosemide release as well as permeation across excised intestinal tissues.

Low molecular weight quaternised chitosan (11): in vitro assessment of absorption enhancing properties.

N-Trimethyl chitosan chloride (TMC; high molecular weight) and N-trimethyl chitosan oligosaccharide (TMO; low molecular weight) with different degrees of quaternisation were synthesised and evaluated for their absorption enhancing properties across mucosal epithelia. These quaternised chitosan derivatives (0.0625% w/v-0.5% w/v) showed a significant decrease in the transepithelial electrical resistance (TEER) of cultured rabbit tracheal epithelial cell monolayers as compared to the control. The degree of quaternisation and concentration of the compounds influenced the extent of the reduction in TEER. Higher degrees of quaternisation and an increase in the concentration of the compound were associated with a more pronounced reduction in the TEER. The TMO derivatives seemed to be more effective in lowering the TEER of tracheal cell monolayers as compared to the TMC polymers. Ciliary beat frequency (CBF) is the main defence mechanism of the respiratory tract and is therefore a useful parameter in evaluating the toxicity of nasally administered drugs and additives. The effect of the synthesised chitosan derivatives on the CBF of human nasal epithelial cells at pH 7.4 was determined by a method based on an analogue contrast enhancement technique. The TMO oligomers exhibited lower inhibition of the CBF of human nasal epithelial cells compared to that of the TMC polymers. It was proposed that this reduced effect on the CBF is due to the lower viscosity and molecular weight of TMO. However, no acute toxicity was found with any of the synthesised chitosan derivatives by means of the CBF tests conducted in this study.

Cardiovascular causes of death at Tshepong Hospital in 1 year, 1989-1990. A necropsy study.

Cardiovascular disease is the third most common cause of death in Tshepong Hospital in the western Transvaal, and the most common cause of death in patients older than 35 years. A prospective study was undertaken which included limited necropsies in 90 of the 167 cardiovascular disease deaths over 1 year. A reliable mortality pattern for cardiovascular deaths is described. Additionally, attention is paid to co-existing conditions. Conditions relating to cardiovascular disease, such as hypertension, benign hypertensive nephrosclerosis, atherosclerosis and obesity, were also evaluated. Cerebrovascular conditions were found in 32% of cardiovascular deaths. Intracerebral haemorrhage was found in 50% and cerebral infarction in 29% of cases. Fifty-seven per cent of cardiovascular deaths were due to cardiac conditions, the most common being pulmonary hypertension (31%), dilated cardiomyopathy and chronic rheumatic valvular disease (17% each) and hypertensive heart disease (14%). Forty-nine per cent of subjects were hypertensive, while 40% exhibited benign nephrosclerosis and only 3% of the examined vessels had signs of severe atherosclerosis. Tuberculosis was present in 13% of cases. The clinical diagnosis was the same as the final necropsy diagnosis in 38% of cases. These results emphasise the importance of performing necropsies to obtain reliable mortality statistics.

[The incidence of ischemic heart disease in white South Africans cremated in Pretoria, 1978-1985]. / Die insidensie van iskemiese hartsiekte onder blanke Suid-Afrikaners wat in Pretoria veras is, 1978-1985.

The prevalence of ischaemic heart disease was studied in a population selected on the basis of an application for cremation by the next of kin. In the age group 35-44 years 15.2% of the deaths were ascribed to ischaemic heart disease (IHD), while the corresponding figure in the general population was 27.2%. In females in the age group 45-54 years IHD was responsible for 9.3% of the deaths; the corresponding prevalence in the general population was 18.3%. The figures for all age groups and both sexes were 22% for the cremation group and 24.5% for the general population. In the economically active group (20-65) years, the figures were 20.0% for the cremation group and 30% for the general population. There was no significant difference in the IHD deaths between Afrikaans-speakers and other language groups. These findings are not necessarily applicable to the general population, as the cremation group is not truly representative, but the consistently lower prevalence of IHD suggests that there is over-reporting of this disease in unmonitored death certification.

Causes of death at Tshepong, a rural hospital, 1986-1987.

A prospective study was undertaken to determine causes of death at Tshepong Hospital in the western Transvaal over 1 year. Specific attention was paid to the accurate coding of causes of death; this entailed discussions with the attending doctor as well as 38 autopsies. Only 2.4% of deaths were coded under 'symptoms, signs and ill-defined conditions'. The 1046 deaths followed a typical Third-World pattern when classified according to the International Classification of Diseases (1979). Deaths during the perinatal period were additionally classified according to the recommendations of the Third Conference on Priorities in Perinatal Care in South Africa. The commonest cause of death was conditions originating in the perinatal period (19.2%), followed by infections and parasitic diseases (15.9%), diseases of the circulatory system (14.8%), endocrine, nutritional and metabolic diseases and immune-disorders (12.1%), and neoplasms (8.8%). The other main groups accounted for under 8% each. The commonest cause of death in all age groups above 35 years was diseases of the cardiovascular system, and the commonest cause of death among females aged 15 - 35 years was complications of pregnancy, childbirth and the puerperium. The hospital maternal mortality rate was 4.7/1,000 deliveries and the hospital perinatal mortality rate was 53/1,000 deliveries.