Thesis (Ph. D.)--University of Hong Kong, 1976. / Also available in print.

Thesis (M.S.)--University of Wisconsin--Madison, 1970. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Two possible variables of the McKenzie/Stoughton blanching assay, namely amount applied to the test site and occlusion time have been investigated. Subsequently, two topical steroid preparations, Synalar cream (0,025% fluocinolone acetonide) and Betnovate cream (0,1% betamethasone 17- valerate) were extemporaneously diluted with five and six placebo bases respectively. Taking cognizance of the two possible variables, these diluted preparations were assessed in vivo using a modified version of the McKenzie/Stoughton blanching assay for blanching activity over a 14 month period. It was found that the base E45, which is slightly alkali, had the greatest effect on both preparations. In the case of betamethasone 17-valerate this base caused the conversion to the less active isomer, betamethasone 21-valerate whereas at the end of the 14 month test period it was found that the Synalar/E45 dilution contained no fluocinolone acetonide. Quantitative analysis of all the diluted preparations by high performance liquid chromatography using a reverse-phase system was performed. The data obtained from the systematic studies of the effects of varying concentrations and occlusion times were presented at the Eleventh National Congress of the South African Pharmacological Society

Several aspects of the human skin blanching assay were evaluated in an attempt to suggest improvements in the methodology of this assay. Three trials were performed in the unoccluded application mode, using two proprietary creams containing 0,1% betamethasone (as the 17-valerate). Preliminary observations of the influence of ambient temperature and relative humidity on the blanching response did not allow definite conclusions to be drawn. Studies on the number of observers required for reliable results of comparative blanching indicated that at least two trained observers should be employed. Analyses of the results of individual volunteers demonstrated the expected biological variability, and suggest that subjects selected for trials should represent a range of blanching responses. No sex-related differences in blanching responses were found, and both arms exhibited similar sensitivity to corticosteroids. Retrospective analysis of 95 040 observations of blanching responses showed that in the unoccluded application mode blanching is lowest close to the wrist, and in the occluded mode blanching is lowest close to the elbow. Studies on the method of transportation of Betnovate preparations suggest that topical formulations should not be exposed to temperature extremes during transportation. It is proposed that patients should not transport topical formulations in the holds of ships or aircraft, and that exporters and manufacturers should make use of special transportation and storage conditions. In a study of ten topical formulations from three countries it was found that there was no trend of products from one country consistently exhibiting superior blanching to products from the other two countries, or products from one country consistently exhibiting the lowest degree of blanching, although considerable differences in blanching responses were found in some cases. Interpretation of the results of these studies demonstrated the importance of employing a combination of statistical analyses, blanching profiles and AUC values when drawing conclusions regarding comparative bioavailability. A study of the blanching profiles of Betnovate cream included in all 16 trials performed during this work indicated that this preparation behaved in a similar fashion during all trials, thereby giving credence to the results of the trials

One of the primary contributing factors to the escalating costs of health care is the high cost of innovator pharmaceutical products. As a consequence, health authorities in various countries and in particular in the developing world have identified generic prescribing and generic substitution as possible strategies to contain the escalating costs of health care provision. There is therefore a need for formulation scientists in developing countries to invest more time in the research and development of generic formulations. Clobetasol 17-propionate (CP) generic cream formulations containing 0.05% w/w of the drug were manufactured and characterized using in vitro testing. Formulation development studies were preceded by the development and validation of an RP-HPLC with UV detection for the quantitation and characterization of CP in innovator and generic cream formulations during formulation development and assessment studies. Furthermore the in vitro release ates of CP release from innovator and generic cream formulations were monitored using a validated in vitro release test method developed in these studies. The formulation of CP cream products was accomplished using a variety of commercially available mixed primary emulsifiers, such as Estol® 1474, Ritapro® 200, Emulcire® 61 WL and Gelot® 64. Successful formulations were selected based on their ability to remain physically stable immediately after manufacture and for 24 hours after storage at room temperature (22°C). Estol® 1474 was found to produce an unstable cream and was therefore not investigated further. The other three emulgents produced stable creams, but only the in vitro release profile of CP from a cream manufactured to contain Gelot® 64 was found to be statistically similar to that of the innovator formulation. Therefore the cream containing Gelot® 64 was selected as the most appropriate prototype generic cream formulation and was characterized in vitro in terms of CP content, viscosity, pH and in vitro release rate. Data generated from these studies were compared to those of the innovator product, Dermovate® cream, using statistical methods. The CP content, pH and in vitro release rate data of the CP formulation were similar to those of the innovator product, however the intrinsic viscosity of Dermovate® cream was almost three (3) times greater than the intrinsic viscosity of the test formulation developed using Gelot® 64. The CP cream formulation developed in these studies was stored for 4 weeks at 40 ± 2°C and 25 ± 5% RH in an incubator and the formulation was found to be stable. A formulation has been developed and assessed and found to be suitable for use as a topical semi-solid dosage form for CP.

Thesis (MSc (Biochemistry))--University of Stellenbosch, 2004. / This study describes: 1. Investigation of product inhibition regarding the metabolism of progesterone in ovine adrenal micosomes. 2. The employment of novel cell culture techniques to study the effect of CYP17 and CYP21 concentration on adrenal progesterone metabolism. 3. The formulation of a mathematical model describing the behaviour of the observed results in point 2.

published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

Young, middle-aged and old rat adrenal gland steroidogenesis was measured in isolated, superfused glands and in their subcellular fractions before and after adrenocorticotropic hormone treatment. In the latter experiment, five corticosteroids were extracted from six different subcellular fractions. Superfused glands initially produced relatively high glucocorticoid levels; thereafter, production decayed asymptotically. Steroidogenesis by young and middle-aged glands was maintained at least 1.5 to 2.5 hours before it decayed; old glands were 50% less active than younger ones and production decayed within one hour. High cholesterol and progesterone levels in certain old gland fractions were associated with correspondingly reduced 11-deoxycorticosterone and corticosterone. It is suggested that synthesis of these glucocorticoids from their accumulating precursors weakens with age.

by Pik-ying Ng. / Bibliography: leaves 106-117 / Thesis (M.Phil.)--Chinese University of Hong Kong, 1983

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences