Dale Eric Wurster

BASELINE STUDIES OF THE CLAY MINERALS SOCIETY SOURCE CLAYS: SPECIFIC SURFACE AREA BY THE BRUNAUER EMMETT TELLER (BET) METHOD

Specific surface area measurements of The Clay Minerals Society source clays were made by the Brunauer, Emmett and Teller (BET) method of adsorption of nitrogen gas. Two replicate measurements of specific surface area were performed for each source clay. All pair values were within 3%, which is very good agreement for this type of measurement.

Effect of Process Variables on the Microencapsulation of Vitamin A Palmitate by Gelatin-Acacia Coacervation

Microcapsules of vitamin A palmitate were prepared by gelatin-acacia complex coacervation. The effects of colloid mixing ratio, core-to-wall ratio, hardening agent, concentration of core solution, and drying method on the coacervation process and the properties of the microcapsules were investigated. The microcapsules of vitamin A palmitate were prepared using different weight ratios of gelatin and acacia, that is, 2:3, 1:1, and 3:2 under controlled conditions. The other factors studied were 1:1, 1:2, and 1:3 core-to-wall ratios; 30, 60, and 120 min of hardening time; 2, 5, and 10 ml of formaldehyde per 280 g of coacervation system as a hardening agent; and 30%, 40%, and 50% w/w vitamin A palmitate in corn oil as a core material. The drying methods used were air drying, hot air at 40°C, and freeze-drying. The results showed that spherical microcapsules were obtained for all conditions except for 30 min of hardening time, which did not result in microcapsules. The optimum conditions for free-flowing microcapsules with a high percentage of entrapped drug were 1:1 gelatin-to-acacia ratio and 1:2 core-to-wall ratio when hardening with 2 ml formaldehyde for 60 min and using 40% w/w vitamin A palmitate in corn oil as the core concentration. In addition, drying the microcapsules by freeze-drying provided microcapsules with excellent appearance.

Surface Characterization of Activated Charcoal by X-Ray Photoelectron Spectroscopy (XPS): Correlation with Phenobarbital Adsorption Data

X-ray photoelectron spectroscopy (XPS) was used to identify the functional states of carbon existing on the surfaces of various activated charcoals. The relative percentages of carbon, oxygen, and detectable trace elements comprising the activated charcoal surfaces were determined. Analysis of the carbon core-electron binding energy region revealed the existence of one hydrocarbon state (C–H, C–C are indistinguishable) and three oxygen-containing functional states. These states were hydroxyls or ethers (C–O), carbon-yls (C = O), and carboxylic acids or esters (O–C = O). The C–O functional state contributed approximately 60–70% to the total percentage of oxygen-containing states. A very good correlation existed between the apparent areas occupied on the adsorbent surface per phenobarbital molecule and the relative percentages of the C–O functional state. Previously reported heat of displacement results for phenobarbital adsorption are now explained since the C–O state appears to be the primary site involved in the binding of phenobarbital by the activated charcoals.

X-Ray powder diffraction determination of the relative amount of crystalline acetaminophen in solid dispersions with polyvinylpyrrolidone

A powder X-ray diffraction technique has been developed to quantify the relative amounts of crystalline acetaminophen in powder mixtures with polyvinylpyrrolidone prepared by blending and recrystallisation. Four methods were used to prepare solid dispersions of acetaminophen and PVP: (a) mechanical mixing in a tumbling mixer or planetary ball mill, (b) co-precipitation, (c) freeze-drying and (d) recrystallisation. Changes in X-ray powder diffraction properties and the differences in solubilities showed that the amount of crystalline acetaminophen only decreased in mixtures where both acetaminophen and polyvinylpyrrolidone were soluble (ethanol) or partially soluble (water). The decrease in the amount of crystalline material was the result of the formation of a glass-like, amorphous solid solution. The formation of this amorphous material could be followed by X-ray diffraction analysis of powdered samples.

The determination of diffusion coefficients in semisolids by Fourier transform infrared (FT-IR) spectroscopy

A Fourier transform infrared (FT-IR) spectrometer with a horizontal attenuated total reflectance (ATR) cell was used to determine the diffusion coefficients of several liquids in two semisolid materials. The experimental setup was that of a system with one open and one closed boundary wherein the open boundary was maintained at constant concentration. While the liquid of interest was diffusing through the film of ointment, the concentration of liquid at the film surface in contact with the ATR crystal was determined at various times by means of IR absorption measurements. The depth of penetration of the IR radiation into the sample was approximately 0.6–0.9 µm at the wavelengths of analysis. Since the ointment thickness was 157 µm, it was reasonable to assume that only the penetrant reaching the lower boundary was being measured. The values of the diffusion coefficients were then calculated using an equation that appropriately modeled the aforementioned conditions. The liquids tested exhibited diffusion coefficients in anhydrous lanolin and in polyethylene glycol ointment that ranged from 0.56 to 7.2 × 10−7 and 0.68 to 5.7 × 10−7 cm2/sec, respectively. The expected molecular weight dependency was observed.

Preformulation Studies on the S-Isomer of Oxybutynin Hydrochloride, an Improved Chemical Entity (ICE™)

(S)-Oxybutynin HCl (S-OXY) is a white crystalline solid powder with an acicular particle morphology. Differential scanning calorimetry (DSC) thermograms revealed one characteristic endotherm at 116.2°C. On rescanning a sample heated to 120°C, no thermal events were distinguished in the temperature range 25°C to 150°C. Weight loss curves determined by thermogravimetric analysis showed a continuous, gradual weight loss of about 0.15% over the temperature range 30°C to 110°C, followed by a change in slope and more rapid weight loss beginning at 150°C. Observation by hot-stage microscopy confirmed the melting endotherm observed by DSC. Equilibrium moisture uptake studies indicated low water vapor uptake at low relative humidities (< 52.8%). At relative humidities of 75.3% and 84.3%, S-OXY first deliquesced and then converted to a lower melting point crystal form. X-ray powder diffraction (XRPD) data supported the DSC findings. S-OXY underwent degradation by ester hydrolysis at alkaline pHs. The kinetics of this reaction were studied at 25°C in carbonate-bicarbonate buffers. Observed rate constants of 0.008 h−1 and 0.0552 h−1 were determined at pH 9.69 and 10.25, respectively. The pKa of S-OXY was 7.75. The aqueous solubility of S-OXY was described as a function of pH and the free-base solubility. The mean partition coefficient log P was 3.33 using 1-octanol. The surface tensions of aqueous solutions of S-OXY decreased with increasing concentration, but no concentration-independent region was observed, indicating that S-OXY does not form micelles in aqueous solution. The dissolution rate of S-OXY from a compressed disk in 0.1 N HCl was rapid, whereas it was considerably slower at pH 7.4. Addition of 1% hexadecyltrimethylammonium bromide (CTAB) at pH 7.4 significantly improved the dissolution rate. S-OXY displayed very poor flow properties when compared to standard pharmaceutical excipients. XRPD results indicated that S-OXY exhibited a loss in crystallinity following ball milling. Hiestand tableting indices indicated that S-OXY has good bonding properties and forms strong compacts, but is likely to be susceptible to capping on ejection from the die. This indicated the need for a plastically deformable excipient such as Avicel PH-101 in tablet formulations.

The Role of Tear Proteins in Tear Film Stability in the Dry Eye Patient and in the Rabbit

Sigma receptors have been identified in the lacrimal glands of rabbits; stimulation of these receptors results in the modulation of protein secretion from acinar cells. 1–4 When acinar cells were incubated with various sigma ligands, it was established that increases and decreases in protein release could be used to identify agonists and antagonists.4 Following the application of a newly designed agonist, N,N-dimethyl-2-phenylethylamine HC1 (AF2975), to the rabbit eye, a statistically significant increase in total protein was observed, when compared to either baseline values or the fellow eye.3 Tears were collected, and protein fractions were separated into various fractions with the use of size-exclusion high-pressure liquid chromatography (SE-HPLC).4 In particular, a 23 min protein fraction (about 16–18 kDa) was found to increase by 150% and 90% at 10 and 60 min, respectively following the topical application of AF2975 (50 μl of 0.15%) to the rabbit eye. Other protein peaks also showed an increase, but much less than the 23 min peak. Following desalting and concentrating, it was possible to separate the 23 min protein peak from rabbit tears into five isoforms using isoelectric chromatofocusing and a protein standard with a pI of 4.6. The isoforms were acidic with pIs higher than 4.6; however, the 23 min protein peak has not been specifically identified, which would require determination of its amino acid sequence. The function of the small-molecular-weight 23 min protein fraction is not known, but has been contrasted to the human tear fraction commonly referred to as tear-specific prealbumin (TSP) or as proteins migrating faster than albumin (PMFA).5–7

The effect of polymorphism on powder compaction and dissolution properties of chemically equivalent oxytetracycline hydrochloride powders.

In South Africa, oxytetracycline is identified as an essential drug; many generic products are on the market, and many more are being developed. In this study, six oxytetracycline hydrochloride powders were obtained randomly from manufacturers, and suppliers were compared. It was found that compliance to a pharmacopoeial monograph was insufficient to ensure the optimum dissolution performance of a simple tablet formulation. Comparative physicochemical raw material analysis showed no major differences with regard to differential scanning calorimetry (DSC), infrared (IR) spectroscopy, powder dissolution, and particle size. However, the samples could be divided into two distinct types with respect to X-ray powder diffraction (XRD) and thus polymorphism. The two polymorphic forms had different dissolution properties in water or 0.1 N hydrochloride acid. This difference became substantial when the dissolution from tablets was compared. The powders containing form A were less soluble than that containing form B.

Effect of charcoal and sorbitol-charcoal suspension on the elimination of intravenous phenobarbital

The effects of two different oral charcoal suspensions on the elimination of a 200 mg/70 kg, 1 h intravenous (i.v.) infusion of phenobarbital and the tolerances of the two regimens were determined in a randomized crossover study in six healthy male volunteers. Phenobarbital was given i.v. alone or together with 105 g of oral activated charcoal suspension or with 105 g of a commercially available sorbitol-charcoal suspension over a 36-h period. A 13–34% decrease in the area under the serum concentration time curve (AUC) for 0–60 h occurred with the administration of the activated charcoal, and a 19–52% decrease occurred with the commercial sorbitol-charcoal regimen. The mean apparent systemic clearance of total phenobarbital increased from 0.089 ± 0.019 ml/min/kg to 0.141 ± 0.029 and 0.146 ± 0.036 ml/min/kg with the charcoal and sorbitol-charcoal treatments, respectively. No significant change in the fraction of phenobarbital bound to protein was detected. The charcoal regimen caused constipation in one subject. All subjects taking the sorbitol-charcoal preparation experienced diarrhea: there were no changes in electrolytes with either charcoal suspension. All subjects preferred the sorbitol-charcoal preparation.

Aerosol OT Microemulsions as Carriers for Transdermal Delivery of Hydrophobic and Hydrophilic Local Anesthetics

The skin permeation enhancement of many kinds of drugs and cosmetic substances by microemulsions has been widely known; however, the correlations between microemulsion microstructures and the efficiency of skin permeation are not fully elucidated. Therefore, the aim of our study was to investigate the influence of microemulsion types on in vitro skin permeation of model hydrophobic drugs and their hydrophilic salts. The microemulsion systems were composed of isopropyl palmitate (IPP), water, a 2:1 w/w mixture of Aerosol OT (AOT) and 1-butanol, and a model drug. The concentrations of surfactant mixture and model drug were maintained at 45% and 1% w/w, respectively. The concentrations of IPP and water were 15% and 39% w/w, respectively, for oil-in-water (o/w) type and vice versa for water-in-oil (w/o) type. The samples were prepared by simple mixing and characterized by visual appearance, pH, refractive index, electrical conductivity, viscosity, and determination of the state of water and IPP in the formulations using differential scanning calorimetry. Transdermal flux of lidocaine, tetracaine, dibucaine, and their respective hydrochloride salts from the drug-loaded AOT-based microemulsions through heat-separated human epidermis was investigated in vitro using modified Franz diffusion cells. The o/w microemulsions resulted in the highest fluxes of the model drugs in base form as compared with the other formulations within the same group of drugs. Moreover, the skin permeation of drug from microemulsions depended on drug molecular structure and interaction between drug and surfactant.