Thesis (Ph. D.)--Columbia University, 1937. / Vita. Bibliography: p. 47-49.

Thesis (Ph. D.)--Columbia University, 1929. / Includes vita. eContent provider-neutral record in process. Description based on print version record.

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Magister Scientiae Dentium - MSc(Dent) / Objectives:Substances leaching from denture- base polymers have been associated with cytotoxicity and allergic reactions. This study examined the effect of polishing,mixing ratios, water immersion temperatures and different thicknesses on the sorption and solubility of a heat-polymerized, denture-base polymer. The effect of different water immersion temperatures on the flexural strength of the denture base, was tested as well. The next component of this study, is the testing of the most significant sorption and solubility findings on in vitro cell viability. Materials and Methods:Disc shaped specimens from a heat-polymerized, denture-base polymer (Vertex®) were prepared, based on ISO 1567 specifications for sorption and solubility testing, following the manufacturers’ instructions. The following tests were performed: 1) Sorption and solubility of two groups (n = 12 each) of polished and unpolished discs were established and compared by means of the Mixed procedure; 2) Sorption and solubility of three groups (n = 12 each) with different mixing ratios were compared by means of the Mixed procedure; 3) Four groups (n = 14 each) were immersed in water at different temperatures, sorption and solubility were compared by means of pairwise comparison and the Median test; 4) Specimens with different thicknesses (n = 36) were compared, again, by means of pairwise comparison and the Median test; 5) To test the influence of different water-soaking temperatures on the flexural strength of the disc, strips were prepared from the disc used in test no. 3. The flexural strength was compared, by means of the Median test; 6) To test the influence of no postpolymerization treatment, polishing and water immersion on the cytotoxicity of mouse fibroblast cells, (n = 9) for each test group, were prepared. A preliminary test was performed beforehand, over a period of 24 hours, up to a maximum period of four weeks. The Balb/c 3T3 mouse fibroblast cells were cultured and incubated for 24 hours in Eagles medium. Eluates prepared from the disc and medium without any disc (control) replaced the medium. Cytotoxicity was assessed by MTT-assay. Optical density values were obtained at 24 and 48 hour intervals. The data was analyzed by means of the Means procedure.Results:In the entire thesis, the data was analyzed using SAS on a 0.01 probability level.Between polished and unpolished groups, no significant difference in water sorption (p> 0.01) was found, but there was a difference in solubility (p<0.01).Different mixing ratios did not alter sorption (p = 0.34) or solubility (p = 0.68).However, a difference (p<0.01) in sorption and solubility was found among the different temperature and thickness groups. Soaking the denture base in water at different temperatures did not alter its flexural strength (p = 0.48). Cell viability levels were noted in all the experimental groups in the MTT assay test. The analysis was a two-factor study, with one factor being the group, and the other, being time. The interaction between these factors was found to be significant, indicating that the effect of the groups varied by time (and vice versa).Conclusion:The processes of the soaking in warm water and the polishing of a denture-base polymer, reduce its solubility. Therefore, it is recommended that dentures are soaked in warm water before polishing. Within the limits of this study, the mixing ratios may be changed without affecting sorption or solubility. As solubility increases within the increasing denture-base thickness, it is recommended that unnecessarily thick dentures be avoided.Short- and long-term exposure to eluates of a PMMA, has a negative effect on cell viability. For water-stored and polished discs, this effect is time-dependent, with a higher viability for 48 hours’, than for 24 hours eluates. Polishing is associated with lower solubility. At 24 hours, the polished discs, indeed, had a lower cytotoxic effect than the untreated discs: it may be recommended that dentures be polished on the fitting surface as well.The cytotoxic potential of PMMA-eluates appears to fluctuate over time.

[From Introduction]. In 1955, Dry and Gledhill, both formerly of this Department, published their paper on the Solubility of Mercurous Chloride in Water at 25°0, and it was originally intended that this thesis should be an extension of the study to cover the temperature range from 5 t o 55°0. A preliminary investigation at 25°0, however, failed to yield results which were consistent with their findings, even though their apparatus and experimental technique were used. In an effort to resolve these difficulties their method of saturating the calomel in the conductance cell was thoroughly investigated, and as this procedure was found to be responsible, it was necessary to evolve an entirely new approach. The technique finally adopted was to saturate the mercurous chloride solutions by mechanical stirring in siliconed vessels and to carry out the conductance, pH, and total mercury concentration measurements on the filter ed solution. This method gave good results, and was free from the many extrapolations prevalent in the original procedure.

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Charles University, Faculty of Pharmacy in Hradci Králové Department of: Pharmaceutical Technology Supervisor: Assoc. Prof. PharmDr. Zdenka Šklubalová, Ph.D. Consultant: Mgr. Jana Brokešová Student: Andrea Suther Bunes Title of Thesis: Study of influence of hydrophilic carriers on the dissolution rate of a BCS II drug The aim of this thesis was to study the effect of mixing and co-milling with hydrophilic carriers on the dissolution rate of a model BCS II drug meloxicam. The mixtures of two different drug loads (1-1, 1-8) were characterized for granulometric and dissolution parameters. USP-4 apparatus assembled with a flow-through powder cell (an open loop) was used to estimate meloxicam relative dissolution rate rrel (min-1 ). Mixing with lactose, particularly in a higher ratio, increased the relative dissolution rate in comparison to the pure meloxicam. The effect was further increased by co-milling, but an unfavourable event of agglomeration occurred, especially for the 1-1 drug-excipient ratio sample. Adding chitosan solved this problem due to the formation of interactive mixture. The co-milled sample containing chitosan and lactose in a 1-8 ratio showed the highest rrel = 0.48 min-1 .

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The effect of triacetin in combination with common cosolvents on the solubility of phenytoin and diazepam was studied. The cosolvents were PEG 400 and propylene glycol. In addition, the data were used to test the following model: UNFORMATTED EQUATION FOLLOWS: log Sᵈ(c,p,w) = log Sᵈ(w) + f(c)σᵈ(c) + [Sᵖ(w)10(f(c)σᵖ(c))/D(p)] σᵈ(p). UNFORMATTED EQUATION ENDS. The term on the left side of the equation is the solubility of a drug in the ternary system. This is related to the aqueous solubility of the drug, the solubility of the drug in a completely miscible organic solvent (CMOS), and the solubility of the partially miscible organic solvent (PMOS). This model was proposed by Gupta et al. (1989) and predicts the solubility of a ternary system composed of a CMOS and PMOS. The results indicate the triacetin does increase the solubility of the two poorly water-soluble drugs. There is good correlation between the observed and predicted increase in the solubility of the drugs.

This thesis covers a range of methodologies to provide an account of the current (2010-2014) state of the art and to develop new methods for solubility prediction. We focus on predictions of intrinsic aqueous solubility, as this is a measure commonly used in many important industries including the pharmaceutical and agrochemical industries. These industries require fast and accurate methods, two objectives which are rarely complementary. We apply machine learning in chapters 4 and 5 suggesting methodologies to meet these objectives. In chapter 4 we look to combine machine learning, cheminformatics and chemical theory. Whilst in chapter 5 we look to predict related properties to solubility and apply them to a previously derived empirical equation. We also look at ab initio (from first principles) methods of solubility prediction. This is shown in chapter 3. In this chapter we present a proof of concept work that shows intrinsic aqueous solubility predictions, of sufficient accuracy to be used in industry, are now possible from theoretical chemistry using a small but diverse dataset. Chapter 6 provides a summary of our most recent research. We have begun to investigate predictions of sublimation thermodynamics. We apply quantum chemical, lattice minimisation and machine learning techniques in this chapter. In summary, this body of work concludes that currently, QSPR/QSAR methods remain the current state of the art for solubility prediction, although it is becoming possible for purely theoretical methods to achieve useful predictions of solubility. Theoretical chemistry can offer little useful additional input to informatics models for solubility predictions. However, theoretical chemistry will be crucial for enriching our understanding of the solvation process, and can have a beneficial impact when applied to informatics predictions of properties related to solubility.