Thesis (M.S.)--University of Wisconsin--Madison, 1961. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 35-36).

Thesis (M.S.)--University of Wisconsin--Madison, 1957. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 46-47).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1983. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 215-225).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1966. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliography.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1956. / Typescript. Includes abstract and vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1956. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 113-116).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1956. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 134-137).

From Introduction Chlorbutol , which is tri-chlor-tertiary-butanol, was first prepared by Willgerodt in 1886 (1). The reaction he used for its preparation is still used today, though slightly modified (2)(3)(4), and is suggested by its original name "acetone-chloroform". The substance was prepared by adding solid potassium hydroxide to a cold mixture of acetone and chloroform (5 ). Chlorbutol is a derivative of the trichlorinated derivative of methane, and its formation may best be described by the use of structural formulae.

Solubility of drugs in non-aqueous systems is very important in understanding the partitioning and transport behavior. The present study was undertaken to evaluate the entropic and enthalpic contribution to activity coefficient of organic compounds (polycyclic aromatic hydrocarbons, aliphatic acids, aliphatic alcohols etc.) in non-aqueous solvents. The activity coefficient can be written as: ln γ₁ = ln γ₁ᶜ + ln γ₁ʳ where superscript "c" and "r" denote entropic (combinatorial) and enthalpic contribution respectively. We selected three solvent systems: benzene, triolein and octanol. The different models considered in this study were Flory-Huggins, Scatchard-Hildebrand, UNIQUAC combinatorial and UNIFAC residual. A combination of Flory-Huggins and Scatchard-Hildebrand which accounts for both the entropic and enthalpic effects gives the best predictions in all the solvents considered.

Purpose: To develop an approach to formulating an injectable solution containing both hydrophilic and lipophilic drugs for subcutaneous administration. Based on the literature survey, isotropic medium chain mono-and diglyceride (MCMDG) systems were chosen for study. For this purpose, analytical methods were developed and validated. In vitro assessments of the MCMDG systems, and in vitro release and in vivo studies were conducted. Methods: The phase diagrams of the isotropic MCMDG systems were constructed with systems comprising two and three components. The isotropic region was examined by visual inspection and confirmed using polarized light microscopy. Viscosities of formulations were measured. The validated HPLC assay methods were developed for determination of levamisole and abamectin in liquid formulations and in sheep plasma. The HPLC assay was capable of evaluating stability of abamectin and levamisole in liquid formulations. Solubilities of levamisole hydrochloride or levamisole phosphate and abamectin were determined in the isotropic MCMDG formulations using a HPLC assay method. Stabilities of levamisole phosphate and abamectin were conducted in the isotropic MCMDG formulations at 60�C for 10 days. In vitro release studies for levamisole phosphate were carried out for selected formulations using modified Franz diffusion cells. Based on stability and in vitro release studies, one formulation (MCMDG/propylene glycol (PG):glycerol formal (GF), 20/20:60 % w/w) was selected for a preliminary in vivo study. The selected MCMDG/PG:GF (20/20:60) formulation containing both levamisole phosphate and abamectin was injected subcutaneously into sheep, and the injection site was examined after subcutaneous injection. Pharmacokinetic profiles were determined. A correlation between in vitro fraction released (FR) and in vivo fraction absorbed (FA) for levamisole phosphate from the MCMDG/PG:GF (20/20:60) formulation was assessed. Results: The isotropic systems of the MCMDG systems containing two or three components were characterized through phase diagrams and viscosity. The solubility of the levamisole hydrochloride in the isotropic MCMDG/sesame oil/water formulations was higher in the absence of abamectin than in combination with abamectin. Solubility of levamisole phosphate was higher in the MCMDG system containing GF or PG compared to the MCMDG/SO/water system. The isotropic MCMDG/PG:GF systems allowed preparations of levamisole phosphate/abamectin solution dose forms containing more than the usual dosage of levamisole. Stability of both levamisole phosphate and abamectin in MCMDG/PG:GF formulations was higher compared with MCMDG/PG:GF/water formulations. Levamisole phosphate degraded in the presence or absence of abamectin in the MCMDG/PG:GF (20/20:60) formulation at 60�C for 10 days. Abamectin alone was found to be stable in the formulation at 60�C for 10 days. In vitro release of levamisole phosphate from water and the MCMDG formulations tested displayed first-order kinetics. Water from the receptor compartment was observed to pass through the membrane into the donor compartment. Therefore, an advancing layer of turbidity occurred in the donor phase. A highly significant decrease in release rate of levamisole phosphate was obtained in MCMDG/GP:GF (20/20:60) formulation compared to water and the other formulations. Pharmacokinetic studies of subcutaneous injection of MCMDG/PG:GF 20/20:60) formulation showed the tmax values of 2.2 h and 4.2 days for levamisole phosphate and abamectin, respectively. The Cmax was 0.94 [mu]g/ml for levamisole phosphate and 6.24 ng/ml for abamectin while the formulation displayed the AUC value was 5.2 [mu]g�h�ml⁻1 for levamisole phosphate and 84.7 ng�day�ml⁻1 for abamectin. No inflammatory reaction was observed at the injection site. Linear regression analysis showed that a significant relationship between the FR (in vitro) and FA for the subcutaneously injected formulation. Conclusion: The study carried out in this thesis introduces a new approach to formulating an injectable solution of the isotropic MCMDG/PG:GF systems containing both levamisole (hydrophilic drug) and abamectin (lipophilic drug) for subcutaneous administration, and presents the development of the HPLC assay methods for determination of levamisole and abamectin in liquid MCMDG formulations and plasma, in order to investigate in vitro and in vivo release from the isotropic MCMDG/PG:GF formulations. The MCMDG/PG:GF formulations may represent an alternative to the more traditional formulations for both lipophilic and hydrophilic drugs.