Browsing by Subject "Pharmaceutical compounds"
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Item An improved method for predicting logP(2006-08) Wu, Yubin, 1976-; Pearlman, Robert S.The logarithm of the octanol/water partition coefficient (logP) is used extensively as an indicator of hydrophobicity or lipophilicity within quantitative structure-activity relationships (QSARs) in the pharmaceutical, environmental, and other chemistry-related sciences. LogP is an important component of Lipinki’s “rule of 5” which is used throughout pharmaceutical industry to distinguish “drug-like” compounds from those likely to exhibit poor bioavailability. Using structure-based, calculated predictions of logP, rather than experimentally measured values, is of obvious advantage given the nearinfinite number of potential drug compounds and the relatively small number of compounds for which logP has been measured. MlogP is a simple yet useful structurebased method developed by Moriguchi et al. to estimate logP values. Moriguchi established rules for dividing molecular structures into 13 types of “fragments” and used measured logP values for 1,230 compounds to develop a regression equation based the frequencies with which each fragment occurred in the structure of each compound. Regrettably, Moriguchi’s description of his method is unclear in several respects. Lipinski implemented a program to calculate MlogP values but was forced to make certain assumptions regarding fragment definitions, etc. We will present a revised and definitive algorithm based on Moriguchi’s original concepts but developed using far more robust fragment definitions and statistical methods. The improved algorithm yields significantly better estimates for 6,529 “STARLIST” compounds with experimentally measured logP values.Item Supercritical fluid spray processes for microencapsulation and formation of submicron aqueous dispersions of pharmaceutical compounds(2003-12) Young, Timothy John; Johnston, Keith P., 1955-Precipitation with a Compressed Fluid Antisolvent (PCA) and Rapid Expansion from Supercritical Solution (RESS) are two processes based on supercritical fluids that are capable of producing submicron particles. Novel variations of these basic processes have been examined to produce stable particles of various pharmaceutical compounds. PCA is an antisolvent precipitation technique where an organic solution of drug + polymer in solvent is atomized (sprayed) into supercritical (SC) CO₂. Upon liquid mixing, the solute materials precipitate to form microparticles. A Vapor-over-Liquid technique has been used to produce larger, uniform particle sizes of biodegradable polymers. By suspending a protein in the solvent phase, the protein can be encapsulated/coated by the precipitating polymer. RESS is a process by which a homogeneous solution at supercritical conditions is sprayed through an expansion nozzle to atmospheric conditions. The resultant change in phase leads to the precipitation of the solute materials. The production of extremely small particles (<50 nm) have been predicted but rarely demonstrated. Typically, particle growth occurs to form larger (~1 μm) particles. A novel adaptation was developed, dubbed RESAS (Rapid Expansion from Supercritical to Aqueous Solution), wherein the expansion is conducted within an aqueous environment. The aqueous phase can contain surfactant or lipid stabilizers to capture and preserve submicron particles of water-insoluble drug actives in the form of a suspension.