Water drug substance with

Solubilization is the increase in solubility of a poorly water-soluble substance with surface-active agents. The mechanism involves entrapment (adsorbed or dissolved) of molecules in micelles and the tendency of surfactants to form colloidal aggregations at critical micelle concentration levels. Thus, the critical micelle concentration is the minimum surfactant concentration that begins solubilization of the insoluble molecule. Increases in the concentration of micelles lead to increases in drug solubility. 

Two sensibly priced commercial databases for solubility exist [366,507], An article in the journal Analytical Profiles of Drug Substances carries solubility data [496]. Abraham and Le [508] published a list of intrinsic aqueous solubilities of 665 compounds, with many ionizable molecules. It is difficult to tell from published lists what the quality of the data for ionizable molecules is. Sometimes, it is not clear what the listed number stands for. For example, Sw, water solubility, can mean several different things either intrinsic value, or value determined at a particular pH (using buffers), or value measured by saturating distilled water with excess compound. In the most critical applications using ionizable molecules, it may be necessary to scour the original publications in order to be confident of the quality of reported values. 

Methoxypurine was found to crystallize as a hemihydrate from /V,/V -dimethyl formamide, and as a trihydrate from water [63]. Thermal treatment of the trihydrate could be used to obtain the hemihydrate. Zafirlukast was obtained in the form of monohydrate, methanol, and ethanol solvatomorphs, with the drug substance adopting a similar conformation in all three structures [64], In the isostructural methanol and ethanol solvates, the solvent molecules are hydrogen-bonded to two zafirlukast molecules, while in the monohydrate, the water molecules are hydrogen-bonded to three zafirlukast molecules. The structures of the acetone and isopropanol solvatomorphs of brucine have been reported, where the solvent controlled the self-assembly of brucine on the basis of common donor-acceptor properties [65],... 

Infrared (IR) spectroscopy, especially when measured by means of the Fourier transform method (FTIR), is another powerful technique for the physical characterization of pharmaceutical solids [17]. In the IR method, the vibrational modes of a molecule are used to deduce structural information. When studied in the solid, these same vibrations normally are affected by the nature of the structural details of the analyte, thus yielding information useful to the formulation scientist. The FTIR spectra are often used to evaluate the type of polymorphism existing in a drug substance, and they can be very useful in studies of the water contained within a hydrate species. With modem instrumentation, it is straightforward to obtain FTIR spectra of micrometer-sized particles through the use of a microscope fitted with suitable optics. 

PVA/p-CD/salicylic acid -p-CD forms inclusion complexes with different water soluble substances i.e. salicylic acid - The drug release from the PVA/p-CD gel is nearly proportional to time 235... 

The drug substance was a water-soluble base in salt form with a pK of about 9 that was also soluble in most organic solvents. The polymer in the tablet was, however, soluble only in an organic medium like methanol. Other organic solvents such as acetonitrile and dimethylformamide were... 

For autosampler precision, 10 consecutive lO-pL injections of an eth-ylparaben solution (20 J,g/mL) are used (Figure 6). A Waters Symmetry column packed with 5- J,m particles is used. The manufacturer s specification for peak area precision at 0.5% RSD is adopted as the acceptance criterion. This stringent precision criterion is required for precise assay testing of drug substances typically specified at 98-102% purity. The linearity test is performed by single injections of 5, 10, 40, and 80 pL of the... 

Some drug substances can form mesophases with or without a solvent [19-26]. In the absence of a solvent, an increase in temperature causes the transition from the solid state to the liquid crystalline state, called thermotropic mesomorphism. Lyotropic mesomorphism occurs in the presence of a solvent, usually water. A further change in temperature may cause additional transitions. Thermotropic and/or lyotropic liquid crystalline mesophases of drug substances may interact with meso-morphous vehicles as well as with liquid crystalline structures in the human organism. Table 1 presents drug substances for which thermotropic or lyotropic mesomorphism has been proved. 

Various techniques are used to reduce the amounts of these solvents left in the drug substance, such as washing with water to remove water-soluble solvents. 

Figure 1.4 Furosemide drug substance showing USP Compound B impurity together with other impurities. (Column 250 X 4.6 mm i.d. Phenomenex Luna (2) C-18 mobile-phase THE water acetic acid 35 65 O.I flow rate 1 ml/min detector UV 272 nm.)...

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