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Spray-dried dispersions (SDDs) of low-solubility drugs have been prepared using the polymer hydroxypropyl methylcellulose acetate succinate (HPMCAS). For a variety of drug structures, these SDDs provide supersaturation in in vitro dissolution determinations and large bioavailability increases in vivo. In bile-salt/lecithin in vitro solutions, these SDDs provide amorphous drug/polymer colloids and an increased concentration of free drug and drug in micelles relative to crystalline or amorphous drug. As dry powders, the SDDs are a single amorphous phase in which the drug remains amorphous and dispersed and does not crystallize over storage times relevant for practical drug products. A melting temperature (T m )/glass-transition temperature (T g ) (K/K) versus log P map for 139 compounds formulated as SDDs provides a perspective on an appropriate formulation strategy for low-solubility drugs with various physical properties.

We have measured whole-pulse photon statistics of macroscopic twin pulses of light generated by coherently seeding a two-mode optical parametric amplifier equally in each mode. We are able to produce 300 ps, near-transform-limited twin pulses ( -10^ photons) with a difference photon number having a variance measured to be 73% below the shot-noise level. We have measured probability distributions of the photoelectron difference number, which are the only photoelectron distributions in the macroscopic regime which cannot be explained using standard semiclassical detection theory.

The technique of dc-balanced, pulsed homodyne detection for the purpose of determining optical-field statistics on short time scales is analyzed theoretically. Such measurements provide photon-number and phase distributions associated with a repetitive signal light field in a short time window. Time-and space-varying signal and local-oscillator pulses are treated, thus generalizing earlier treatments of photoelectron difference statistics in homodyne detection. Experimental issues, such as the effects of imperfect detector balancing on (time-integrated) dc detection and the consequences of background noise caused by non-mode-matched parts of the multimode signal field, are analyzed. The Wigner, or joint, distribution for the two field-quadrature amplitudes during the sampling time window can be directly determined by tomographic inversion of the measured photoelectron distributions. It is pointed out that homodyne detection provides a new method for the simultaneous measurement of temporal and spectral information. Although the theory is generally formulated, with both signal and local-oscillator fields being quantized, emphasis is placed on the limit of a strong, coherent local-oscillator field, making semiclassical interpretation possible.

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