A comprehensive model of women's social cognition and responsiveness to infant crying: Integrating personality, emotion, executive function, and sleep.

Disparate lines of research suggest that women's (a) emotion regulation and personality, (b) executive function and (c) sleep may be important predictors of mothers' cry responding in part through their effects on social cognition. However, the extent to which each contributes to cry responding independently remains unknown. We examined this question in a convenience sample of 109 nulliparous undergraduate women. Women completed online surveys to assess personality and emotion dysregulation traits, then visited the lab for a testing session during which they reported on sleep the night before and reactions to videotapes of crying infants and completed computerized working memory and inhibitory control tasks under challenging noise conditions (exposure to traffic and cry sounds). Results indicate that women's positive personality and higher working memory were associated with higher levels of infant-oriented cry processing (i.e., accurate distress detection, empathy and situational/emotional attributions about distress), which in turn was associated with higher intended responsiveness to infant crying. Emotion dysregulation and deficits in inhibitory control were associated with higher levels of self-oriented cry processing (i.e., anger, anxiety, negative and emotion minimizing attributions in response to infant distress), which in turn was associated with lower cry responsiveness. Short-term sleep deprivation was associated with lower intended responsiveness via the above path from poorer inhibitory control to heightened self-oriented cry processing. Findings suggest that sleep, emotional and cognitive factors are associated with cry processing and subsequent responsiveness independent of one another.

Effect of vehicle amphiphilicity on the dissolution and bioavailability of a poorly water-soluble drug from solid dispersions.

Solid dispersions of a poorly water-soluble drug [REV 5901; alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol; 1] in an amphiphilic vehicle [Gelucire 44/14; 2] and in polyethylene glycol (PEG) 1000, PEG 1450, and PEG 8000 were prepared. The vehicle 2 was a mixture of hydrogenated fatty acid esters with a mp of 44 degrees C, and had a HLB value of 14. Compound 1 was dissolved or dispersed in molten vehicles at elevated temperatures. The pulverization and compression of solid dispersions were avoided by encapsulating the hot solutions directly into hard gelatin capsules. At room temperature, the dispersions solidified forming plugs inside the capsules. On storage, greater than 180 mg of 1 remained dissolved per gram of vehicle, while the excess drug formed fine crystals (less than 20 micron). When mixed with water, the dissolved drug separated as a metastable liquid. Due to the surfactant property of 2, the oily form of 1 that separated from this vehicle formed an emulsified system with a globular size of less than 1 micron, while greater than 80% of 1 that separated from the other three formulations coalesced to form large oily masses. As a result of the large difference in surface area, the dissolution rate of 1 in simulated gastric fluid from capsules containing 2 was much higher than that of a PEG-based formulation. The bioavailability (AUC) of 1 in dogs from capsules containing 2 was also higher than that from PEG 1000-based capsules.

Physicochemical basis of increased bioavailability of a poorly water-soluble drug following oral administration as organic solutions.

The physicochemical basis of improvement of the bioavailability of a poorly water-soluble drug [REV 5901; alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol; 1] after oral administration as organic solutions was investigated. The drug, which exists in solid and metastable liquid forms, had a pKa value of 3.7 and a solubility of approximately 0.002 mg/mL in water (pH approximately 6) at 37 degrees C. It had appreciable aqueous solubility only at pH values less than 2. The dissolution rate of 1 at pH values greater than 3 was practically zero. On dilution of the water-miscible organic solutions (polyethylene glycol 400 and polysorbate 80) of 1 with aqueous media, the drug instantaneously formed saturated solutions and the excess drug separated as emulsified oily globules. The dispersibility of the globules improved in the presence of surfactants. The average globule size of the oily form of 1 was 1.6 micron or less, as compared with a particle size of 5-10 microns for the solids. Thus, a high surface area of 1 was obtained after oral intake of water-miscible organic solutions. Although 1 was practically insoluble under intestinal pH conditions, its solubility was greatly increased in the presence of bile salts, lecithin, and lipid-digestion mixtures. The high surface area of 1 separating from organic solutions would facilitate its dissolution rate in the presence of biological surfactants and lipids and, therefore, would increase its bioavailability.

Common ion effect on solubility and dissolution rate of the sodium salt of an organic acid.

The solubility and the dissolution rate of the sodium salt of an acidic drug (REV 3164; 7-chloro-5-propyl-1H,4H-[1,2,4]triazolo[4,3-alpha]quinoxaline-1,4-dione) decreased by the effect of common ion present in aqueous media. The solubility of the sodium salt of REV 3164 in a buffered medium was much lower than that in an unbuffered medium. Also, the presence of NaCl decreased its solubility in water. The apparent solubility product (K'sp) of the salt, however, did not remain constant when the concentration of NaCl was changed. A decrease in K'sp value with the increase in NaCl concentration was observed; for example, the K'sp values at 0 and 1 M NaCl were 7.84 X 10(-4) and 3.94 X 10(-4) M2, respectively. Even when corrected for the effect of ionic strength, the solubility product decreased. This decrease in the solubility product in the presence of NaCl indicated a decrease in the degree of self-association (increase in activity coefficient) of the drug in aqueous media.

Preformulation study of a poorly water-soluble drug, alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol: selection of the base for dosage form design.

The physicochemical properties of the base and hydrochloride salt of the poorly water-soluble drug alpha-pentyl-3-(2-quinolinylmethoxy) benzenemethanol (REV 5901) were investigated in order to select an appropriate form of the drug for dosage form development. The pH-solubility profiles of both the base and the salt at 37 degrees C were identical and were in agreement with a pKa value of 3.67 determined by the UV spectral method. The solubility of the drug (approximately 0.002 mg/mL at pH 6) increased gradually with a decrease in pH and reached a value of 0.95 mg/mL at pH 1; at pH values less than 1, the solubility decreased due to the common-ion effect. The pHmax, i.e., the pH of maximum solubility of the drug was, therefore, 1.0. The role of the pHmax in the selection of a salt or base form of a compound was investigated. Due to the conversion of the salt to the base at the surface of the dissolving solid at pH values greater than pHmax, the dissolution rates of both the base and the salt were identical. In the solid state, the salt existed in anhydrous and monohydrate forms; the anhydrous salt converted to the hydrate at greater than 40% relative humidity, and the hydrate lost water at 40-60 degrees C. The thermal properties of the salt were indicative of its potential instability, which was confirmed by accelerated stability studies. The base existed in a stable crystalline solid form, and also in an oily liquid form which converted to crystals on standing.(ABSTRACT TRUNCATED AT 250 WORDS)

Water migration from soft gelatin capsule shell to fill material and its effect on drug solubility.

The bioavailability of some poorly water-soluble drugs was reported to increase due to a change in dosage form from a tablet to a solution encapsulated in soft gelatin capsules. However, the objective of increasing the bioavailability may be defeated if the drug crystallizes from a solution inside the capsule. In this study, a water-insoluble drug [alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol; REV 5901] was solubilized in both polyethylene glycol 400 (PEG 400) and a 6:1 mixture of Gelucire 44/14:PEG 400. The solutions were then encapsulated in soft elastic gelatin capsules with a fill weight of 700 mg (drug, 125 mg), and water migration from the capsule shell into the fill material and its effect on the solubility of the drug were investigated. Gelucire 44/14 is a mixture of hydrogenated fatty acid esters with a mp of 44 degrees C; PEG 400 was added to reduce the mp of solution to approximately 36 degrees C for easier encapsulation. After equilibration of capsules at ambient condition, the amount of water in the PEG 400 solution was 6.3%. This reduced the solubility of the drug by 45%, resulting in drug crystallization. The solubility decreased exponentially with the increase in water content. The water in the encapsulated Gelucire:PEG solution was only 1.1%, which did not affect the solubility significantly.

Evaluation of topical anti-inflammatory steroid formulations in an Arthus model of inflammation.

Formulations of a number of steroids were evaluated after topical application in a reversed passive Arthus test (RPA) in rabbits. Four 21-chlorosteroids in the same cream base were investigated. The preparations of SQ 18,566 (halcinonide) and SQ 20,811 showed anti-edema activity, but those of SQ 15,361 and SQ 20,589 were less active. Ointment formulations of halcinonide also reduced edema in the RPA. These results, coupled with previously reported clinical data, suggest that the RPA might be utilized to distinguish good from poor formulations of anti-inflammatory steroids prior to screening tests or clinical trials in humans.