Brief Report: Stability and Chemical Characteristics of Injectable Ascorbic Acid for Patients With Cancer.

CONTEXT: Intravenous ascorbic acid (IVAA) has been used extensively as part of the management plan for cancer patients in various medical clinics throughout the United States. The current research team has evaluated its effectiveness in patients with cancer as part of an ongoing research program. However, no data are available that support the chemical stability of intravenously injectable ascorbic acid (AA) to ensure its safety and efficacy in that patient population. Its clinical use as well as its use in research conducted in US Food and Drug Administration-approved clinical trials require validation of its stability. OBJECTIVE: The study intended to evaluate the chemical stability of the compounded IVAA that it prepares. DESIGN: The research team conducted a stability analysis within a 6-h period, a period longer than the time required for most infusions, which typically take approximately 2 h. The study evaluated the stability of AA intravenous sets, which are compounded solutions for clinical or hospital use. The IVAA was prepared in sterile water, together with magnesium chloride (MgCl) and calcium gluconate (CaGluc) as buffers. SETTING: The study took place at the Marcus Institute of Integrative Health at Thomas Jefferson University (Philadelphia, PA, USA). OUTCOME MEASURES: The study was performed for 2 dosages of an infusion set: 75 g and 100 g of IVAA. Interval testing included pH, particulate matter by light obscuration, and high-performance liquid chromatography assay. Analyses were performed at baseline and at 2-, 4-, and 6-h test intervals. RESULTS: The results demonstrated that IVAA remained highly stable throughout the 6-h period. It also passed the US Pharmacopeia's criteria for pH and particulates when used with a 0.2 µ filter. CONCLUSIONS: These data suggest that IVAA, when prepared with sterile water, in addition to MgCl and CaGluc, is highly stable and safe to use in patients for up to 6 h after preparation.

Investigation of the Physical, Chemical, and Microbiological Stability of Oral Solutions Compounded with Herbals.

The physical, chemical, and microbiological stability of a compounded oral solution with the active ingredients herbal tinctures of valerian and motherwort with sedative action for pediatric treatment was studied. Evaluations for physical, chemical, and microbiological stability were performed initially and throughout the storage period. Physical stability of the oral solution was assessed by coloration, clarity, and pH of the solution. The physical appearance of the oral solution did not change throughout the study period. The chemical stability of the oral solution was evaluated by means of a stability-indicating high-performance thin-layer chromatography analytical technique, identification tests, and assay method of sodium bromide. The microbiological stability of the oral solution was investigated by using the European Pharmacopoeia method using the acceptance criteria for nonsterile aqueous preparations for oral use. It was found that the compounded oral solution was stable for at least 21 days at 25°C ± 2°C/60% RH and 5°C ± 3°C, when protected from light.

Visual compatibility of colistin injection with other antibiotics during simulated Y-site administration.

PURPOSE: The compatibility of colistin with other antibiotics at concentrations commonly used in intensive care units was studied. METHODS: A vial of colistin was dissolved in sterile water for injection. The reconstituted solution (colistin base 75 mg/mL) was then diluted in 0.9% sodium chloride injection in polyvinyl chloride (PVC) infusion bag to give a total volume of 100 mL (colistin 1.5 mg/mL). Secondary drugs, including cefoperazone-sulbactam, ceftazidime, ertapenem, fosfomycin, imipenem-cilastatin, linezolid, meropenem, piperacillin-tazobactam, and vancomycin, were reconstituted if necessary and then diluted in 0.9% sodium chloride injection in PVC infusion bags to give final study concentrations of one-hundredth of their initial concentrations. The admixtures were collected in beakers at the end of the i.v. line and stored at 26 °C under constant fluorescent light throughout the study. Compatibility was assessed visually during delivery of each drug pair at time 0 and at 1 hour after starting the infusion. Compatibility was defined as the absence of visually detected particulate formation, haze, precipitation, color change, or gas evolution. Each combination was tested in triplicate. RESULTS: No particulate formation or other evidence of incompatibility was found in any of the studied drug combinations when observed immediately after mixing or at 1 hour. No particulate matter was observed with the unaided eyes, during microscopic evaluation, or against black and white backgrounds. CONCLUSION: Colistin 1.5 mg/mL was visually compatible with single concentrations of 9 other antimicrobial products during simulated Y-site injection at 26 °C without light protection for at least 1 hour.

Physical compatibility of tedizolid phosphate with selected i.v. drugs during simulated Y-site administration.

PURPOSE: The physical compatibility of commonly used agents that could be coadministered in the clinical setting with tedizolid phosphate during Y-site administration was evaluated. METHODS: Tedizolid phosphate vials were reconstituted to a final concentration of 0.8 mg/mL. All other drugs were prepared according to manufacturers' recommendations and diluted with 0.9% sodium chloride injection (where applicable) to the highest standard concentrations used clinically. Y-site conditions were simulated in culture tubes by mixing 5 mL of tedizolid phosphate solution with 5 mL of the test drug solutions. The physical characteristics, turbidity, and pH of all admixtures were examined immediately after mixing and at 15, 60, and 120 minutes. Incompatibility was defined as gross precipitation, a positive Tyndall beam test, color changes, or increases in turbidity. RESULTS: With simulated Y-site administration, tedizolid phosphate was compatible with 69 of 86 drugs in 0.9% sodium chloride injection, including 24 of 31 antimicrobial agents. Of note, incompatibility was observed immediately after mixing except with ceftaroline and diphenhydramine, whose incompatibility with tedizolid phosphate was apparent after 15 and 60 minutes, respectively. Among the drug classes tested, tedizolid phosphate was compatible only with 1 aminoglycoside (amikacin) and incompatible with 1 echinocandin (caspofungin) and 1 cephalosporin (ceftaroline). In addition, tedizolid phosphate was incompatible with divalent cations (calcium chloride, calcium gluconate, and magnesium sulfate), probably due to precipitation with the phosphate component. A pH change of >1 unit occurred only with epinephrine (at 120 minutes). CONCLUSION: Tedizolid phosphate 0.8 mg/mL in 0.9% sodium chloride injection was physically compatible with 69 of 86 study drugs during simulated Y-site administration.

Efficacy and Safety of Minoxidil 2% Solution in Combination With a Botanical Hair Solution in Women With Female Pattern Hair Loss/Androgenic Alopecia.

Female pattern hair loss (FPHL), also known as female androgenic alopecia, affects over 21 million women in the United States with devastating effects on self-esteem and psychosocial functioning. Topical minoxidil 2% and 5% formulations are the only US Food and Drug Administration-approved treatments for FPHL. The length of time it typically takes to observe the benefits is a challenge for many patients, and may affect adherence to treatment. Herbal extracts, which are also believed to promote healthier-looking hair, have a long history of use in hair care formulations. The safety and efficacy of a twice-daily regimen of 2% minoxidil solution used in combination with the botanical hair solution for 12 weeks in 54 subjects was evaluated in a multicenter, single-arm, open-label study. Assessments included investigator and subject ratings of improvement and subject satisfaction. Investigator ratings indicated significant improvement in hair growth and overall treatment benefits in as early as 6 weeks (P<.001). Subject self-ratings indicated significant satisfaction with hair volume and quality improvement at week 6 (P<.001). Subjects also indicated an increase in self-confidence and attractiveness at week 12 (P<.001). The investigator and subject-assessed efficacy and subject satisfaction with this regimen provides clinicians with an effective treatment option for FPHL that also provides a high level of patient acceptance, which ultimately may help promote minoxidil treatment adherence.

Efficacy and Safety of Minoxidil 5% Foam in Combination With a Botanical Hair Solution in Men With Androgenic Alopecia.

Androgenic alopecia (AGA) is the most common type of hair loss in men, characterized by hair miniaturization, hairline recession, and vertex balding. It affects approximately 50% of men, negatively affecting self-esteem and sociability. Topical minoxidil formulations are approved up to a 5% concentration for men, but patient adherence to treatment is challenged by gradual results that may be perceived as a lack of initial benefit. Herbal extracts, which are also believed to promote healthier-looking hair, have a long history of use in hair care formulations. The safety and efficacy of a twice-daily regimen of 5% minoxidil foam used in combination with a novel botanical hair solution was evaluated in a 12-week, multicenter, single-arm, open label study in 56 subjects with mild to moderate AGA. Assessments included investigator ratings of improvement and subject self-ratings of satisfaction. Investigator ratings indicated significant improvement in scalp hair coverage and perception of overall treatment benefit in as early as 4 weeks (P<.001). Subject self-ratings were significant for improved hair growth and hair appearance in as few as 4 weeks (P<.05). The regimen was well tolerated, and subjects indicated a high degree of satisfaction. Investigator and subject-assessed efficacy and subject satisfaction with this novel regimen provide clinicians with an effective treatment option for AGA that also provides a high level of patient satisfaction, which may help promote patient adherence to long-term treatment.

Toxicological evaluation of isopropylparaben and isobutylparaben mixture in Sprague-Dawley rats following 28 days of dermal exposure.

The alkyl esters of p-hydroxybenzoic acid (Parabens) have been of concern due to their probable endocrine disrupting property especially in baby consumer products. The safety of parabens for use as a preservative in cosmetics has come into controversy, and thus consumer demand for paraben-free products is ever increasing. Thus, more comprehensive studies are needed to conclusively determine the safety of the multiple prolonged exposure to parabens with cosmetic ingredients. This study was conducted to investigate the potential repeated 28 days dermal toxicity (50, 100, 300, or 600 mg/kg bw/day) of isopropylparaben (IPP), isobutylparaben (IBP), or the mixture of IPP and IBP in rats. There were no significant changes in body and organ weights in any group. However, histopathological examinations showed that weak or moderate skin damages were observed in female rats by macroscopic and microscopic evaluations. In female rats, no observed adverse effect levels (NOAELs) of IPP with no skin lesion and IBP for skin hyperkeratosis, were estimated to be 600 mg/kg bw/day, and 50 mg/kg bw/day, respectively. With regard skin hyperkeratosis, the lowest observed adverse effect level (LOAEL) of the mixture of IPP and IBP was estimated to be 50 mg/kg bw/day. Analysis of six serum hormones (estrogen, testosterone, insulin, T3, TSH, or FSH) in animals showed that only FSH was dose-dependently decreased in the mixture groups of 100 mg/kg bw/day or higher. These data suggest that the mixture of IPP and IBP showed a synergistic dermal toxicity in rats and should be considered for future use in consumer products.

Phase behavior of reverse microemulsions based on Peceol(®).

The phase diagram of the four component system Peceol®/lecithin/ethanol/water was studied at 25°C and at a fixed fraction of ethanol. It shows an isotropic W/O microemulsion phase, biphasic liquid system and Liquid crystalline phases. The stabilizing effect of lecithin with the fluidifying effect of ethanol on the microemulsion based on long chain glycerides provides an effective combination to solubilize a large amount of water. Some structural transitions in the phase diagram were investigated as a function of water content using conductivity, rheology, Karl Fisher titration, optical microscopy and SAXS measurements. The results show no change in the microstructure of the isotropic liquid upon phase separation in the liquid biphasic area. However, in the water rich region, migration of ethanol to the external aqueous phase at the expense of the saturated microemulsion promotes the formation of liquid crystalline phases. As a function of water content, the structural change to the liquid crystalline phases follows: isotropic phase L2 → Inverted hexagonal phase H2 → Inverted hexagonal H2/lamellar Lα phases.

[Simultaneous determination of six ingredients in Huoxiang Zhengqi oral liquid by UPLC].

OBJECTIVE: To develop a UPLC method for the simultaneous determination of liquiritin, narirutin, hesperidin, ammonium glycyrrhetate, honokiol and magnolol in Huoxiang Zhengqi oral liquid. METHOD: A Zorbax Eclipse C18 column was used with the mobile phase of acetonitrile and 0. 05% phosphate acid by gradient elution at the detection wavelength of 220 nm. The flow rate was 0.42 mL x min(-1) and the column temperature was 30 degrees C. RESULT: The calibration curves were linear in the ranges of 0.001 7-0.034, 0.003 4-0.068, 0.006 4-0.128, 0.012 8-0.256, 0.003 2-0.064, 0.006 4-0.128 microg, respectively. The average recoveries were 103.3%, 98.39%, 98.29%, 102.1%, 98.45%, 102.2% with RSDs of 2.1%,1.0%, 0.50%, 2.3%, 0.9%, 2.0%, respectively. CONCLUSION: The UPLC method was simple, rapid and accurate, it could be used for quality control of Huoxiang Zhengqi oral liquid.

Application of high-performance liquid chromatography with charged aerosol detection for universal quantitation of undeclared phosphodiesterase-5 inhibitors in herbal dietary supplements.

Incidents of detecting novel analogues of phosphodiesterase 5 (PDE-5) inhibitors in illicit dietary supplements for erectile dysfunction are constantly reported. However, little is known about their content in a single dose, mainly due to the poor availability or inaccessibility of pure reference standards. This study presents a new strategy of quantitative analysis of unknown and recently identified compounds. Charged aerosol detector (CAD), described as "universal detector", combined with high-performance liquid chromatography (HPLC) system proved to be a useful tool for fast and simple quantitation of PDE-5 inhibitors' analogues in a complex herbal matrix without individual reference standards available. Universal calibration was employed for calculations. Two easily obtainable reference materials - sildenafil and tadalafil - were selected as universal standards and the content of analogues was estimated with respect to their response. The error of proposed indirect determination was found to be ± 3%, which is less than enough to obtain a reliable result of the content. The elaborated method was applied for quantitative analyses of PDE-5 inhibitors and 10 analogues detected in 22 illicit dietary supplements and two bulk powdered herbal materials. All target analogues were identified using time-of-flight mass spectrometry with electrospray ionization. Obtained results indicate that the quantity of PDE-5 inhibitors in all tested samples is considered to be pharmacologically relevant.

Nanosized solvent superstructures in ultramolecular aqueous dilutions: twenty years' research using water proton NMR relaxation.

BACKGROUND: proton nuclear magnetic resonance (NMR) relaxation times T1, T2, T1/T2 are sensitive to motion and organization of water molecules. Especially, increase in T1/T2 reflects a higher degree of structuring. My purpose was to look at physical changes in water in ultrahigh aqueous dilutions. METHODS: Samples were prepared by iterative centesimal (c) dilution with vigorous agitation, ranging between 3c and 24c (Avogadro limit 12c). Solutes were silica-lactose, histamine, manganese-lactose. Solvents were water, NaCl 0.15 M or LiCl 0.15 M. Solvents underwent strictly similar, simultaneous dilution/agitation, for each level of dilution, as controls. NMR relaxation was studied within 0.02-20 MHz. RESULTS: No changes were observed in controls. Increasing T1 and T1/T2 were found in dilutions, which persisted beyond 9c (manganese-lactose), 10c (histamine) and 12c (silica-lactose). For silica-lactose in LiCl, continuous decrease in T2 with increase in T1/T2 within the 12c-24c range indicated growing structuring of water despite absence of the initial solute. All changes vanished after heating/cooling. These findings were interpreted in terms of nanosized (>4-nm) supramolecular structures involving water, nanobubbles and ions, if any. Additional study of low dilutions of silica-lactose revealed increased T2 and decreased T1/T2 compared to solvent, within the 10(-3)-10(-6) range, reflecting transient solvent destructuring. This could explain findings at high dilution. CONCLUSION: Proton NMR relaxation demonstrated modifications of the solvent throughout the low to ultramolecular range of dilution. The findings suggested the existence of superstructures that originate stereospecifically around the solute after an initial destructuring of the solvent, developing more upon dilution and persisting beyond 12c.

Simultaneous determination of synephrine, arecoline, and norisoboldine in Chinese patent medicine Si-Mo-Tang oral liquid preparation by strong cation exchange high performance liquid chromatography.

CONTEXT: Chinese patent medicine Si-Mo-Tang oral liquid preparation (SMT) is composed of Aucklandia luppa Decne (Compositae), Citrus aurantium Linn (Rutaceae), Lindera aggregata (Sims) Kosterm (Lauraceae), and Areca catechu Linn (Arecaceae). Studies of SMT have been impeded due to the lack of quality control methods. OBJECTIVE: This study aimed to simultaneously determine three alkaloids including synephrine, arecoline, and norisoboldine in SMT for the first time. MATERIALS AND METHODS: A strong cation exchange (SCX) high performance liquid chromatography (HPLC) method was developed to simultaneously determine synephrine, arecoline, and norisoboldine in SMT, and was compared with ion-pairing chromatography using regular reversed-phase chromatography columns. System suitability parameters of synephrine, arecoline, and norisoboldine using the SCX chromatography column were investigated. RESULTS: Results demonstrated that good separations were achieved on an Agilent SCX (250 × 4.6 mm, 5 µm) column at 35 °C. The mobile phase consisting of methanol-0.2% phosphoric acid was delivered at a constant flow of 1.0 mL min(-1) and the eluent was monitored at 215 nm. The HPLC method showed good linearity for the examined concentration ranges of 2.55-255.0, 1.30-208.0, and 2.06-201.6 µg mL(-1) for synephrine, arecoline, and norisoboldine, respectively. The limits of quantification (S/N = 10) were 2.55, 1.30, and 2.06 µg mL(-1), the limits of detection (S/N = 3) were 1.53, 0.78, and 1.21 µg mL(-1), and average recoveries were 98.99, 95.63 and 99.04%, respectively, for synephrine, arecoline, and norisoboldine. DISCUSSION AND CONCLUSION: This method has been successfully applied to determine synephrine, arecoline, and norisoboldine in Chinese patent medicine SMT.

In-line monitoring of alcohol precipitation by near-infrared spectroscopy in conjunction with multivariate batch modeling.

Alcohol precipitation is a critical unit operation during the manufacture of Chinese herbal injections. To facilitate enhanced process understanding and develop control strategy, the use of near-infrared spectroscopy (NIRS) combined with multivariate statistical process control (MSPC) methodology was investigated for in-line monitoring of alcohol precipitation. The effectiveness of the proposed approach was evaluated through an experimental campaign. Six batches were run under normal operating conditions to study batch-to-batch variation or batch reproducibility and establish MSPC control limits, while artificial process variations were purposefully introduced into the four test batches to assess the capability of the model for real-time fault detection. Several MSPC tools were compared and assessed. NIRS, in conjunction with MSPC, has proven to be a feasible process analytical technology (PAT) tool for monitoring batch evolution and potentially facilitating model-based advanced process control of the alcohol precipitation during the manufacture of Chinese herbal injections.

Preparation and characterization of shellac-coated anthocyanin pectin beads as dietary colonic delivery system.

SCOPE: Anthocyanins are connected with various biological activities. A promising way to enhance the availability of anthocyanins for in situ effects in the lower intestine is colon-specific delivery. METHODS AND RESULTS: Shellac and shellac/hydroxypropyl methylcellulose (HPMC) coated anthocyanin amidated pectin beads as dietary colonic delivery systems were successfully prepared by ionotropic gelation and fluid bed Wurster coating with aqueous shellac solution. Release characteristics, studied in vitro and ex vivo using simulated gastric fluid (SGF), ileostomy fluid and colostomy fluid (CF) revealed a retardation of anthocyanins during simulated passage of stomach and ileum as well as the desired release of pigments in the colon. Coating level was identified as an important parameter. By addition of 5 or 15% of the water-soluble polysaccharide HPMC to the shellac film, resistance in SGF was increased due to the plasticizer properties of the polymer. Incorporation of 15% HPMC (w/w based on shellac) into the shellac film additionally led to increased anthocyanin diffusivity and complete release as well as degradation of the formulation in CF. CONCLUSION: In the used in vitro and ex vivo model system mimicking the human intestinal transit, the potential of shellac and shellac/HPMC coated anthocyanin amidated pectin beads as dietary colon targeting systems was demonstrated.

Screening method for ethylene glycol and diethylene glycol in glycerin-containing products.

This paper describes a capillary gas chromatographic method with flame ionization detection for the identification/quantification of ethylene glycol (EG) and diethylene glycol (DEG) in glycerin. The validation study shows that the proposed method is specific, sensitive, precise, and accurate. The linear range of the method was 0.013-0.031mg/mL for EG and 0.012-0.030mg/mL for DEG. Wider ranges may be achievable but were not investigated. The limit of detection of EG and DEG were determined as 0.0018% and 0.0036% (w/w) respectively, and at this concentration the signal-to-noise ratios for EG and DEG were approximately 3:1. The method was also used to determine EG and DEG in toothpaste. The results were compared to those obtained by thin-layer chromatography (TLC) and showed greater sensitivity and specificity.

[The determination of aristolochic acid A in different processed Aristolochia manshuriensis and the test of influence about renal function in rats].

OBJECTIVE: To study and approach the processing methods and mechanism which can markedly reduce the content of aristolochic acid in Aristolochia manshuriensis and lighten the nephrotoxicity of aristolochic acid. METHODS: A traditional "attenuation" processing method was used and 30 types of samples which contain one crude and 29 types of processed sample were obtained. The contents of aristolochic acid A in every sample were determined by HPLC. According to the Rat's acute renal injury test, the influence of animal's renal function was investigated for representative samples. RESULTS: The content of aristolochic acid in six types of samples depressed markedly (30% or more depressed) which processing with boiling in the limewater, steaming with limewater, boiling in the juice of liquorice, boiling in the decoction of black soybean, boiling in the soda water and stir-baked with talcum powder, the content of aristolochic acid in other processed samples also depressed with a large discrepancy. The toxicology test results showed that the above-mentioned 6 samples all can relieve renal injury of rats. There could be some associativity between the degree of renal injury relieving and the content of aristolochic acid A in the samples. CONCLUSION: The content of aristolochic acid can be reduced and the nephrotoxicity for animals can be lightened with some eligible processing methods for the traditional Chinese medicines containing aristolochic acid with the representative of Aristolochia manshuriensis.

Visual compatibility of i.v. medications routinely used in bone marrow transplant recipients.

PURPOSE: The visual compatibility of i.v. medications routinely used in bone marrow transplant recipients was studied. METHODS: A total of 17 drug combinations were tested using simulated Y-site administration. Medications were prepared to the standard concentrations used at University of Utah Health Care and infused at the appropriate rate. For each combination, the two drugs had 99 cm of shared tubing. At the end of the shared tubing was a 0.8-microm filter disk. All of the drug combinations were tested in triplicate. After the infusion was complete, each filter was bubble-point tested to ensure filter integrity and to remove residual solution. The tubing and dried filter were examined by eye as well as a magnification microscope. Drug combinations were considered incompatible if a precipitate or color change was visible to the naked eye during filtration or if the number of particles observed under the microscope exceeded 12 particles of > or =10 microm in diameter per milliliter of solution or if 2 or more particles of > or =25 microm in diameter per milliliter of solution were observed, per guidelines established by the United States Pharmacopeia for large-volume injections. RESULTS: Of the 17 drug combinations tested, 5 combinations were observed to be visually incompatible. All of the incompatible combinations included acyclovir as the primary infusion. Acyclovir was incompatible with cyclosporine, diphenhydramine, gentamicin, granisetron, and metoclopramide. CONCLUSION: Of the 17 drug combinations tested, 5 combinations were observed to be visually incompatible during simulated Y-site injection. The combinations found to be visually incompatible included acyclovir with cyclosporine, diphenhydramine, gentamicin, granisetron, or metoclopramide.

Formulation and evaluation of taste masked oral reconstitutable suspension of primaquine phosphate.

The purpose of this research was to mask the intensely bitter taste of primaquine phosphate (PRM) and to formulate suspension powder (cachets) of the taste masked drug. Taste masking was done using beta-cyclodextrin. To characterize and formulate taste masked cachets of PRM, the 1:25 M physical mixture was selected based on bitterness score. Phase solubility studies, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD) were performed to identify the physicochemical interaction between drug and carrier, hence its effect on dissolution. Cachets were evaluated for angle of repose, sedimentation characterization and pH. In vitro drug release studies for physical mixture and kneaded system were performed at pH, 1.2 and 6.8. Bitterness score was evaluated using gustatory sensation test. Phase solubility studies showed weak interaction between PRM and CD. The FTIR, DSC and XRPD studies indicated inclusion complexation in physical mixture and kneaded system. In addition, kneaded system and physical mixture exhibited better drug release at pH 1.2 and negligible effect at pH 6.8. Cachets prepared using physical mixture, (DS24), showed complete bitter taste masking and easy redispersibility. Taste evaluation of cachets in human volunteers rated tasteless with a score of 0 to DS24 and 3 to DS25. Thus, results conclusively demonstrated successful taste masking and formulation of cachets with taste masked drug.

Modeling free energies of solvation in olive oil.

Olive oil partition coefficients are useful for modeling the bioavailability of drug-like compounds. We have recently developed an accurate solvation model called SM8 for aqueous and organic solvents (Marenich, A. V.; Olson, R. M.; Kelly, C. P.; Cramer, C. J.; Truhlar, D. G. J. Chem. Theory Comput. 2007, 3, 2011) and a temperature-dependent solvation model called SM8T for aqueous solution (Chamberlin, A. C.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B 2008, 112, 3024). Here we describe an extension of SM8T to predict air-olive oil and water-olive oil partitioning for drug-like solutes as functions of temperature. We also describe the database of experimental partition coefficients used to parametrize the model; this database includes 371 entries for 304 compounds spanning the 291-310 K temperature range.

Preparing botanical medicines.

Next to dose concerns, the subject of preparation may be the most misinterpreted area of modem botanical medicine. Yet it is one of the most important issues in clinical practice. In traditional medicine systems, any given herb would have been discovered to be effective in specific preparations. The "ideal" form and preparation varies from herb to herb, as well as from person to person. The most desirable preparation is usually defined as the way to get the most active ingredient out of the herb. However, in some cases, the proper preparation may be the only way to safely use the herb. The proper preparation may be dictated by the solubility of the constituents and may also be defined according to how the patient is practicably able to consume it. In today's market, most herbs can be found in most preparations, but that does not mean that every preparation will contain active constituents. The author makes the case that using traditional preparations from the ethnic system of the herb origin will be the most effective clinical course of action.