Simon Lowes, Iain S. Haslam, Britt-Marie Fihn, Constanze Hilgendorf, Johan E. Karlsson, Nicholas L. Simmons and Anna-Lena Ungell
Article: The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat
Pharmaceutics 2010, 2(1), 61-77; doi:10.3390/pharmaceutics2010061 - published online 15 March 2010
Show/Hide AbstractAbstract: The effect of Pgp induction in rats by pregnenolone 16α-carbonitrile (PCN) (3 days, 35 mg/kg/d, p.o.) on digoxin pharmacokinetics and intestinal transport has been assessed. After intravenous or oral digoxin dosing the arterial and hepatic portal vein (oral) AUC_(0-24h) were significantly reduced by PCN pre-treatment. Biliary digoxin clearance increased 2-fold following PCN treatment. PCN significantly increased net digoxin secretion (2.05- and 4.5-fold respectively) in ileum and colon but not in duodenum or jejunum. This increased secretion correlated with increased Pgp protein expression in ileum and colon. Both intestinal and biliary excretion therefore contribute to altered digoxin disposition following PCN.

Connie M. Remsberg, Renee L. Good and Neal M. Davies
Article: Ingredient Consistency of Commercially Available Polyphenol and Tocopherol Nutraceuticals
Pharmaceutics 2010, 2(1), 50-60; doi:10.3390/pharmaceutics2010050 - published online 8 March 2010
Show/Hide AbstractAbstract: Label claims of vitamin E succinate and polyphenolic nutraceuticals are assessed. A validated HPLC method was utilized to assess vitamin E succinate products. Three novel LC/MS methods were used to assess the polyphenols, pterostilbene, phloretin, and myricetin, in dietary supplements. The amount of vitamin E succinate varied from 0-130% of the stated label content with two products containing vitamin E acetate rather than vitamin E succinate. Expected polyphenols were found in 7 of the 8 supplement products. None of the polyphenol supplements contained content within 100-120% of label claims. The present study indicates a lack of uniformity in nutraceutical products.

Ulrike Zimper, Jaakko Aaltonen, Cushla M. McGoverin, Keith C. Gordon, Karen Krauel-Goellner and Thomas Rades
Article: Quantification of Process Induced Disorder in Milled Samples Using Different Analytical Techniques
Pharmaceutics 2010, 2(1), 30-49; doi:10.3390/pharmaceutics2010030 - published online 16 February 2010
Show/Hide AbstractAbstract: The aim of this study was to compare three different analytical methods to detect and quantify the amount of crystalline disorder/ amorphousness in two milled model drugs. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Raman spectroscopy were used as analytical methods and indomethacin and simvastatin were chosen as the model compounds. These compounds partly converted from crystalline to disordered forms by milling. Partial least squares regression (PLS) was used to create calibration models for the XRPD and Raman data, which were subsequently used to quantify the milling-induced crystalline disorder/ amorphousness under different process conditions. In the DSC measurements the change in heat capacity at the glass transition was used for quantification. Differently prepared amorphous indomethacin standards (prepared by either melt quench cooling or cryo milling) were compared by principal component analysis (PCA) to account for the fact that the choice of standard ultimately influences the quantification outcome. Finally, the calibration models were built using binary mixtures of crystalline and quench cooled amorphous drug materials. The results imply that the outcome with respect to crystalline disorder for milled drugs depends on the analytical method used and the calibration standard chosen as well as on the drug itself. From the data presented here, it appears that XRPD tends to give a higher percentage of crystalline disorder than Raman spectroscopy and DSC for the same samples. For the samples milled under the harshest milling conditions applied (60 min, sixty 4 mm balls, 25 Hz) a crystalline disorder/ amorphous content of 44.0% (XRPD), 10.8% (Raman spectroscopy) and 17.8% (DSC) were detected for indomethacin. For simvastatin 18.3% (XRPD), 15.5% (Raman spectroscopy) and 0% (DSC, no glass transition) crystalline disorder/ amorphousness were detected.

Irene Zagol-Ikapitte, Elena Matafonova, Venkataraman Amarnath, Christopher L. Bodine, Olivier Boutaud, Rommel G. Tirona, John A. Oates, L. Jackson Roberts II and Sean S. Davies
Article: Determination of the Pharmacokinetics and Oral Bioavailability of Salicylamine, a Potent γ-Ketoaldehyde Scavenger, by LC/MS/MS
Pharmaceutics 2010, 2(1), 18-29; doi:10.3390/pharmaceutics2010018 - published online 1 February 2010
Show/Hide AbstractAbstract: Levels of reactive γ-ketoaldehydes derived from arachidonate increase in diseases associated with inflammation and oxidative injury. To assess the biological importance of these γ-ketoaldehydes, we previously identified salicylamine as an effective γ-ketoaldehyde scavenger in vitro and in cells. To determine if salicylamine could be administered in vivo, we developed an LC/MS/MS assay to measure salicylamine in plasma and tissues. In mice, half-life (t_1/2) was 62 minutes. Drinking water supplementation (1-10 g/L) generated tissue concentrations (10-500 μM) within the range previously shown to inhibit γ-ketoaldehydes in cells. Therefore, oral administration of salicylamine can be used to assess the contribution of γ-ketoaldehydes in animal models of disease.

Farhan AlHusban, Amr M. ElShaer, Jiteen H. Kansara, Alan M. Smith, Liam M. Grover, Yvonne Perrie and Afzal R. Mohammed
Article: Investigation of Formulation and Process of Lyophilised Orally Disintegrating Tablet (ODT) Using Novel Amino Acid Combination
Pharmaceutics 2010, 2(1), 1-17; doi:10.3390/pharmaceutics2010001 - published online 4 January 2010
Show/Hide AbstractAbstract: Lyophilised orally disintegrating tablets (ODTs) have achieved a great success in overcoming dysphagia associated with conventional solid dosage forms. However, the extensive use of saccharides within the formulation limits their use in treatment of chronic illnesses. The current study demonstrates the feasibility of using combination of proline and serine to formulate zero sacharide ODTs and investigates the effect of freezing protocol on sublimation rate and tablets characteristics. The results showed that inclusion of proline and serine improved ODT properties when compared to individual counterparts. Additionally, annealing the ODTs facilitated the sublimation process and shortened the disintegration time.

Adamo Fini, Cristina Cavallari and Francesca Ospitali
Article: Effect of Ultrasound on the Compaction of Ibuprofen/Isomalt Systems
Pharmaceutics 2009, 1(1), 3-19; doi:10.3390/pharmaceutics1010003 - published online 9 October 2009
Show/Hide AbstractAbstract: Six mixtures, containing 10, 20 and 30% w/w ibuprofen and isomalt, were compacted by a traditional or ultrasound-assisted machine and analysed by means of thermal (DSC and TGA) and micro-spectrometry (Raman and FT-IR) techniques. Ultrasound discharge causes melting of ibuprofen powder, transforming into a paste that could not assume the shape of a tablet; when in mixture with isomalt, thermal events, occurring during ultrasound compaction, change the appearance of the particles formed by milling the tablets obtained this way and SEM photos reveal a dramatic reduction of the particle size and changes due to a possible ibuprofen re-crystallization. Raman and FT-IR spectra of small portions of the surface and of the bulk, using characteristic peaks for identification, reveal that in ultrasound-compacted tablets ibuprofen partially disappears from the top face of the tablet.