Evaluation of tableting performance of Poly (ethylene oxide) in abuse-deterrent formulations using compaction simulation studies.

Poly (ethylene oxide) (PEO) has been widely used in abuse-deterrent formulations (ADFs) to increase tablet hardness. Previous studies have shown that formulation variables such as processing conditions and particle size of PEO can affect ADF performance in drug extraction efficiency. This work aims to understand the effect of PEO grades and sources on the compaction characteristics of model ADFs. PEOs from Dow Chemical and Sumitomo Chemical with different molecular weights were examined using a Styl'One compaction simulator at slow, medium, and fast tableting speeds. Particle-size distribution, thermal behavior, tabletability, compressibility using the Heckel model, compactibility, and elastic recovery were determined and compared between the neat PEOs and model ADFs. Multivariate linear regression was performed to understand the effect of compression conditions and PEO grades and sources. Our results show that neat PEOs with high molecular weight exhibit high tabletability. The source of neat PEOs contributes to the difference in tabletability, out-die compressibility, compactibility, and elastic recovery. However, the influence of the PEO source on tabletability and compactibility decreases after adding the model drug. In our model ADFs, tablets using PEOs with high molecular weight have high crushing strength, and tablets using PEOs from Dow Chemical display low elastic recovery.

Validated UHPLC-MS/MS method for quantification of doxycycline in abdominal aortic aneurysm patients.

AIM: There is a strong evidence that doxycycline can benefit abdominal aortic aneurysms patients because of its ability to inhibit matrix metalloproteinase enzymes. There is a need for a specific quantification method for doxycycline in these patients. We report herein the development and validation of a selective, specific, simple and rapid UHPLC-MS/MS method for doxycycline. RESULTS: The assay was linear (r2 > 0.994) over a concentration range of 0.010-7.005 µg/ml. This validated method has good lower limit of quantification (LLOQ) (10 ng/ml), accuracies (89.1-103.4%), precision (≤7.0%) and extraction recoveries (95.8%). Doxycycline was stable during short- and long-term storage. CONCLUSION: The assay is reliable and has been successfully applied to serum samples obtained from the patients of N-TA3CT clinical study.

LC-MS/MS assay for the determination of lurasidone and its active metabolite, ID-14283 in human plasma and its application to a clinical pharmacokinetic study.

The authors proposed a sensitive, selective and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay procedure for the quantification of lurasidone and its active metabolite, i.e. ID-14283 in human plasma simultaneously using corresponding isotope labeled compounds as internal standards as per regulatory guidelines. After liquid-liquid extraction with tert-butyl methyl ether, the analytes were chromatographed on a C18 column using an optimized mobile phase composed of 5 mm ammonium acetate (pH 5.0) and acetonitrile (15:85, v/v) and delivered at a flow rate of 1.00 mL/min. The assay exhibits excellent linearity in the concentration ranges of 0.25-100 and 0.10-14.1 ng/mL for lurasidone and ID-14283, respectively. The precision and accuracy results over five concentration levels in four different batches were well within the acceptance limits. Lurasidone and ID-14283 were found to be stable in battery of stability studies. The method was rapid with the chromatographic run time 2.5 min, which made it possible to analyze 300 samples in a single day. Additionally, this method was successfully used to estimate the in vivo plasma concentrations of lurasidone and ID-14283 obtained from a pharmacokinetic study in south Indian male subjects and the results were authenticated by conducting incurred samples reanalysis. Copyright © 2015 John Wiley & Sons, Ltd.