Journal of Pharmaceutical Analysis

Development of a physiologically relevant dripping analytical method using simulated nasal mucus for nasal spray formulation analysis$

Tina Masiuk n, Parul Kadakia, Zhenyu Wang

2016, 5(5): 283-291.

Abstract(68) PDF(4)

Abstract:
Current methods for nasal spray formulations have been elementary evaluating the dripping char-acteristics of a formulation and have not assessed the behavior of the nasal formulation in the presence of varying types of mucus depending on the indication or diseased state. This research investigated the effects of nasal mucus on the dripping behavior of nasal formulations and focused on developing an improved in vitro analytical test method that is more physiologically relevant in characterizing nasal formulation dripping behavior. Method development was performed using simulated nasal mucus preparations for both healthy and diseased states as coatings for the dripping experiment representing a wide range of viscosity. Factors evaluated during development of this in vitro test method included amount of mucus, application of mucus, drying times, and compatibility of the mucus on a C18 Thin Layer Chromatography (TLC) substrate. The dripping behavior of nasal formulations containing a range of 1%Avicel to 3.5%Avicel was assessed by actuating the nasal spray on a perpendicular TLC plate coated with either healthy or diseased simulated nasal mucus. After actuation of the nasal spray, the dripping of the formulation on the coated TLC plate was measured after the plate was repositioned vertically. The method that was developed generated reproducible results on the dripping behavior of nasal formula-tions and provided critical information about the compatibility of the formulation with the nasal mucus for different diseased states, aiding in nasal spray formulation development and physical characterization of the nasal spray.

Detection of phthalates migration from disposable tablewares to drinking water using hexafluoroisopropanol-induced catanionic surfactant coacervate extraction$

Cao Li, Jia Xu, Dan Chen, Yuxiu Xiao

2016, 5(5): 292-299.

Abstract(56) PDF(0)

Abstract:
Hexafluoroisopropanol (HFIP)-induced sodium dodecyl sulfate/dodecyltrimethylammonium bromide (SDS/DTAB) catanionic surfactant coacervate extraction method coupled with high performance liquid chromatography (HPLC) was used to detect the migration of phthalates from disposable tablewares to drinking water. The concentration factors are larger than 82 and extraction recoveries over 53%for water samples spiked with 100 or 200 ng/mL phthalates. Limit of detection is in the range of 1.0–2.6 ng/mL. Good linearity with correlation coefficients larger than 0.9985 is obtained in the concentration of 20–1500 or 40–3000 ng/mL. Relative recoveries are from 82.4%to 123.6%for water samples spiked with 30/60, 250/500, and 1500/3000 ng/mL phthalates, respectively. Relative standard deviations (RSDs) are 0.4%–7.4% for intraday precision (n ? 5) and 0.6%–7.8% for interday precision (n ? 3). Four of studied phthalates are found in the drinking water samples prepared from four kinds of tablewares.

Inclusion complexes of cefuroxime axetil withβ-cyclodextrin:Physicochemical characterization, molecular modeling and effect of L-arginine on complexation$

Sarika Sapte, Yogesh Pore

2016, 5(5): 300-306.

Abstract(56) PDF(0)

Abstract:
The inclusion complexes of poorly water-soluble cephalosporin, cefuroxime axetil (CFA), were prepared withβ-cyclodextrin (βCD) with or without addition of L-arginine (ARG) to improve its physicochemical properties. We also investigated the effect of ARG on complexation efficiency (CE) ofβCD towards CFA in an aqueous medium through phase solubility behaviour according to Higuchi and Connors. Although phase solubility studies showed AL (linear) type of solubility curve in presence and absence of ARG, the CE and association constant (Ks) ofβCD towards CFA were significantly promoted in presence of ARG, justifying its use as a ternary component. The solid systems of CFA withβCD were obtained by spray drying technique with or without incorporation of ARG and characterized by differential scanning ca-lorimetry (DSC), X-ray powder diffractometry (XRPD), scanning electron microscopy (SEM), and sa-turation solubility and dissolution studies. The molecular modeling studies provided a better insight into geometry and inclusion mode of CFA insideβCD cavity. The solubility and dissolution rate of CFA were significantly improved upon complexation withβCD as compared to CFA alone. However, ternary system incorporated with ARG performed better than binary system in physicochemical evaluation. In conclu-sion, ARG could be exploited as a ternary component to improve the physicochemical properties of CFA viaβCD complexation.

Analysis of residual crosslinking agent content in UV cross-linked poly(ethylene oxide) hydrogels for dermatological application by gas chromatography$

Rachel Shet Hui Wong, Mark Ashton, Kalliopi Dodou n

2016, 5(5): 307-312.

Abstract(107) PDF(0)

Abstract:
Acrylates have been widely used in the synthesis of pharmaceutical polymers. The quantitation of re-sidual acrylate monomers is vital as they are strong irritants and allergens, but after polymerization, are relatively inert, causing no irritation and allergies. Poly(ethylene oxide) (PEO) hydrogels were prepared using pentaerythritol tetra-acrylate (PETRA) as UV crosslinking agent. A simple, accurate, and robust quantitation method was developed based on gas chromatographic techniques (GC), which is suitable for routine analysis of residual PETRA monomers in these hydrogels. Unreacted PETRA was initially identi-fied using gas chromatography–mass spectrometry (GC–MS). The quantitation of analyte was performed and validated using gas chromatography equipped with a flame ionization detector (GC–FID). A linear relationship was obtained over the range of 0.0002%–0.0450% (m/m) with a correlation coefficient (r2) greater than 0.99. The recovery ( 4 90%), intra-day precision (%RSD o 0.67), inter-day precision (%RSD o 2.5%), and robustness (%RSD o 1.62%) of the method were within the acceptable values. The limit of detection (LOD) and limit of quantitation (LOQ) were 0.0001% (m/m) and 0.0002% (m/m), respectively. This assay provides a simple and quick way of screening for residual acrylate monomer in .

Pharmacokinetics of gene recombined angiogenesis inhibitor Kringle 5 in vivo using 131I specific markers and SPECT/CT$

Ge Yan, Danrong Yang, Yan Yu, Jianjun Xue, Yifan Jia, Xuanzi Sun, Boyu Wang, Zewei Zhao, Maode Wang

2016, 5(5): 313-317.

Abstract(56) PDF(0)

Abstract:
The previous pharmacokinetic methods can be only limited to drug analysis in vitro, which provide less information on the distribution and metabolismof drugs, and limit the interpretation and assessment of pharmacokinetics, the determination of metabolic principles, and evaluation of treatment effect. The objective of the study was to investigate the pharmacokinetic characteristics of gene recombination angiogenesis inhibitor Kringle 5 in vivo. The SPECT/CT and specific 131I-Kringle 5 marked by Iodogen method were both applied to explore the pharmacokinetic characteristics of 131I-Kringle 5 in vivo, and to investigate the dynamic distributions of 131I-Kringle 5 in target organs. Labeling recombinant angio-genesis inhibitor Kringle 5 using 131I with longer half-life and imaging in vivo using SPECT instead of PET, could overcome the limitations of previous methods. When the doses of 131I-Kringle 5 were 10.0, 7.5 and 5.0 g/kg, respectively, the two-compartment open models can be determined within all the metabolic process in vivo. There were no significant differences in t1/2α, t1/2β, apparent volume of distribution and CL between those three levels. The ratio of AUC(0 ? 1) among three different groups of 10.0, 7.5 and 5.0 g/kg was 2.56:1.44:1.0, which was close to the ratio (2:1.5:1.0). It could be clear that in the range of 5.0–10.0 g/kg, Kringle 5 was characterized by the first-order pharmacokinetics. Approximately 30 min after 131I-Kringle 5 was injected, 131I-Kringle 5 could be observed to concentrate in the heart, kidneys, liver and other organs by means of planar imaging and tomography. After 1 h of being injected, more radionuclide retained in the bladder, but not in intestinal. It could be concluded that 131I-Kringle 5 is mainly excreted through the kidneys. About 2 h after the injection of 131I-Kringle 5, the radionuclide in the heart, kidneys, liver and other organs was gradually reduced, while more radionuclide was concentrated in the bladder. The radionuclide was completely metabolized within 24 h, and the distribution of radioactivity in rats was similar to normal levels. In our study, the specific marker 131I-Kringle 5 and SPECT/CT were suc-cessfully used to explore pharmacokinetic characteristics of Kringle 5 in rats. The study could provide a new evaluation platform of the specific, in vivo and real-time functional imaging and pharmacokinetics for the clinical application of 131I-Kringle 5.

Isocoreopsin:An active constituent of n-butanol extract of Butea monosperma flowers against colorectal cancer (CRC)$

Boopathi Subramaniyan, Navaneethakrishnan Polachi, Ganeshan Mathan n

2016, 5(5): 318-325.

Abstract(108) PDF(0)

Abstract:
The herb Butea monosperma constitutes several human health beneficial components, which are mostly studied for their anticancer effects. In this study, the activity of n-butanol fractions of B. monosperma floral extract was examined on inhibiting aberrant crypt foci (ACF) formation in azoxymethane induced Wistar albino rats. The n-butanol extracts (150 mg/kg) decreased the ACF formation (per rat) by 92%and 78%in short-and long-term in vivo treatments, respectively. All the compounds in the n-butanol extract were isolated and purified using column and reverse-phase high pressure liquid chromatography (HPLC). Their structures were characterized using UV–visible spectroscopy, nuclear magnetic resonance (NMR) and electrospray–ionisation mass spectrometry (ESI–MS) to determine important flavonoids, namely isocoreopsin, butrin and isobutrin. These compounds were studied for their free radical scavenging and anticancer activities. The compound isocoreopsin showed significantly greater efficacy in cell death on human colon and liver cancer cell lines (50μg/mL in HT-29 and 100μg/mL in HepG2) than butrin (100μg/mL in HT-29 and 500μg/mL in HepG2) and isobutrin (80μg/mL in HT-29 and 150μg/mL in HepG2). These results suggest that isocoreopsin, butrin and isobutrin are the important key compounds for the chemoprevention of colon cancer and isocoreopsin can be considered as a promising novel drug.

A simple dilute and shoot methodology for the identification and quantification of illegal insulin$

Celine Vanhee n, Steven Janvier, Goedele Moens, Eric Deconinck, Patricia Courselle

2016, 5(5): 326-334.

Abstract(140) PDF(1)

Abstract:
The occurrence of illegal medicines is a well-established global problem and concerns mostly small molecules. However, due to the advances in genomics and recombinant expression technologies there is an increased development of polypeptide therapeutics. Insulin is one of the best known polypeptide drug, and illegal versions of this medicine led to lethal incidents in the past. Therefore, it is crucial for the public health sector to develop reliable, efficient, cheap, unbiased and easily applicable active pharma-ceutical ingredient (API) identification and quantification strategies for routine analysis of suspected il-legal insulins. Here we demonstrate that our combined label-free full scan approach is not only able to distinguish between all those different versions of insulin and the insulins originating from different species, but also able to chromatographically separate human insulin and insulin lispro in conditions that are compatible with mass spectrometry (MS). Additionally, we were also able to selectively quantify the different insulins, including human insulin and insulin lispro according to the validation criteria, put forward by the United Nations (UN), for the analysis of seized illicit drugs. The proposed identification and quantification method is currently being used in our official medicines control laboratory to analyze insulins retrieved from the illegal market.

Quantification of neomangiferin in rat plasma by liquid chromatography-tandem mass spectrometry and its application to bioavailability study$

Bo Yang, Zhirui Liu, Shenglan Shang, Xiaojian Qin, Peiyuan Xia

2016, 5(5): 335-340.

Abstract(60) PDF(0)

Abstract:
Neomangiferin, a natural C-glucosyl xanthone, has recently received a great deal of attention due to its multiple biological activities. In this study, a rapid and sensitive ultra-high performance liquid chroma-tography tandem mass spectrometry (UHPLC–MS/MS) method for the quantification of neomangiferin in rat plasma was developed. Using chloramphenicol as an internal standard (IS), plasma samples were subjected to a direct protein precipitation process using methanol (containing 0.05% formic acid). Quan-tification was performed by multiple reactions monitoring (MRM) method, with the transitions of the parent ions to the product ions of m/z 583.1-330.9 for NG and m/z 321.1-151.9 for IS. The assay was shown to be linear over the range of 0.2–400 ng/mL, with a lower limit of quantification of 0.2 ng/mL. Mean recovery of neomangiferin in plasma was in the range of 97.76%–101.94%. Relative standard deviations (RSDs) of intra-day and inter-day precision were both o 10%. The accuracy of the method ranged from 94.20%to 108.72%. This method was successfully applied to pharmacokinetic study of neomangiferin after intravenous (2 mg/kg) and intragastric (10 mg/kg) administration for the first time. The oral absolute bioavailability of neomangiferin was estimated to be 0.53%7 0.08%with an elimination half-life (t1/2) value of 2.74 7 0.92 h, indicating its poor absorption and/or strong metabolism in vivo.

Development and characterization of ethylcellulose based microsphere for sustained release of nifedipine$

Patitapabana Parida, Subash Chandra Mishra, Subhashree Sahoo, Ajit Behera, Bibhukalyan Prasad Nayak

2016, 5(5): 341-344.

Abstract(132) PDF(0)

Abstract:
This article introduced the work of ethylcellulose based polymeric microsphere loaded with nifedipine for reduction in frequency of administration with low solubility in aqueous medium and high rate of absorption in the stomach. The non-aqueous polymeric suspension was put dropwise into an aqueous medium containing polyvinyl alcohol as a surfactant for the synthesis of microsphere by solvent eva-poration. The microspheres were characterized by different techniques, namely, XRD, SEM, and NMR. The formation of microspheres was confirmed by SEM. XRD analysis revealed the semi-crystallinity nature of microspheres. The NMR study indicated the presence of hetero-aromatic nucleus in the microsphere.

Journal of Pharmaceutical Analysis

2016, 5(5): 345-346.

Abstract(80) PDF(0)

Abstract:

2016 Vol. 6, No. 5