• A longitudinal study of United Kingdom pharmacists' misdemeanours--trials, tribulations and trends.

      Tullett, Julie; Rutter, Paul M.; Brown, David (Springer Verlag, 2003)
      BACKGROUND: Standards of UK pharmacy practice are maintained by the Royal Pharmaceutical Society of Great Britain, which has the power to take a range of sanctions, including removal of the right to practice, against those found guilty of malpractice. This function is currently under review. OBJECTIVE: To conduct a longitudinal study in order to define trends and identify areas where remedial or preventative support could be focused. METHOD: Case analysis of reports of individuals' misdemeanours published in the British Pharmaceutical Journal over a 12-year period (September 1988-October 2000). Professional and personal misdemeanours were considered. MAIN OUTCOME MEASURE: Nature of misdemeanour, conviction or disciplinary proceedings against individual, practising pharmacists in the study period. Reasons offered for committing the misdemeanour and penalties applied. RESULTS: 344 cases, involving a wide range of personal (162) and professional (590) misdemeanours were found. On an annual basis, the maximum incidence of pharmacists found guilty of any misdemeanour was extremely low (< 0.1 of 1% on the pharmaceutical register). The most common professional misdemeanour was failure to keep adequate written records. The most common personal misdemeanour was fraud. The most common reason cited for committing any misdemeanour was financial gain. Numbers in individual offence categories were persistent but low and there were few obvious trends with time. The odds of involvement ratio for male versus female pharmacists was 7.36 (CI: 5.23-10.35) and for ethnic minority versus Caucasian pharmacists was 3.8 (CI: 3.06-4.72). The most stringent penalties (either imprisonment or removal of the right to practice and frequently both) were applied to cases involving personal use or trafficking of drugs subject to abuse. CONCLUSIONS: The current self-regulation of pharmacy practice in the UK involves a wide range of misdemeanours of varying severity; but the incidence of reports of pharmacists found guilty of malpractice was extremely low. The nature of misdemeanours appeared to change little over the period of the study; this study therefore indicates the spectrum of misdemeanours likely to be encountered by a regulating board in the immediate to medium-term future. If regulatory changes such as competence-based practice rights are introduced, the spectrum may change.
    • A methodological evaluation and predictive in silico investigation into the multi-functionality of arginine in directly compressed tablets

      ElShaer, Amr; Kaialy, Waseem; Akhtar, Noreen; Iyire, Affiong; Hussain, Tariq; Alany, Raid; Mohammed, Afzal R. (Elsevier, 2015-10)
      The acceleration of solid dosage form product development can be facilitated by the inclusion of excipients that exhibit poly-/multi-functionality with reduction of the time invested in multiple excipient optimisations. Because active pharmaceutical ingredients (APIs) and tablet excipients present diverse densification behaviours upon compaction, the involvement of these different powders during compaction makes the compaction process very complicated. The aim of this study was to assess the macrometric characteristics and distribution of surface charges of two powders: indomethacin (IND) and arginine (ARG); and evaluate their impact on the densification properties of the two powders. Response surface modelling (RSM) was employed to predict the effect of two independent variables; Compression pressure (F) and ARG percentage (R) in binary mixtures on the properties of resultant tablets. The study looked at three responses namely; porosity (P), tensile strength (S) and disintegration time (T). Micrometric studies showed that IND had a higher charge density (net charge to mass ratio) when compared to ARG; nonetheless, ARG demonstrated good compaction properties with high plasticity (Y = 28.01 MPa). Therefore, ARG as filler to IND tablets was associated with better mechanical properties of the tablets (tablet tensile strength (r) increased from 0.2 ± 0.05 N/mm2 to 2.85 ± 0.36 N/mm2 upon adding ARG at molar ratio of 8:1 to IND). Moreover, tablets’ disintegration time was shortened to reach few seconds in some of the formulations. RSM revealed tablet porosity to be affected by both compression pressure and ARG ratio for IND/ARG physical mixtures (PMs). Conversely, the tensile strength (r) and disintegration time (T) for the PMs were influenced by the compression pressure, ARG ratio and their interactive term (FR); and a strong correlation was observed between the experimental results and the predicted data for tablet porosity. This work provides clear evidence of the multi-functionality of ARG as filler, binder and disintegrant for directly compressed tablets.
    • A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

      Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antzack, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J; Guindani, Michele; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco (Public Library of Science (United States), 2016-04)
      The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks in a wide spectrum of biological systems.
    • A novel sensing technique for measurement of magnitude and polarity of electrostatic charge distribution across individual particles.

      Hussain, Tariq; Kaialy, Waseem; Deng, Tong; Bradley, Mike S A; Nokhodchi, Ali; Armour-Chélu, David (Elsevier, 2013-01-30)
      Electrostatic charge is generated during powder handling due to particle-particle and particle-wall collisions, rubbing, sliding, and rolling. In case of bipolar charge generation, the electrostatic forces may significantly change the inner forces and increase powder adhesion and cause a serious problem in material handling process. Therefore, the knowledge of distribution of charge across the individual particles is helpful to identify the role of triboelectrification and the effects of various relevant variables especially change in the contact materials, environmental conditions during processing, etc. A novel approach based on inductive sensor has been developed to detect the either polarity of charged particle and to characterise the bipolar charge distribution in the population of particulate material. To achieve this, an amplification unit configured as a pure integrator and signal processing techniques has been used to de-noise and correct the baseline of signal and MATLAB algorithm developed for peak detection. The polarity of charged particles obtained by this method is calibrated with Faraday pail method and the results are promising. Experimental study has been carried out by using two distinct populations of oppositely charged particles (glass beads-PVC, olivine sand, and silica sand). The obtained results indicate that the method is able to detect the distribution of polarities of charged particles.
    • A panel study on the effects of a Chinese medicinal suppository, Vigconic VI-28, on insulin-like growth factor 1 and homocysteine in healthy men

      Chui, Siu-Hon; Chan, Kelvin C.; Wong, Ricky N. S.; Chen, K.J. (Prous Science, 2004)
      Changes in serum homocysteine (Hcy), often related to stroke and vascular dementia, are negatively correlated with changes in serum insulin-like growth factor 1 (IGF-1) and growth hormone (GH) replacement decreases Hcy levels in men with GH deficiency. Very little information on the effects of Chinese medicines on GH and Hcy is available in the literature published in English. In this study, the effects of a Chinese medicine suppository, Vigconic VI-28 (VI-28), consisting of concentrated extracts of a composite mixture of herbal materials, on serum IGF-1 and Hcy were studied. In vivo observations after treatment with Chinese medicines have often indicated changes in biochemical profiles of measurable parameters related to those changes in endocrine secretions. Thirty six healthy males (age 47-66) were under observation over a 16-week schedule after using VI-28 suppository from 0 to 12 weeks. Blood specimens were taken monthly (except at the end of week 8) for analysis of Hcy and IGF-1 levels. Compared with week 0, IGF-1 levels (192.5 ± 66.4 ng/ml) were significantly elevated at week 4 (211.7 ± 80.5, p < 0.05) and week 12 (226.6 ± 95.2 ng/ml, p = 0.01). No significant changes were observed for Hcy for the whole cohort from week 0 to week 16. When the cohort was divided into 2 groups using a Hcy level of 13.0 µmol/l as the cut-off, a significant (p < 0.05) difference in IGF-1 was observed between the 2 groups at week 12 only. The mean IGF-1 of 14 subjects with higher Hcy levels was lower than that of the 22 subjects with lower Hcy. We believe that VI-28 may exert a regulatory effect on the relationship between Hcy and IGF-1, at least in subjects with relatively low levels of Hcy. In addition, we also observed an apparent association of hyperhomocysteinemia (Hcy greater than or equal to 13.0 mcmol/l) with decreased IGF-1.
    • An Investigation on the Effect of Polyethylene Oxide Concentration and Particle Size in Modulating Theophylline Release from Tablet Matrices.

      Shojaee, Saeed; Emami, Parastou; Mahmood, Ahmad; Rowaiye, Yemisi; Dukulay, Alusine; Kaialy, Waseem; Cumming, Iain; Nokhodchi, Ali (Springer, 2015-03-14)
      Polyethylene oxide has been researched extensively as an alternative polymer to hydroxypropyl methylcellulose (HPMC) in controlled drug delivery due to its desirable swelling properties and its availability in a number of different viscosity grades. Previous studies on HPMC have pointed out the importance of particle size on drug release, but as of yet, no studies have investigated the effect of particle size of polyethylene oxide (polyox) on drug release. The present study explored the relationship between polymer level and particle size to sustain the drug release. Tablets produced contained theophylline as their active ingredient and consisted of different polyethylene oxide particle size fractions (20-45, 45-90, 90-180 and 180-425 μm). It was shown that matrices containing smaller particle sizes of polyox produced harder tablets than when larger polyox particles were used. The release studies showed that matrices consisting of large polyox particles showed a faster release rate than matrices made from smaller particles. Molecular weight (MW) of the polymer was a key determining step in attaining sustained release, with the high MW of polyox resulting in a delayed release profile. The results showed that the effect of particle size on drug release was more detrimental when a low concentration of polyox was used. This indicates that care must be taken when low levels of polyox with different particle size fractions are used. More robust formulations could be obtained when the concentration of polyox is high. Differential scanning calorimetry (DSC) traces showed that particle size had no major effect on the thermal behaviour of polyox particles.
    • Antisolvent crystallisation is a potential technique to prepare engineered lactose with promising aerosolisation properties: effect of saturation degree.

      Kaialy, Waseem; Nokhodchi, Ali (Elsevier, 2012-11-01)
      Engineered lactose particles were prepared by anti-solvent crystallisation technique using lactose solutions with different saturation degrees. In comparison to commercial lactose, engineered lactose particles exhibited less elongated and more irregular shape (large aggregates composed of smaller sub-units), rougher surface texture, higher specific surface area, and different anomer form. Engineered lactose powders demonstrated smaller bulk density, smaller tap density, and higher porosity than commercial lactose powder. Dry powder inhaler (DPI) formulations containing engineered lactose and salbutamol sulphate as a model drug demonstrated improved drug content homogeneity and higher amounts of drug delivered to lower airway regions. Higher fine particle fraction of drug was obtained in the case of lactose powders with higher porosity, higher specific surface area and higher fine particle content (<5 μm). The results indicated that the higher the saturation degree of lactose solution used during crystallisation the smaller the specific surface area, the higher the amorphous lactose content, and the higher the β-lactose content of engineered lactose particles. Also, lactose powders obtained from lactose solution with higher degree of saturation showed higher bulk and tap densities and smaller porosity. Engineered lactose powders crystallized from lower saturation degree (20% and 30% w/v) deposited higher amounts of drug on lower airway regions. In conclusion, this study demonstrated that it is possible to prepare engineered lactose particles with favourable properties (e.g. higher fine particle fraction and better drug content homogeneity) for DPI formulations by using lactose solutions with lower degree of saturation during crystallisation process.
    • Antisolvent precipitation of novel xylitol-additive crystals to engineer tablets with improved pharmaceutical performance.

      Kaialy, Waseem; Maniruzzaman, Mohammad; Shojaee, Saeed; Nokhodchi, Ali (Elsevier, 2014-12-30)
      The purpose of this work was to develop stable xylitol particles with modified physical properties, improved compactibility and enhanced pharmaceutical performance without altering polymorphic form of xylitol. Xylitol was crystallized using antisolvent crystallization technique in the presence of various hydrophilic polymer additives, i.e., polyethylene glycol (PEG), polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) at a range of concentrations. The crystallization process did not influence the stable polymorphic form or true density of xylitol. However, botryoidal-shaped crystallized xylitols demonstrated different particle morphologies and lower powder bulk and tap densities in comparison to subangular-shaped commercial xylitol. Xylitol crystallized without additive and xylitol crystallized in the presence of PVP or PVA demonstrated significant improvement in hardness of directly compressed tablets; however, such improvement was observed to lesser extent for xylitol crystallized in the presence of PEG. Crystallized xylitols produced enhanced dissolution profiles for indomethacin in comparison to original xylitol. The influence of additive concentration on tablet hardness was dependent on the type of additive, whereas an increased concentration of all additives provided an improvement in the dissolution behavior of indomethacin. Antisolvent crystallization using judiciously selected type and concentration of additive can be a potential approach to prepare xylitol powders with promising physicomechanical and pharmaceutical properties.
    • Aristolochic acids detected in some raw Chinese medicinal herbs and manufactured herbal products--a consequence of inappropriate nomenclature and imprecise labelling?

      Cheung, Thomas P.; Xue, Charlie; Leung, Kelvin Sze-Yin; Chan, Kelvin C.; Li, Chun G. (Taylor & Francis, 2006)
      BACKGROUND: Certain frequently used Chinese herbal medicines commonly used for weight control, may contain toxic Aristolochia species, which have been associated with severe nephropathy and urothelial cancer in humans and animals. The toxic entities in Aristolochia species are aristolochic acid-I (AA-I) and aristolochic acid-II (AA-II). There is a lack of systematic information about the aristolochic acid content of Aristolochia species and related genera, including those in Chinese materia medica that are used in the treatment of overweight individuals. OBJECTIVES: To determine the content of AA-I and AA-II of commonly used Chinese herbal medicines (raw herbs and manufactured products) including species of Aristolochia and related genera. METHODS: Twenty-one raw herbs and seven manufactured herbal products were purchased from herbal wholesalers and traditional Chinese medicinal herb retailers in Melbourne, Australia in September 2003, after the supply of known aristolochic acid-containing herbs and products had been banned in Australia. Six additional raw herbs were sourced from a herbal teaching museum. These were purchased in 2001, before the prohibition. The contents of aristolochic acids of each was determined by high pressure liquid chromatography (HPLC), and confirmed by liquid chromatography-mass spectrometry (LC-MS). RESULTS: Of the samples tested, four of the raw herbs purchased before the ban and two manufactured products purchased after the ban, were found to contain aristolochic acids (16-1002 ppm). CONCLUSIONS: Several Chinese raw herbs and some commercially available manufactured herbal products contain aristolochic acids. The confusion in Chinese nomenclature for related raw herbs, and imprecise labelling of manufactured products may contribute to the inadvertent use of toxic herbal species in Chinese medicine practice. Additional measures are needed to ensure the safety of consumers of Chinese herbal medicines.
    • Assay of free ferulic acid and total ferulic acid for quality assessment of Angelica sinensis.

      Lu, Guang-Hua; Chan, Kelvin C.; Leung, Kelvin Sze-Yin; Chan, Chi-Leung; Zhao, Zhong-Zhen; Jiang, Zhi-Hong (2005)
      Activity of Chinese Danggui (DG), the processed root of Angelica sinensis (Oliv.) Diels, is linked to the ferulic acid content but the stability of ferulic acid during extraction for medicinal use is not known. The stabilities of ferulic acid and coniferyl ferulate were evaluated in the extracts of DG using a variety of extraction solvents. These included various combinations and proportions of methanol, water, formic acid, 1 M aqueous hydrochloric acid and 2% sodium hydrogen carbonate (NaHCO3) in water. Coniferyl ferulate was found liable to hydrolyze into ferulic acid in neutral, strongly acidic and basic solvents, where heat and water could facilitate this hydrolysis. However, the hydrolysis was relatively resisted in weakly organic acid. Based on the stability evaluation, two new terms, namely: free ferulic acid and total ferulic acid, were suggested and defined. Free ferulic acid refers to the natural content of ferulic acid in herbs. Total ferulic acid means the sum of free ferulic acid plus the amount of related hydrolyzed components. Meanwhile, the high-performance liquid chromatographic (HPLC) method was developed to assay free ferulic acid and total ferulic acid in DG using methanol-formic acid (95:5) and methanol-2% NaHCO3 in water (95:5) as extraction solvents, respectively. Ten DG samples were investigated on their contents of free and total ferulic acid. The results indicated that the amount variety of free ferulic acid was larger than that of their counterparts, and the ratio of total ferulic acid to free ferulic acid was 4.07 +/- 2.73 (mean +/- SD, n = 10). The chemical assay of DG using total ferulic acid content would be a better choice to assess the herbal quality and was recommended.
    • Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft.

      Tin, Mandy; Cho, Chi-Hin; Chan, Kelvin C.; James, Anthony; Ko, Joshua (Oxford Journals, 2007)
      Astragalus memebranaceus is used as immunomodulating agent in treating immunodeficiency diseases and to alleviate the adverse effects of chemotherapeutic drugs. In recent years, it has been proposed that Astragalus may possess anti-tumorigenic potential in certain cancer cell types. In this study, the anti-carcinogenic effects of Astragalus saponin extract were investigated in HT-29 human colon cancer cells and tumor xenograft. Our findings have shown that Astragalus saponins (AST) inhibit cell proliferation through accumulation in S phase and G2/M arrest, with concomitant suppression of p21 expression and inhibition of cyclin-dependent kinase activity. Besides, AST promotes apoptosis in HT-29 cells through caspase 3 activation and poly(ADP-ribose) polymerase cleavage, which is indicated by DNA fragmentation and nuclear chromatin condensation. Nevertheless, we also demonstrate the anti-tumorigenic effects of AST in vivo, of which the reduction of tumor volume as well as pro-apoptotic and anti-proliferative effects in HT-29 nude mice xenograft are comparable with that produced by the conventional chemotherapeutic drug 5-fluorouracil (5-FU). In addition, the side effects (body weight drop and mortality) associated with the drug combo 5-FU and oxaliplatin are not induced by AST. These results indicate that AST could be an effective chemotherapeutic agent in colon cancer treatment, which might also be used as an adjuvant in combination with other orthodox chemotherapeutic drugs to reduce the side effects of the latter compounds.
    • Building a bridge for integrating Chinese medicine into conventional healthcare: observations drawn from the development of the Chinese quality of life instrument.

      Zhao, Li; Chan, Kelvin C. (World Scientific Publishing Company, 2005)
      This paper describes the methods and theories of patient-reported outcomes, in particular to the health-related quality of life recently applied in Chinese medicine research. It begins with an investigation of the reasons for a patient-reported outcomes measure for Chinese medicine and the development of a new health-related quality of life instrument based on Chinese culture and Chinese medicine. Discussions on the importance and application of patient-reported outcomes as well as the relationship between quality of life and Chinese medicine are at the focus of this paper. Through a description of the Chinese Quality of Life Instrument and its development, the present work demonstrates an evidence-based approach using patient-reported outcomes or health-related quality of life measures to evaluate treatment efficacy of Chinese medicine, and thereby build a bridge for the integration of Chinese medicine into mainstream health care.
    • Characterisation and in vitro antimicrobial potential of liposome encapsulated silver ions against Candida albicans.

      Kenward, M A; Hill, D J; Martin, C; Low, Wan Li (Taylor & Francis, 2016-01)
      Liposomes are biocompatible, biodegradable, controlled delivery systems with the ability to encapsulate both lipophilic and hydrophilic compounds, including metal ions. Liposome encapsulated Ag(+) (lipo-Ag(+)), prepared by reverse-phase evaporation, was used as a controlled delivery system against Candida albicans. Characterisation of the lipo-Ag(+) indicated that the multilamellar vesicles with diameters ranging between ≈ 0.5 and 5.0 μm showed potential as a controlled delivery system to consistently deliver Ag(+) to C. albicans. Results from inductively coupled plasma (ICP) analysis showed higher association of cell bound Ag(+) at 15 mins post exposure when compared to unencapsulated Ag(+). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) indicate detrimental effects of Ag(+) on C. albicans cell structure. These effects along with the ICP results also correlate with previously reported time kill experiment observations.
    • Cholesterol-bile salt vesicles as potential delivery vehicles for drug and vaccine delivery.

      Martin, C.; Thongborisute, J.; Takeuchi, H.; Yamamoto, H.; Kawashima, Y.; Alpar, H.O. (Elsevier Science Direct, 2005)
      The aim of this study was to further investigate the interactions between cholesterol (CH) and mixed bile salts (BS) (sodium cholate and sodium deoxycholate) and their suitability for drug and vaccine delivery. Insulin was used as a model protein to assess the ability of CH:BS vesicles to entrap a therapeutically relevant macromolecule. The association of protein (FITC-insulin) with the CH:BS structure was confirmed with fluorescence microscopy, and the overall morphology of the vesicles was examined with atomic force microscopy (AFM). Results demonstrate that the nature of the vesicles formed between CH and BS is dependent not only on the concentration of BS but also on the increasing CH concentration leading to CH crystal formation.
    • Comparative evaluation of drug release from aged prolonged polyethylene oxide tablet matrices: effect of excipient and drug type.

      Shojaee, Saeed; Kaialy, Waseem; Cumming, Kenneth Iain; Nokhodchi, Ali (Informa healthcare, 2014-11-20)
      Abstract Polyethylene oxide (PEO) undergoes structural adjustments caused by elevated temperatures, which results in loss of its stability within direct compression tablets. The aim of this study was to evaluate the influence of filler solubility on the drug delivery process of matrix tablets containing drugs with different water-solubility properties and stored at elevated temperature. The results demonstrated that in the case of propranolol HCl (highly water-soluble) tablet matrices, soluble lactose promoted drug release, whereas, a stable release of drug was observed with insoluble DCP. A drug release pattern similar to the propranolol HCl formulation containing DCP was obtained for hydrophilic matrix tablets containing either lactose or DCP for the less water-soluble drug, zonisamide. In the case of the partially water-soluble drug, theophylline, formulated with lower molecular weight PEO 750, drug release increased considerably in the presence of both fillers with increasing storage time, however a stable release rate (similar to fresh samples) was observed in the case of higher molecular weight PEO 303 tablet matrices containing theophylline with either lactose or DCP. The hydration properties (e.g. solubility) of the diluents had a considerable effect on drug release behavior from various model matrices; this effect was dependent on both molecular weight of PEO and solubility of drug.
    • Computational predictions of glass-forming ability and crystallization tendency of drug molecules.

      Alhalaweh, Amjad; Alzghoul, Ahmad; Kaialy, Waseem; Mahlin, Denny; Bergström, Christel A S (ACS Publications, 2014-09-02)
      Amorphization is an attractive formulation technique for drugs suffering from poor aqueous solubility as a result of their high lattice energy. Computational models that can predict the material properties associated with amorphization, such as glass-forming ability (GFA) and crystallization behavior in the dry state, would be a time-saving, cost-effective, and material-sparing approach compared to traditional experimental procedures. This article presents predictive models of these properties developed using support vector machine (SVM) algorithm. The GFA and crystallization tendency were investigated by melt-quenching 131 drug molecules in situ using differential scanning calorimetry. The SVM algorithm was used to develop computational models based on calculated molecular descriptors. The analyses confirmed the previously suggested cutoff molecular weight (MW) of 300 for glass-formers, and also clarified the extent to which MW can be used to predict the GFA of compounds with MW < 300. The topological equivalent of Grav3_3D, which is related to molecular size and shape, was a better descriptor than MW for GFA; it was able to accurately predict 86% of the data set regardless of MW. The potential for crystallization was predicted using molecular descriptors reflecting Hückel pi atomic charges and the number of hydrogen bond acceptors. The models developed could be used in the early drug development stage to indicate whether amorphization would be a suitable formulation strategy for improving the dissolution and/or apparent solubility of poorly soluble compounds.
    • Crystal engineering of ibuprofen using starch derivatives in crystallization medium to produce promising ibuprofen with improved pharmaceutical performance

      Nokhodchi, Ali; Homayouni, Alireza; Araya, Ruta; Kaialy, Waseem; Obeidat, Wasfy; Asare-Addo, Kofi (Royal Society of Chemistry, 2015)
      Ibuprofen exhibits poor flow, poor compaction and dissolution behaviour, and it is prone to capping after ejection from the die. Therefore, the aim of the present research was to engineer ibuprofen crystals in the presence of two disintegrants (starch and sodium starch glycolate) in order to improve its flow, compactibility and dissolution behaviour simultaneously. To this end ibuprofen and different concentrations of disintegrant (0.25 to 10% w/w in case of starch and 0.25 to 7% w/w in case of sodium starch glycolate) were dissolved in ethanol and water respectively. The ibuprofen solution was then added to the aqueous solutions containing the different concentrations of disintegrant. Ibuprofen precipitated within 10 min and the crystals were separated and dried for further studies. The obtained crystals were characterized in terms of flow, density, tablet hardness, dissolution behaviour and solid state. The results showed most of engineered ibuprofen to have better flow with a high compactibility. The results also showed that an increase in the concentration of starch in the crystallization medium resulted in a reduction in the hardness of ibuprofen tablets, but this was not the case for ibuprofen samples engineered in the presence of sodium starch glycolate. It is interesting to note that although engineered ibuprofen showed superior dissolution as compared to untreated ibuprofen, the highest concentration of starch (10%) or sodium starch glycolate (7%) slowed down the release remarkably due to an increase in the viscosity of the dissolution medium around drug particles. Solid state analysis (FT-IR, XRPD and DSC) ruled out the presence of different polymorphic forms and also any interaction between these disintegrants and ibuprofen. In conclusion, the engineering of ibuprofen in the presence of disintegrant showed how properties such as flow, compaction and dissolution behaviour can be simultaneously manipulated to suit a desired application.
    • Determination of free and total available ferulic acid in different types of Chinese angelica by high performance liquid chromatography

      Lu, Guang-Hua; Leung, Kelvin Sze-Yin; Chan, Kelvin C.; Cheng, SiQi; Zhang, Hao; Zhao, Zhong-Zhen (Taipei City, Taiwan: Bureau of Food and Drug Analysis (BFDA), 2007)
      Free and conjugated forms of ferulic acid (FA) are generally available in higher plant taxa such as Chinese Angelica (CA, the roots of Angelica sinensis (Oliv.) Diels). These various forms of FA were found readily inter-convertible and the extractable level of each depended on solvent properties and acidity. Extraction efficiency using various pH solutions namely, water, 70% methanol, methanol-formic acid (95:5) and methanol-2% NaHCO3 in water (95:5) was compared. Extractable FA were found varying in samples under neutral solvents extraction, whilst relatively consistent for slightly acidic and alkali solvents which were therefore chosen as the optimal media to extract and determine the reproducible levels of free and total available FA. An accurate and rapid high performance liquid chromatographic (HPLC) analysis was conducted using an Alltima C18 column (5 mum, 4.6 mm i.d. x 250 mm) with a guard column (C18, 5 mum, 4.6 mm i.d. x 7.5 mm) at 30degreesC, eluted with a mixture of 1.0% acetic acid and acetonitrile in a gradient program at a flow rate of 1.0 mL/min and detected at 320 nm. Altogether 20 different types of CA samples including whole root, root head, rootlets, whole root slice, Angelica processed by Chinese yellow wine, and charred Angelica were quantified for free and total available FA. Total available FA was found more abundant than free counterpart with an average ratio of 3.15 (n = 20) in the range of 1.29 to 8.23 for these CA samples. The extraction protocol was proven reliable to quantitatively convert all conjugated FA into its free forms and thereby accurately determined by HPLC method for quality assessment.
    • Determination of oleanolic acid in Caulis clematidis armandii by HPLC

      Qing, Lin-Sen; Zhang, Hao; Lu, Guang-Hua; Chan, Kelvin C.; Leung, Kelvin Sze-Yin; Chen Chu, Sze-Yin (ILIB, 2006)
      OBJECTIVE: To develop an HPLC method for the content determination of oleanolic acid in Caulis clematidis armandii after hydrolysis. METHODS: In the system of HPLC, a Alltima C_(18)(250 mm×4.6 mm,5 μm) column was used with a mixture of methanol-water-acetic acid-triethylamine(89∶11∶0.04∶0.02) as the mobile phase.The measuring wavelength was set at 207 nm.The flow rate was 1.0 ml·min~(-1) and the column temperature maintained at 45 ℃.RESULTS The oleanolic acid peak in chromatograms was completely separated from ...
    • Development of a high performance liquid chromatography-tandem mass method for determination of bis(7)-tacrine, a promising anti-Alzheimer's dimer, in rat blood.

      Yu, Hua; Ho, Jason; Kan, Kelvin K.; Cheng, Bobby; Li, Wen-Ming; Zhang, Li; Lin, Ge; Pang, Yuan-Ping; Gu, Zhe-Ming; Chan, Kelvin C.; Wang, Yi-Tao; Han, Yi-Fan (Amsterdam: Elsevier, 2007)
      An analytical method using on-line high performance liquid chromatography-tandem mass spectrometry with electrospray ionization was developed and applied for the quantification of bis(7)-tacrine (B7T) in rat blood. B7T and pimozide (internal standard, IS) were extracted in a single step from 100 microl of alkalized blood with ethyl acetate. Analytes were separated using an Extend C-18 column at 25 degrees C. The elution was achieved isocratically with a mobile phase composed of 0.05% aqueous formic acid and acetonitrile (60:40, v/v) at a flow rate of 0.35 ml/min. Quantification was achieved by monitoring the selected ions at m/z 247 for B7T and m/z 462-->m/z 328 for pimozide. Retention times were 1.45 and 2.23 min for B7T and IS, respectively. Calibration curves were linear in the range from 86.4 to 2160.0 ng/ml. The established method is rapid, selective and sensitive for the identification and quantification of B7T in biological samples. The assay is accurate (bias <10%) and reproducible (intra- and inter-day variation <10%), with detection and quantification limit of 3.6 and 42.3 ng/ml, respectively. Furthermore, it was successfully applied for the pharmacokinetic measurement of B7T in rat with a single intravenous administration at 0.3mg/kg.