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Scientia Pharmaceutica is published by MDPI from Volume 84 Issue 3 (2016). Articles in this Issue were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence. Articles are hosted by MDPI on mdpi.com as a courtesy and upon agreement with Austrian Pharmaceutical Society (Österreichische Pharmazeutische Gesellschaft, ÖPhG).

Table of Contents

Sci. Pharm., Volume 83, Issue 3 (September 2015) , Pages 413-548

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Open AccessArticle
The Role of Polydimethylsiloxane in the Molecular Structure of Silica Xerogels Intended for Drug Carriers
Sci. Pharm. 2015, 83(3), 519-533; https://doi.org/10.3797/scipharm.1409-08
Received: 10 September 2014 / Accepted: 1 July 2015 / Published: 1 July 2015
Viewed by 574 | PDF Full-text (460 KB)
Abstract
The aim of this study was to prepare and examine polymer/oxide xerogels with metronidazole (MT) as delivery systems for the local application of a drug to a bone. The nanoporous SiO2-CaO and PDMS-modified SiO2-CaO xerogel materials with different amounts [...] Read more.
The aim of this study was to prepare and examine polymer/oxide xerogels with metronidazole (MT) as delivery systems for the local application of a drug to a bone. The nanoporous SiO2-CaO and PDMS-modified SiO2-CaO xerogel materials with different amounts of the polymer, polydimethylsiloxane (PDMS), were prepared by the sol-gel method. Characterization assays comprised the analysis of the composite materials by using Fourier transform infrared spectroscopy (FTIR), determining the specific surface area of solids (BET), using X-ray powder diffraction (XRD) and scanning electron microscope (SEM) techniques, and further monitoring in the ultraviolet and visible light regions (UV-Vis) of the in vitro release of the drug (metronidazole) over time. According to these results, the bioactive character and chemical stability of PDMS-modified silica xerogels have been proven. The release of MT from xerogels was strongly correlated with the composition of the matrix. In comparison with the pure oxide matrix, PDMS-modified matrices accelerated the release of the drug through its bigger pores, and additionally, on account of weaker interactions with the drug. The obtained results for the xerogel composites suggest that the metronidazole-loaded xerogels could be promising candidates for formulations in local delivery systems particularly to bone. Full article
Open AccessArticle
Dosage Form Data Used for Estimating Pediatric Antibiotic Use
Sci. Pharm. 2015, 83(3), 511-518; https://doi.org/10.3797/scipharm.1411-05
Received: 11 November 2014 / Accepted: 1 July 2015 / Published: 1 July 2015
Viewed by 572 | PDF Full-text (1009 KB)
Abstract
We aimed to report a simple estimation method to enable quantification of pediatric antibiotic exposure in large aggregated datasets. Secondly, we aimed to quantify and benchmark Hungarian pediatric antibiotic use. First we intended to examine whether a correlation existed between dosage form data [...] Read more.
We aimed to report a simple estimation method to enable quantification of pediatric antibiotic exposure in large aggregated datasets. Secondly, we aimed to quantify and benchmark Hungarian pediatric antibiotic use. First we intended to examine whether a correlation existed between dosage form data and the patient’s age. Therefore, issued prescriptions were analyzed in pharmacies. As a correlation was found between the share of liquid oral antibacterial products and the rate of pediatric antibiotic prescriptions (R=0.884; p<0.001), we extrapolated this finding to a large aggregated dataset and estimated that 34.6% of prescriptions were issued for pediatric cases (95% confidence interval: 19.7–60.0). Taking into account the demography of the population, children were exposed to antibiotics three times more often than adults with a corresponding annual prescription rate of 2.6. We demonstrated that simple drug-related data can be linked to a patient-related measure as we found strong associations between dosage form data and patients’ age. Based on this association, massive pediatric antibiotic exposure was found. Due to the general availability of dosage form data and the ease of the estimation method, the reported concept can be used to quantify pediatric antibiotic use in large aggregated datasets or when age stratification is absent. Full article
Open AccessArticle
Activation of HIV-1 with Nanoparticle-Packaged Small-Molecule Protein Phosphatase-1-Targeting Compound
Sci. Pharm. 2015, 83(3), 535-548; https://doi.org/10.3797/scipharm.1502-01
Received: 4 February 2015 / Accepted: 22 June 2015 / Published: 22 June 2015
Cited by 3 | Viewed by 695 | PDF Full-text (578 KB)
Abstract
Complete eradication of HIV-1 infection is impeded by the existence of latent HIV-1 reservoirs in which the integrated HIV-1 provirus is transcriptionally inactive. Activation of HIV-1 transcription requires the viral Tat protein and host cell factors, including protein phosphatase-1 (PP1). We previously developed [...] Read more.
Complete eradication of HIV-1 infection is impeded by the existence of latent HIV-1 reservoirs in which the integrated HIV-1 provirus is transcriptionally inactive. Activation of HIV-1 transcription requires the viral Tat protein and host cell factors, including protein phosphatase-1 (PP1). We previously developed a library of small compounds that targeted PP1 and identified a compound, SMAPP1, which induced HIV-1 transcription. However, this compound has a limited bioavailability in vivo and may not be able to reach HIV-1-infected cells and induce HIV-1 transcription in patients. We packaged SMAPP1 in polymeric polyethylene glycol polymethyl methacrylate nanoparticles and analyzed its release and the effect on HIV-1 transcription in a cell culture. SMAPP1 was efficiently packaged in the nanoparticles and released during a 120-hr period. Treatment of the HIV-1-infected cells with the SMAPP1-loaded nanoparticles induced HIV-1 transcription. Thus, nanoparticles loaded with HIV-1-targeting compounds might be useful for future anti-HIV-1 therapeutics. Full article
Open AccessArticle
Improved Automated Radiosynthesis of [11C]PBR28
Sci. Pharm. 2015, 83(3), 413-427; https://doi.org/10.3797/scipharm.1505-06
Received: 7 May 2015 / Accepted: 19 June 2015 / Published: 19 June 2015
Viewed by 540 | PDF Full-text (193 KB)
Abstract
Microglial activation is commonly identified by elevated levels of the 18 kDa translocator protein (TSPO) in response to several inflammatory processes. [11C]PBR28 is one of the most promising PET tracers to image TSPO in both human and non-human primates. In this [...] Read more.
Microglial activation is commonly identified by elevated levels of the 18 kDa translocator protein (TSPO) in response to several inflammatory processes. [11C]PBR28 is one of the most promising PET tracers to image TSPO in both human and non-human primates. In this study, we optimized the radiolabeling procedure of [11C]PBR28 for higher radiochemical yield, radiochemical purity, and specific activity, which can be easily translated to any automated module for clinical trials. Time-activity curves (TACs) derived from the dynamic PET imaging of male rhesus monkey brains demonstrated that [11C]PBR28 had suitable kinetics with radiotracer accumulation observed in the caudate, putamen, cerebellum, and frontal cortex region. Full article
Open AccessArticle
Synthesis and In Vitro Biological Evaluation of 1,3,4-Oxadiazol-2(3H)-one and Tetrahydropyridazine-3,6-dione Derivatives of Fatty Acids
Sci. Pharm. 2015, 83(3), 429-443; https://doi.org/10.3797/scipharm.1503-10
Received: 22 March 2015 / Accepted: 9 June 2015 / Published: 9 June 2015
Cited by 2 | Viewed by 557 | PDF Full-text (1025 KB)
Abstract
Herein we report saturated and unsaturated fatty acid derivatives of 1,3,4-oxadiazol-2(3H)-one and tetrahydropyridazine-3,6-dione as new potential anticancer agents. All the synthesised compounds were characterised by IR, 1H-NMR, 13C-NMR, and mass spectral data. The relative sensitivity of three cancer cell [...] Read more.
Herein we report saturated and unsaturated fatty acid derivatives of 1,3,4-oxadiazol-2(3H)-one and tetrahydropyridazine-3,6-dione as new potential anticancer agents. All the synthesised compounds were characterised by IR, 1H-NMR, 13C-NMR, and mass spectral data. The relative sensitivity of three cancer cell lines varied depending on the nature of the compound. Among the most effective anticancer compounds studied, 3b and 6b displayed remarkable anticancer activity against the MDA-MB-231 and KCL-22 lines, respectively. On the other hand, compound 3c was found to be most sensitive to nearly all the tested cell lines, MDA-MB-231, KCL-22, and HeLa. Full article
Open AccessArticle
Metabolite Profiling of Justicia gendarussa Burm. f. Leaves Using UPLC-UHR-QTOF-MS
Sci. Pharm. 2015, 83(3), 489-500; https://doi.org/10.3797/scipharm.1411-08
Received: 16 November 2014 / Accepted: 14 April 2015 / Published: 14 April 2015
Cited by 2 | Viewed by 620 | PDF Full-text (403 KB)
Abstract
An ultra-performance liquid chromatography ultra-high-resolution quadrupole-time-of-flight-mass spectrometry (UPLC-UHR-QTOF-MS) metabolite profiling of Justicia gendarussa Burm. f. leaves was performed. PCA and HCA analyses were applied to observe the clustering patterns and inter-sample relationships. It seemed that the concentrations of Ca, P, and Cu in [...] Read more.
An ultra-performance liquid chromatography ultra-high-resolution quadrupole-time-of-flight-mass spectrometry (UPLC-UHR-QTOF-MS) metabolite profiling of Justicia gendarussa Burm. f. leaves was performed. PCA and HCA analyses were applied to observe the clustering patterns and inter-sample relationships. It seemed that the concentrations of Ca, P, and Cu in the soil could affect the metabolite profiles of Justicia gendarussa. Six significant metabolites were proposed. Full article
Open AccessArticle
A Competent and Commercially Viable Process for the Synthesis of the Anti-Hypertensive Drug Olmesartan Medoxomil
Sci. Pharm. 2015, 83(3), 465-478; https://doi.org/10.3797/scipharm.1502-04
Received: 15 February 2015 / Accepted: 31 March 2015 / Published: 31 March 2015
Cited by 3 | Viewed by 613 | PDF Full-text (157 KB)
Abstract
Drug product purity and potency are of most significance in the regulatory market as we notice many recalled batches worldwide, particularly in the US and Japan. Olmesartan Medoxomil is an anti-hypertensive drug. The present invention relates to a process for the preparation of [...] Read more.
Drug product purity and potency are of most significance in the regulatory market as we notice many recalled batches worldwide, particularly in the US and Japan. Olmesartan Medoxomil is an anti-hypertensive drug. The present invention relates to a process for the preparation of Olmesartan Medoxomil with 99.9% purity in an overall 62% yield. The synthesis includes three isolations and one purification with easy plant operations. This process describes the formation and control of each individual impurity in all stages. This process for Olmesartan Medoxomil and its intermediates is competent for industrial production in very short reaction time intervals with an appreciable yield and high purity. Full article
Open AccessArticle
Cost-Effective Isolation of a Process Impurity of Pregabalin
Sci. Pharm. 2015, 83(3), 453-463; https://doi.org/10.3797/scipharm.1501-16
Received: 30 January 2015 / Accepted: 25 March 2015 / Published: 25 March 2015
Viewed by 740 | PDF Full-text (255 KB)
Abstract
Cost-effective isolation methods were developed on preparative HPLC, flash LC, and simulated moving bed (SMB) to prepare the process impurity, 3-(aminomethyl)-5-methylhex-4-enoic acid (4-ene impurity), of pregabalin. By a thorough experimental study on the different isolation techniques available, it was concluded that SMB was [...] Read more.
Cost-effective isolation methods were developed on preparative HPLC, flash LC, and simulated moving bed (SMB) to prepare the process impurity, 3-(aminomethyl)-5-methylhex-4-enoic acid (4-ene impurity), of pregabalin. By a thorough experimental study on the different isolation techniques available, it was concluded that SMB was the most cost-effective. Hence, it was a continuous chromatography that utilized the advantage of SMB so that a high quantity of the impurity was generated in a short period of time. SMB was equipped with eight reversed-phased columns and was used to separate the process impurity of pregabalin. The effects of flow rate in zone 2 (Q2) and 3 (Q3), as well as switching time, on the operating performance parameters like purity, productivity, and desorbent consumption were studied. Operating conditions leading to more than 90% purity in the raffinate outlet stream were identified, together with those achieving optimal performance. All of these developed methods are novel, cost-effective, and can be applied to the isolation of other process- and stability-related impurities of pregabalin. Full article
Open AccessArticle
Polysaccharide-Rich Fraction of Noni Fruit (Morinda citrifolia L.) as Doxorubicin Co-Chemotherapy: Evaluation of Catalase, Macrophages, and TCD8+ Lymphocytes
Sci. Pharm. 2015, 83(3), 479-488; https://doi.org/10.3797/scipharm.1410-01
Received: 1 October 2014 / Accepted: 12 March 2015 / Published: 12 March 2015
Viewed by 686 | PDF Full-text (120 KB)
Abstract
Noni fruit (Morinda citrifolia L.) has been acknowledged for its cytotoxic and immunostimulatory activity. Our previous results on the immunomodulatory effect of a noni juice polysaccharide-rich fraction encouraged this research to evaluate the potency of the polysaccharide-rich fraction as co-chemotherapy with doxorubicin (DOX) [...] Read more.
Noni fruit (Morinda citrifolia L.) has been acknowledged for its cytotoxic and immunostimulatory activity. Our previous results on the immunomodulatory effect of a noni juice polysaccharide-rich fraction encouraged this research to evaluate the potency of the polysaccharide-rich fraction as co-chemotherapy with doxorubicin (DOX) administration. Macrophage activity (MA) was evaluated with the latex bead method. The phagocytic index (PI) was measured as the number of latex beads ingested by 100 macrophages, while the phagocytosis ratio (PR) was indicated by the percentage of macrophages that ingested three or more latex beads. The CEC was evaluated by using a commercial assay kit, while CD8+ T lymphocyte proliferation was evaluated using a flowcytometry method following in vivo administration. Thirty male Wistar rats were divided into five groups (n = 6 each). The control group received DOX via i.p. at a concentration of 4.67 mg/kg BW on days 1 and 4; four treatment groups received PF p.o. at a concentration of 25; 50; 100; 200 mg/kg BW daily, respectively, and additionally DOX i.p. 4.67 mg/kg BW (days 1 and 4) for 7 days. The phagocytic activity was not affected significantly by PF administration compared to the Dox control, but PF administration at a dose of 25 and 50 mg/kg BW has been proven to increase TCD8+ cell proliferation in combination with DOX. The catalase concentration, on the other hand, significantly decreased following PF administration at a dose of 100 mg/kg BW. The results suggest that the polysaccharide-rich fraction of noni juice might induce immuno-modulatory effects via TCD8+ activation, have antioxidant activity, and thus might be a potential candidate to be used as an adjuvant to DOX chemo-therapy. Full article
Open AccessArticle
Synthesis of Isomeric and Potent Impurities of the Triazole-Based Antifungal Drug Voriconazole
Sci. Pharm. 2015, 83(3), 445-452; https://doi.org/10.3797/scipharm.1501-13
Received: 25 January 2015 / Accepted: 6 March 2015 / Published: 6 March 2015
Cited by 1 | Viewed by 666 | PDF Full-text (253 KB)
Abstract
We describe the synthesis of two positional isomers and a desfluoro impurity of Voriconazole starting with Friedel–Crafts acylation of mono- and difluoro-benzene. These isomers are the crucial components in determining the quality of Voriconazole during its manufacturing from the key raw material, 1-(2,4-difluorophenyl)-2-(1 [...] Read more.
We describe the synthesis of two positional isomers and a desfluoro impurity of Voriconazole starting with Friedel–Crafts acylation of mono- and difluoro-benzene. These isomers are the crucial components in determining the quality of Voriconazole during its manufacturing from the key raw material, 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-one. All the prepared impurities were characterized by IR, 1H-NMR, 13C-NMR, and mass spectral data. Full article
Open AccessArticle
Improved Pharmacokinetics of Aceclofenac Immediate Release Tablets Incorporating its Inclusion Complex with Hydroxypropyl-β-Cyclodextrin
Sci. Pharm. 2015, 83(3), 501-510; https://doi.org/10.3797/scipharm.1409-07
Received: 10 September 2014 / Accepted: 2 February 2015 / Published: 2 February 2015
Cited by 1 | Viewed by 622 | PDF Full-text (225 KB)
Abstract
The present investigation reports the various pharmacokinetic parameters of immediate release aceclofenac tablets incorporating its inclusion complex with hydroxypropyl-β-cyclodextrin. The tablets were prepared using aceclofenac: hydroxypropyl-β-cyclodextrin in a 1:1 molar ratio by the direct compression method (TKN). The results were compared with those [...] Read more.
The present investigation reports the various pharmacokinetic parameters of immediate release aceclofenac tablets incorporating its inclusion complex with hydroxypropyl-β-cyclodextrin. The tablets were prepared using aceclofenac: hydroxypropyl-β-cyclodextrin in a 1:1 molar ratio by the direct compression method (TKN). The results were compared with those of the marketed brand (MKT) and pure drug (TAC). The P-values indicated that mean plasma concentrations were significantly different among all three formulations administered (P<0.05, P<0.01). TKN showed significantly higher plasma levels when compared to the pure drug (P<0.01). The Cmax and AUC(0-∞) of TKN were significantly higher (P<0.05) compared to the pure drug and marketed formulation. Furthermore, the first-order overall elimination rate constant (Kel) of TKN was also significantly higher (P<0.05) compared to the pure drug and its marketed formulation. These results suggested that tablets prepared by incorporating the AC-HPβCD inclusion complex (TKN) would provide a more rapid onset of pharmacological effects in comparison to the marketed formulation and pure drug. Full article
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