Scientia Pharmaceutica

213 KiB

Open AccessArticle

Cytotoxic Compounds from Brucea mollis

by Mai Hung Thanh TUNG, Ho Viet ĐUC, Tran Thu HUONG, Nguyen Thanh DUONG, Do Thi PHUONG, Do Thi THAO, Bui Huu TAI, Young Ho KIM, Tran The BACH and Nguyen Manh CUONG

Sci. Pharm. 2013, 81(3), 819-832; https://doi.org/10.3797/scipharm.1206-02 - 29 Sep 2016

Cited by 8 | Viewed by 3064

Abstract

Ten compounds, including soulameanone (1), isobruceine B (2), 9-methoxy-canthin-6-one (3), bruceolline F (4), niloticine (5), octatriacontan-1-ol (6), bombiprenone (7), α-tocopherol (8), inosine (9), and apigenin [...] Read more.

Ten compounds, including soulameanone (1), isobruceine B (2), 9-methoxy-canthin-6-one (3), bruceolline F (4), niloticine (5), octatriacontan-1-ol (6), bombiprenone (7), α-tocopherol (8), inosine (9), and apigenin 7-O-β-D-glucopyranoside (10), were isolated from the leaves, stems, and roots of Brucea mollis Wall. ex Kurz. Their structures were determined using one- and two-dimensional NMR spectroscopy and mass spectrometry. All compounds were evaluated for their cytotoxic activity against KB (human carcinoma of the mouth), LU-1 (human lung adenocarcinoma), LNCaP (human prostate adeno-carcinoma), and HL-60 (human promyelocytic leukemia) cancer cell lines. Compound 2 showed significant cytotoxic activity against KB, LU-1, LNCaP, and HL-60 cancer cells with IC₅₀ values of 0.39, 0.40, 0.34, and 0.23 μg/mL, respectively. In addition, compounds 3 and 5 showed significant cytotoxic activity against KB, LU-1, LNCaP, and HL-60 cancer cells with IC₅₀ values around 1–4 μg/mL. Compounds 9-methoxycanthin-6-one (3) and niloticine (5) have been discovered for the first time from the Brucea genus. Full article

141 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Novel Alkyl-Imidazolyl Carbinols and their Esters: Potent Antimycotics

by Jürgen KRAUSS, Carina GRATZL, Verena STURM, Christoph MÜLLER, Verena STAUDACHER, Christoph Q. SCHMIDT and Franz BRACHER

Sci. Pharm. 2013, 81(3), 641-650; https://doi.org/10.3797/scipharm.1304-17 - 21 Aug 2013

Cited by 8 | Viewed by 1951

Abstract

A novel series of imidazol-5-yl carbinols and their 4-chlorobenzoyl esters has been synthesized by the Grignard reaction and subsequent esterification. These compounds were screened for their antimicrobial activities in an agar diffusion assay. The compounds with C₁₀ to C₁₂-alkyl side [...] Read more.

A novel series of imidazol-5-yl carbinols and their 4-chlorobenzoyl esters has been synthesized by the Grignard reaction and subsequent esterification. These compounds were screened for their antimicrobial activities in an agar diffusion assay. The compounds with C₁₀ to C₁₂-alkyl side chains displayed significant antimycotic activity. Full article

263 KiB

Open AccessArticle

Quantification of Sesquiterpene Lactones in Asteraceae Plant Extracts: Evaluation of their Allergenic Potential

by Helena SALAPOVIC, Johannes GEIER and Gottfried REZNICEK

Sci. Pharm. 2013, 81(3), 807-818; https://doi.org/10.3797/scipharm.1306-17 - 15 Aug 2013

Cited by 23 | Viewed by 2560

Abstract

Sesquiterpene lactones (SLs), mainly those with an activated exocyclic methylene group, are important allergens in Asteraceae (Compositae) plants. As a screening tool, the Compositae mix, consisting of five Asteraceae plant extracts with allergenic potential (feverfew, tansy, arnica, yarrow, and German chamomile) is part [...] Read more.

Sesquiterpene lactones (SLs), mainly those with an activated exocyclic methylene group, are important allergens in Asteraceae (Compositae) plants. As a screening tool, the Compositae mix, consisting of five Asteraceae plant extracts with allergenic potential (feverfew, tansy, arnica, yarrow, and German chamomile) is part of several national patch test baseline series. However, the SL content of the Compositae mix may vary due to the source material. Therefore, a simple spectrophotometric method for the quantitative measure-ment of SLs with the α-methylene-γ-butyrolactone moiety was developed, giving the percentage of allergenic compounds in plant extracts. The method has been validated and five Asteraceae extracts, namely feverfew (Tanacetum parthenium L.), tansy (Tanacetum vulgare L.), arnica (Arnica montana L.), yarrow (Achillea millefolium L.), and German chamomile (Chamomilla recutita L. Rauschert) that have been used in routine patch test screening were evaluated. A good correlation could be found between the results obtained using the proposed spectrophotometric method and the corresponding clinical results. Thus, the introduced method is a valuable tool for evaluating the allergenic potential and for the simple and efficient quality control of plant extracts with allergenic potential. Full article

313 KiB

Open AccessArticle

Compounds from Gum Ammoniacum with Acetylcholinesterase Inhibitory Activity

by Hamid-Reza ADHAMI, Johannes LUTZ, Hanspeter KÄHLIG, Martin ZEHL and Liselotte KRENN

Sci. Pharm. 2013, 81(3), 793-806; https://doi.org/10.3797/scipharm.1306-16 - 12 Aug 2013

Cited by 25 | Viewed by 2230

Abstract

The use of herbal medicinal preparations in dementia therapy has been studied based on experience from traditional medicine. A dichloromethane extract of gum ammoniacum, the gum-resin from Dorema ammoniacum D. Don had shown acetylcholinesterase (AChE) inhibitory activity in a previous study. The aim [...] Read more.

The use of herbal medicinal preparations in dementia therapy has been studied based on experience from traditional medicine. A dichloromethane extract of gum ammoniacum, the gum-resin from Dorema ammoniacum D. Don had shown acetylcholinesterase (AChE) inhibitory activity in a previous study. The aim of this study was the isolation and characterization of the active compounds from this resin. The extract was investigated by a respective colorimetric microplate assay and the active zones were identified via TLC bioautography and isolated using several chromatographic techniques. The structures of the active components were characterized by one- and two-dimensional ¹H and ¹³C NMR spectroscopy and mass spectrometry as (2'S,5'S)-2'-ethenyl-5'-(3-hy-droxy-6-methyl-4-oxohept-5-en-2-yl)-7-methoxy-2'-methyl-4H-spiro[chromene-3,1'-cyclopentane]-2,4-dione (1), which is an analogue of doremone A and a new natural compound, and as (2'S,5'R)-2'-ethenyl-5'-[(2R,4R)-4-hydroxy-6-methyl-3-oxohept-5-en-2-yl]-7-methoxy-2'-methyl-4H-spiro[chromene-3,1'-cyclo-pentane]-2,4-dione (2 = doremone A), (4E,8E)-1-(2,4-dihydroxyphenyl)-5,9,13-trimethyltetradeca-4,8,12-trien-1-one (3 = dshamirone), and 4,7-dihydroxy-3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl]-2H-chromen-2-one (4 = am-moresinol). Dshamirone turned out to be the most active compound with an IC50 value for AChE inhibitory activity of 23.5 μM, whereas the other substances showed weak activity. The concentrations of the analytes in the resin were determined by HPLC as 3.1%, 4.6%, 1.9%, and 9.9%, respectively. Full article

270 KiB

Open AccessArticle

Nitric Oxide is a Potential Diagnostic Marker for Hepatocellular Carcinoma

by Laila A. EISSA, Nada H. EISA, Mohamed A. EBRAHIM, Maha RAGAB and Amal M. EL-GAYAR

Sci. Pharm. 2013, 81(3), 763-776; https://doi.org/10.3797/scipharm.1307-09 - 8 Aug 2013

Cited by 12 | Viewed by 1530

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the seventh most common in women. This cancer varies widely in incidence throughout the world, with rising incidence in Egypt. HCC is considered the second most frequent cause of cancer incidence [...] Read more.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the seventh most common in women. This cancer varies widely in incidence throughout the world, with rising incidence in Egypt. HCC is considered the second most frequent cause of cancer incidence and mortality among men in Egypt. This study aimed to estimate the serum levels of nitric oxide (NO) and glutathione reductase in order to evaluate their role as oxidative status markers in HCC development and progression. For this purpose, serum levels of these parameters were assessed in 50 HCC patients, and 30 cirrhotic patients in addition to 15 healthy subjects as a control group. In the present study, glutathione reductase activity showed a significant increase in HCC as compared to the control group (P= 0.019). On the other hand, no significant difference was observed between the cirrhotic and HCC patients (P= 0.492). Serum NO was significantly higher in patients with HCC than in cirrhotic patients (P= 0.001) or the control group (P= 0.001), with a sensitivity of (74%) and specificity of (88.89%) at a cut-off level of 614.1 μmol/l. While AFP, alpha-fetoprotein, at a cutoff level of 200 ng/ml had a sensitivity of (52%), the specificity was (100%). Indeed, nitric oxide was high in 62.5% of AFP-negative HCC patients. In conclusion, glutathione reductase has no role in HCC diagnosis. However, nitric oxide is a potential diagnostic marker for HCC. The simultaneous determination of serum nitric oxide and AFP gave significant improvement in the detection of HCC patients compared to that of AFP alone. Full article

128 KiB

Open AccessShort Communication

How to Solve the Problems of Docking into a Symmetric Binding Site: The Example of the hERG Channel

by Andrea SCHIESARO, Lars RICHTER and Gerhard F. ECKER

Sci. Pharm. 2013, 81(3), 677-682; https://doi.org/10.3797/scipharm.1307-01 - 31 Jul 2013

Cited by 1 | Viewed by 1237

Abstract

Many proteins, such as the hERG K⁺ channel or the HIV-1 protease, have a high degree of rotational symmetry. If the binding site of a ligand is composed of symmetrical subunits, the analysis of the docking poses of ligands is quite challenging. [...] Read more.

Many proteins, such as the hERG K⁺ channel or the HIV-1 protease, have a high degree of rotational symmetry. If the binding site of a ligand is composed of symmetrical subunits, the analysis of the docking poses of ligands is quite challenging. In the case of hERG, the four-fold symmetry of the entire channel is fully reflected in the binding site, which allows up to four poses with different coordinates of the ligand, but an identical interaction pattern. In light of our docking studies into the hERG potassium channel, we developed an algorithm (ROTALI) to detect the poses that are duplicates due to the symmetry of the channel. This led to a reduction in the number of poses to be considered in the subsequent steps by up to 52%. Full article

215 KiB

Open AccessArticle

Preparation and First Preclinical Evaluation of [¹⁸F]FE@SNAP: A Potential PET Tracer for the Melanin-Concentrating Hormone Receptor-1 (MCHR1)

by Cécile PHILIPPE, Lukas NICS, Markus ZEILINGER, Eva SCHIRMER, Helmut SPREITZER, Georgios KARANIKAS, Rupert LANZENBERGER, Helmut VIERNSTEIN, Wolfgang WADSAK and Markus MITTERHAUSER

Sci. Pharm. 2013, 81(3), 625-640; https://doi.org/10.3797/scipharm.1306-02 - 1 Jul 2013

Cited by 13 | Viewed by 1903

Abstract

The melanin-concentrating hormone (MCH) system is a new target for the treatment of human disorders. Since the knowledge of the MCH system's involvement in a variety of pathologies (obesity, diabetes, and deregulation of metabolic feedback mechanism) is based on in vitro or preclinical [...] Read more.

The melanin-concentrating hormone (MCH) system is a new target for the treatment of human disorders. Since the knowledge of the MCH system's involvement in a variety of pathologies (obesity, diabetes, and deregulation of metabolic feedback mechanism) is based on in vitro or preclinical studies, a suitable positron emission tomography (PET) tracer needs to be developed. We herein present the preparation and first preclinical evaluation of [¹⁸F]FE@SNAP – a new PET tracer for MCH receptor-1 (MCHR1). The synthesis was performed using a microfluidic device. Preclinical evaluation included binding affinity, plasma stability, plasma free fraction, stability against the cytochrome P-450 (CYP450) system using liver microsomes, stability against carboxyl-esterase, and methods to assess the penetration of the blood-brain barrier (BBB) such as logD analysis and immobilized artificial membrane (IAM) chromatography. Levels at 374 ± 202 MBq [¹⁸F]FE@SNAP were obtained after purification. The obtained Kd value of [¹⁸F]FE@SNAP was 2.9 nM. [¹⁸F]FE@SNAP evinced high stability against carboxylesterase, CYP450 enzymes, and in human plasma. LogD (3.83) and IAM chromatography results (Pm=0.51) were in the same range as for known BBB-penetrating compounds. The synthesis of [¹⁸F]FE@SNAP was reliable and successful. Due to high binding affinity and stability, [¹⁸F]FE@SNAP is a promising tracer for MCHR1. Full article

354 KiB

Open AccessArticle

Evidence of Polymorphism on the Antitrypanosomal Naphthoquinone (4E)-2-(1H-Pyrazol-3-ylamino)- 4-(1H-pyrazol-3-ylimino)naphthalen-1(4H)-one

by Norma R. SPERANDEO and Sonia N. FAUDONE

Sci. Pharm. 2013, 81(3), 855-864; https://doi.org/10.3797/scipharm.1209-10 - 4 Jun 2013

Cited by 1 | Viewed by 1258

Abstract

The aim of this study was to characterize the solid state properties of (4E)-2-(1H-pyrazol-3-ylamino)-4-(1H-pyrazol-3-ylimino)naphthalen-1(4H)-one (BiPNQ), a compound with a significant inhibitory activity against Trypanosoma cruzi, the etiological agent of Chagas disease (American trypanosomiasis). [...] Read more.

The aim of this study was to characterize the solid state properties of (4E)-2-(1H-pyrazol-3-ylamino)-4-(1H-pyrazol-3-ylimino)naphthalen-1(4H)-one (BiPNQ), a compound with a significant inhibitory activity against Trypanosoma cruzi, the etiological agent of Chagas disease (American trypanosomiasis). Methods used included Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), Fourier Transform Infrared Spectroscopy (FTIR), Powder X-Ray Diffraction (PXRD), Hot Stage, and Confocal Microscopy. Two BiPNQ samples were obtained by crystallization from absolute methanol and 2-propanol-water that exhibited different thermal behaviours, PXRD patterns, and FTIR spectra, indicating the existence of an anhydrous form (BiPNQ-I) and a solvate (BIPNQ-s), which on heating desolvated leading to the anhydrous modification BiPNQ-I. It was determined that FTIR, DSC, and PXRD are useful techniques for the characterization and identification of the crystalline modifications of BiPNQ. Full article

704 KiB

Open AccessArticle

Pharmacological Analysis of the Rat Femoral Artery Response to Bradykinin

by Miroslav RADENKOVIĆ, Marko STOJANOVIĆ, Nebojša SKORUPAN and Milica PROSTRAN

Sci. Pharm. 2013, 81(3), 749-762; https://doi.org/10.3797/scipharm.1305-13 - 4 Jun 2013

Cited by 1 | Viewed by 1338

Abstract

Bradykinin (BK) plays an important role in different physiological processes including the general preservation and modulation of vascular systems. The present study was designed in order to examine the effect of BK on isolated rat femoral artery rings and to investigate the participation [...] Read more.

Bradykinin (BK) plays an important role in different physiological processes including the general preservation and modulation of vascular systems. The present study was designed in order to examine the effect of BK on isolated rat femoral artery rings and to investigate the participation of intact endothelium, cyclooxygenase products, Ca²⁺ channels, Na⁺/K⁺–ATPase, and B₂ kinin receptors in BK-induced action. Circular artery segments were placed in organ baths. The endothelium was mechanically removed from some arteries. Concentration–contraction curves for BK were obtained in the rings previously equilibrated at the basal tone. BK produced a concentration–dependent contraction, which was reduced by endothelial denudation. The BK–induced effect was almost completely inhibited by indomethacin (cyclooxygenase inhibitor) or OKY–046 (thromboxane A₂–synthase inhibitor). Nifedipine (Ca²⁺ channel blocker), ouabain (Na⁺/K⁺–ATPase inhibitor), or HOE–140 (selective B₂ kinin receptor antagonist) significantly reduced the BK–evoked effect. In conclusion, it can be proposed that BK produces concentration– and endothelium–dependent contractions of the isolated rat femoral artery, which is for the most part a consequence of B₂ kinin receptor activation. Cyclooxygenase contractile products, especially thromboxane A₂, play a significant role in this course of action. The transduction mechanism involved in the process of BK–induced femoral artery contraction include the activation of voltage–gated Ca²⁺ channels, and in a smaller extent Na⁺/K⁺–ATPase as well. Full article

663 KiB

Open AccessArticle

Poly-Ingredient Formulation Bresol^® Ameliorates Experimental Chronic Obstructive Pulmonary Disease (COPD) in Rats

by Mohamed RAFIQ, Gollapalle Lakshminarayanashastry VISWANATHA, Dattatray Anturlikar SURYAKANTH, Mohammed AZEEMUDDIN, Mahalingaiah JAGADEESH, Krishna DHANUSH and Pralhad Sadashiv PATKI

Sci. Pharm. 2013, 81(3), 833-842; https://doi.org/10.3797/scipharm.1212-06 - 9 May 2013

Cited by 4 | Viewed by 1699

Abstract

In the present study, the protective effect of Bresol^® – a polyherbal formulation – was evaluated in an experimental model of cigarette smoke (CS)-induced COPD in rats. Ten minutes daily exposure to CS for 7 weeks caused significant elevation of TNF-α (p<0.01) [...] Read more.

In the present study, the protective effect of Bresol^® – a polyherbal formulation – was evaluated in an experimental model of cigarette smoke (CS)-induced COPD in rats. Ten minutes daily exposure to CS for 7 weeks caused significant elevation of TNF-α (p<0.01) and total protein (p<0.01) in the bronchoalveolar lavage fluid (BALF) of positive untreated control animals, indicating ongoing inflammatory process in the lungs. Further, histopathological findings have confirmed the presence of pathological lesions in the trachea and lungs. Five weeks of post-treatment with Bresol^® (250 and 500 mg/kg,p.o.) showed significant and dose-dependent anti-inflammatory effects against CS-induced lung abnormalities by maintaining the TNF-α and total protein levels within the normal range. Additionally, Bresol^®-treated animals showed normal cyto-architecture of the trachea and lungs. In conclusion, Bresol^® showed dose-dependent protection against CS-induced lung and tracheal injury in rats, which further indicates, Bresol^® is a useful healing agent, may help to decelerate the progression of COPD, and reduce the exacerbations in patients. Full article

191 KiB

Open AccessArticle

Validation of a Stability-Indicating Hydrophilic Interaction Liquid Chromatographic Method for the Quantitative Determination of Vitamin K3 (Menadione Sodium Bisulfite) in Injectable Solution Formulation

by Mashhour M. GHANEM, Saleh A. ABU-LAFI and Hussein O. HALLAK

Sci. Pharm. 2013, 81(3), 733-748; https://doi.org/10.3797/scipharm.1303-05 - 9 May 2013

Viewed by 1884

Abstract

A simple, specific, accurate, and stability-indicating method was developed and validated for the quantitative determination of menadione sodium bisulfite in the injectable solution formulation. The method is based on zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) coupled with a photodiode array detector. The desired [...] Read more.

A simple, specific, accurate, and stability-indicating method was developed and validated for the quantitative determination of menadione sodium bisulfite in the injectable solution formulation. The method is based on zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) coupled with a photodiode array detector. The desired separation was achieved on the ZIC-HILIC column (250 mm × 4.6 mm, 5 μm) at 25°C temperature. The optimized mobile phase consisted of an isocratic solvent mixture of 200mM ammonium acetate (NH4AC) solution and acetonitrile (ACN) (20:80; v/v) pH-adjusted to 5.7 by glacial acetic acid. The mobile phase was fixed at 0.5 ml/min and the analytes were monitored at 261 nm using a photodiode array detector. The effects of the chromatographic conditions on the peak retention, peak USP tailing factor, and column efficiency were systematically optimized. Forced degradation experi-ments were carried out by exposing menadione sodium bisulfite standard and the injectable solution formulation to thermal, photolytic, oxidative, and acid-base hydrolytic stress conditions. The degradation products were well-resolved from the main peak and the excipients, thus proving that the method is a reliable, stability-indicating tool. The method was validated as per ICH and USP guidelines (USP34/NF29) and found to be adequate for the routine quantitative estimation of menadione sodium bisulfite in commercially available menadione sodium bisulfite injectable solution dosage forms. Full article

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Open AccessArticle

A Randomized, Crossover, Single-Dose Bioequivalence Study of Two Extended-Release Tablets of Donepezil 23 mg in Healthy Human Volunteers under Fasting and Fed States

by Chaitanya GADIKO, Sudhakar KOUNDINYA TIPPABHOTLA, Satyanarayana THOTA, Ramakrishna BATTULA, Sohel Md. KHAN and Venkateswarlu VOBALABOINA

Sci. Pharm. 2013, 81(3), 777-792; https://doi.org/10.3797/scipharm.1302-13 - 25 Apr 2013

Cited by 3 | Viewed by 1956

Abstract

To assess the bioequivalence of two extended-release tablets of donepezil 23 mg, open label, randomized, single-dose, two-sequence, two-period cross-over studies under fasting (n=74) and fed (n=94) conditions in healthy adult human volunteers were conducted. Subjects were randomized to either of the two treatment [...] Read more.

To assess the bioequivalence of two extended-release tablets of donepezil 23 mg, open label, randomized, single-dose, two-sequence, two-period cross-over studies under fasting (n=74) and fed (n=94) conditions in healthy adult human volunteers were conducted. Subjects were randomized to either of the two treatment arms (test or reference) separated by a washout period of 28 days. Blood samples were collected up to 72 h post-dose and plasma samples were analyzed for donepezil using a validated LC-MS/MS method. Pharmaco-kinetic parameters were derived using a non-compartmental approach. Bioequivalence was evaluated in 69 subjects in the fasting study, and 71 subjects in the fed study. In the fasting study, the 90% CI of Cmax and AUC0-72 were 82.50–90.10 and 92.38–98.60, respectively. Corresponding values in the fed study were 91.82–98.05 and 97.27–100.27. Based on the results, the test product (donepezil) met the US regulatory criteria of bioequivalence relative to the reference product (Aricept®) under both fasting and fed conditions. Full article

162 KiB

Open AccessArticle

Intranasal Delivery of Chitosan Nanoparticles for Migraine Therapy

by Neha GULATI, Upendra NAGAICH and Shubhini A. SARAF

Sci. Pharm. 2013, 81(3), 843-854; https://doi.org/10.3797/scipharm.1208-18 - 14 Apr 2013

Cited by 64 | Viewed by 1949

Abstract

Objective: The objective of the research was to formulate and evaluate sumatriptan succinate-loaded chitosan nanoparticles for migraine therapy in order to improve its therapeutic effect and reduce dosing frequency. Material and Methods: The Taguchi method design of experiments (L9 orthogonal array) was applied [...] Read more.

Objective: The objective of the research was to formulate and evaluate sumatriptan succinate-loaded chitosan nanoparticles for migraine therapy in order to improve its therapeutic effect and reduce dosing frequency. Material and Methods: The Taguchi method design of experiments (L9 orthogonal array) was applied to obtain the optimized formulation. The sumatriptan succinate-loaded chitosan nanoparticles (CNPs) were prepared by ionic gelation of chitosan with tripolyphosphate anions (TPP) and Tween 80 as surfactant. Results: The CNPs had a mean size of 306.8 ± 3.9 nm, a zeta potential of +28.79 mV, and entrapment efficiency of 75.4 ± 1.1%. The in vitro drug release of chitosan nanoparticles was evaluated in phosphate buffer saline pH 5.5 using goat nasal mucosa and found to be 76.7 ± 1.3% within 28 hours. Discussion: The release of the drug from the nanoparticles was anomalous, showing non-Fickian diffusion indicating that drug release is controlled by more than one process i.e. the superposition of both phenomena, a diffusion-controlled as well as a swelling-controlled release. This is clearly due to the characteristics of chitosan which easily dissolves at low pH, thus a nasal pH range of 5.5 ± 0.5 supports it very well. The mechanism of pH-sensitive swelling involves protonation of the amine groups of chitosan at low pH. This protonation leads to chain repulsion, diffusion of protons and counter ions together with water inside the gel, and the dissociation of secondary interactions. Conclusion: The results suggest that sumatriptan succinate-loaded chitosan nanoparticles are the most suitable mode of drug delivery for promising therapeutic action. Full article

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Open AccessArticle

Synthesis of 1,2,3-Triazole Derivatives and Evaluation of their Anticancer Activity

by Nazariy POKHODYLO, Olga SHYYKA and Vasyl MATIYCHUK

Sci. Pharm. 2013, 81(3), 663-676; https://doi.org/10.3797/scipharm.1302-04 - 14 Apr 2013

Cited by 85 | Viewed by 3238

Abstract

Anticancer screening of several 1,2,3-triazoles with heterocyclic fragments has been performed. The 1,2,3-triazole derivatives were synthesized from available starting materials according to convenient synthetic procedures. The antitumor activity of the synthesized compounds was tested in vitro by the National Cancer Institute in NCI60 [...] Read more.

Anticancer screening of several 1,2,3-triazoles with heterocyclic fragments has been performed. The 1,2,3-triazole derivatives were synthesized from available starting materials according to convenient synthetic procedures. The antitumor activity of the synthesized compounds was tested in vitro by the National Cancer Institute in NCI60 cell lines. It was observed that some compounds showed slight anticancer activity. One of them possessed a moderate activity against melanoma, colon, and breast cancer. Standard COMPARE analysis was performed at the GI₅₀level. Full article

1000 KiB

Open AccessArticle

Rivastigmine-Loaded L-Lactide-Depsipeptide Polymeric Nanoparticles: Decisive Formulation Variable Optimization

by Kunal PAGAR and Pradeep VAVIA

Sci. Pharm. 2013, 81(3), 865-888; https://doi.org/10.3797/scipharm.1211-20 - 28 Mar 2013

Cited by 46 | Viewed by 1685

Abstract

The main aim of the investigation was to explore a novel L-lactide-depsipeptide copolymer for the development of rivastigmine-loaded polymeric nanoparticles. L-lactide-depsipeptide synthesis was based on the ring opening polymerization reaction of L-lactide with the cyclodepsipeptide, cyclo(Glc-Leu), using tin 2-ethyl hexanoate as an initiator. [...] Read more.

The main aim of the investigation was to explore a novel L-lactide-depsipeptide copolymer for the development of rivastigmine-loaded polymeric nanoparticles. L-lactide-depsipeptide synthesis was based on the ring opening polymerization reaction of L-lactide with the cyclodepsipeptide, cyclo(Glc-Leu), using tin 2-ethyl hexanoate as an initiator. Rivastigmine-loaded nanoparticles were prepared by the single emulsion-solvent evaporation technique. The influence of various critical formulation variables like sonication time, amount of polymer, amount of drug, stabilizer concentration, drug-to-polymer ratio, and organic-to-aqueous phase ratio on particle size and entrapment efficiency was studied. The optimized formulation having a particle size of 142.2 ± 21.3 nm with an entrapment efficiency of 60.72 ± 3.72% was obtained. Increased rivastigmine entrapment within the polymer matrix was obtained with a relatively low organic-to-aqueous phase ratio and high drug-to-polymer ratio. A decrease in the average size of the nanoparticles was observed with a decrease in the amount of polymer added and an increase in the sonication time. Prolonged sonication time, however, decreased rivastigmine entrapment. From the different lyoprotectant tested, only trehalose was found to prevent nanoparticle aggregation upon application of the freeze-thaw cycle. Drug incorporation into the polymeric matrix was confirmed by the DSC and XRD study. The spherical nature of the nanoparticles was confirmed by the SEM study. The in vitro drug release study showed the sustained release of more than 90% of the drug up to 72 h. Thus, L-lactide-depsipeptide can be used as an efficient carrier for the nanoparticle preparation of rivastigmine. Full article

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Open AccessArticle

Validated Stability-Indicating HPLC-DAD Method for the Simultaneous Determination of Diclofenac Sodium and Diflunisal in Their Combined Dosage Form

by Rasha A. SHAALAN and Tarek S. BELAL

Sci. Pharm. 2013, 81(3), 713-732; https://doi.org/10.3797/scipharm.1301-24 - 17 Mar 2013

Cited by 27 | Viewed by 2974

Abstract

A simple, rapid, and highly selective HPLC-DAD method was developed for the simultaneous determination of diclofenac sodium (DIC) and diflunisal (DIF) in pure form and in their combined formulation. Effective chromatographic separation was achieved using a Zorbax SB-C8 (4.6×250 mm, 5 μm particle [...] Read more.

A simple, rapid, and highly selective HPLC-DAD method was developed for the simultaneous determination of diclofenac sodium (DIC) and diflunisal (DIF) in pure form and in their combined formulation. Effective chromatographic separation was achieved using a Zorbax SB-C8 (4.6×250 mm, 5 μm particle size) column with a mobile phase composed of 0.05 M phosphoric acid, acetonitrile, and methanol in the ratio of 40:48:12 (by volume). The mobile phase was pumped isocratically at a flow rate of 1 mL/min, and quantification of the analytes was based on measuring their peak areas at 228 nm. The retention times for diflunisal and diclofenac were about 7.9 and 9.5 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection, and quantification limits. Calibration curves were linear in the ranges of 5–100 μg/mL for both drugs with correlation coefficients >0.9998. The proposed method proved to be selective and stability-indicating by the resolution of the two analytes from four of their related substances and potential impurities as well as from forced-degradation (hydrolysis, oxidation, photolysis, and dry heat) products. The validated HPLC method was successfully applied to the analysis of DIC and DIF in their combined dosage form (suppositories). The proposed method made use of the diode array detector (DAD) as a tool for peak identity and purity confirmation. Full article

888 KiB

Open AccessArticle

Development and Validation of a Stability-Indicating RP-HPLC Method for the Determination of Process-Related Impurities and Degradation Products of Rabeprazole Sodium in Pharmaceutical Formulation

by Navneet KUMAR and Dhanaraj SANGEETHA

Sci. Pharm. 2013, 81(3), 697-712; https://doi.org/10.3797/scipharm.1301-25 - 17 Mar 2013

Cited by 2 | Viewed by 1824

Abstract

The objective of the current study was to develop and validate a reversed-phase high-performance liquid chromatographic method for the quantitative determination of process-related impurities and degradation products of rabeprazole sodium in pharmaceutical formulation. Chromatographic separation was achieved on the Waters Symmetry Shield RP18 [...] Read more.

The objective of the current study was to develop and validate a reversed-phase high-performance liquid chromatographic method for the quantitative determination of process-related impurities and degradation products of rabeprazole sodium in pharmaceutical formulation. Chromatographic separation was achieved on the Waters Symmetry Shield RP18 (250 mm x 4.6 mm) 5 μm column with a mobile phase containing a gradient mixture of solvent A (mixture of 0.025 M KH₂PO₄ buffer and 0.1% triethylamine in water, pH 6.4 and acetonitrile in the ratio of 90:10 v/v, respectively) and solvent B (mixture of acetonitrile and water in the ratio of 90:10 v/v, respectively). The mobile phase was delivered at a flow rate of 1.0 mL/min and with UV detection at 280 nm. Rabeprazole sodium was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal, and photolytic degradation. Rabeprazole sodium was found to degrade significantly under acid hydrolysis, base hydrolysis, oxidative, and thermal degradation conditions. The degradation products were well-resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. The mass balance was found to be in the range of 97.3–101.3% in all of the stressed conditions, thus proving the stability-indicating power of the method. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision, and robustness. Full article

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Open AccessArticle

Identification and Characterization of Process-Related Impurities of Trans-Resveratrol

by Balasubramanian SIVAKUMAR, Raman MURUGAN, Annamalai BASKARAN, Bhausaheb Pandharinath KHADANGALE, Saravanan MURUGAN and Udayampalayam Palanisamy SENTHILKUMAR

Sci. Pharm. 2013, 81(3), 683-696; https://doi.org/10.3797/scipharm.1301-17 - 17 Mar 2013

Cited by 11 | Viewed by 1771

Abstract

This article deals with the identification and characterization of process-related impurities of trans-resveratrol (3,5,4'-trihydroxystilbene), which exhibits several health benefits, including cancer prevention. During the synthesis of the bulk drug resveratrol, three new impurities were observed. The impurities were detected using the high-performance liquid [...] Read more.

This article deals with the identification and characterization of process-related impurities of trans-resveratrol (3,5,4'-trihydroxystilbene), which exhibits several health benefits, including cancer prevention. During the synthesis of the bulk drug resveratrol, three new impurities were observed. The impurities were detected using the high-performance liquid chromatographic (HPLC) method, whose area percentages ranged from 0.05 to 0.3%. A systematic study was carried out to characterize them. These impurities were isolated by preparative HPLC and characterized by spectral data, subjected to co-injection in HPLC, and were found to be matching with the impurities present in the sample. LC-MS was performed to identify the mass of these impurities. Based on their spectral data (IR, NMR, and Mass), these impurities were characterized as 2-benzyl-5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol [Impurity-B], 3-(benzyloxy)-5-[(E)-2-(4-hydroxyphenyl)ethenyl]phenol [Impurity-C], 5-{(E)-2-[4-(benzyloxy)phenyl]ethenyl}benzene-1,3-diol [Impurity-D). These compounds are not reported earlier as process-related impurities. Full article

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Open AccessArticle

Synthesis and Characterization of Potential Dimers of Gatifloxacin – an Antibacterial Drug

by Srinivas GARAGA, Ambati V. RAGHAVA REDDY, Koilpillai Joseph PRABAHAR, Raghu Babu KORUPOLU and Paul Douglas SANASI

Sci. Pharm. 2013, 81(3), 651-662; https://doi.org/10.3797/scipharm.1212-21 - 18 Feb 2013

Cited by 1 | Viewed by 2096

Abstract

Gatifloxacin is an antibacterial agent belonging to the fourth-generation fluoroquinolone family. Four piperazine-linked fluoroquinolone dimers of Gatifloxacin were observed during the laboratory process for Gatifloxacin and they were identified. The present work describes the origin, synthesis, characterization, and control of these dimers along [...] Read more.

Gatifloxacin is an antibacterial agent belonging to the fourth-generation fluoroquinolone family. Four piperazine-linked fluoroquinolone dimers of Gatifloxacin were observed during the laboratory process for Gatifloxacin and they were identified. The present work describes the origin, synthesis, characterization, and control of these dimers along with the synthesis of Despropylene Gatifloxacin (metabolite). Full article

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Sci. Pharm., Volume 81, Issue 3 (September 2013) – 19 articles , Pages 625-888

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