Scientia Pharmaceutica

200 KiB

Open AccessArticle

Cytotoxic and Antifungal Activities of Diverse α-Naphthylamine Derivatives

by Vladímir V. KOUZNETSOV, Susana A. ZACCHINO, Maximiliano SORTINO, Leonor Y. VARGAS MÉNDEZ and Mahabir P. GUPTA

Sci. Pharm. 2012, 80(4), 867-878; https://doi.org/10.3797/scipharm.1209-03 - 23 Oct 2012

Cited by 2 | Viewed by 1326

Abstract

Diverse α-naphthylamine derivatives were easily prepared from corresponding aldimines derived from commercially available α-naphthaldehyde and anilines or isomeric pyridinecarboxyaldehydes and α-naphthylamine. The secondary amines obtained were tested as possible antifungal and cytotoxic agents. The diverse N-aryl-N-[1-(1-naphthyl)but-3-enyl]amines obtained were [...] Read more.

Diverse α-naphthylamine derivatives were easily prepared from corresponding aldimines derived from commercially available α-naphthaldehyde and anilines or isomeric pyridinecarboxyaldehydes and α-naphthylamine. The secondary amines obtained were tested as possible antifungal and cytotoxic agents. The diverse N-aryl-N-[1-(1-naphthyl)but-3-enyl]amines obtained were active (IC₅₀< 10 μg/mL) against breast (MCF-7), non-small cell lung (H-460), and central nervous system (SF-268) human cancer cell lines, while N-(pyridinylmethyl)-naphthalen-1-amines resulted in activity against (MIC 25–32 μg/mL) some human opportunistic pathogenic fungi including yeasts, hialohyphomycetes, and dermatophytes. Full article

339 KiB

Open AccessArticle

Decreased Hippocampal 5-HT and DA Levels Following Sub-Chronic Exposure to Noise Stress: Impairment in both Spatial and Recognition Memory in Male Rats

by Saida HAIDER, Fizza NAQVI, Zehra BATOOL, Saiqa TABASSUM, Tahira PERVEEN, Sadia SALEEM and Darakhshan Jabeen HALEEM

Sci. Pharm. 2012, 80(4), 1001-1012; https://doi.org/10.3797/scipharm.1207-15 - 7 Oct 2012

Cited by 31 | Viewed by 1871

Abstract

Mankind is exposed to a number of stressors, and among them noise is one which can cause intense stress. High levels of background noise can severely impair one’s ability to concentrate. The present study was aimed to investigate the effect of sub-chronic noise [...] Read more.

Mankind is exposed to a number of stressors, and among them noise is one which can cause intense stress. High levels of background noise can severely impair one’s ability to concentrate. The present study was aimed to investigate the effect of sub-chronic noise stress on cognitive behavior and hippocampal monoamine levels in male rats. The study was performed on 12 male Wistar rats, divided into two groups; the control and noise-exposed. The rats in the test group were subjected to noise stress, 4h daily for 15 days. Cognitive testing was performed by the Elevated Plus Maze test (EPM) and Novel Object Recognition test (NOR). HPLC-EC was used to determine hippocampal monoamine levels and their metabolites. The data obtained revealed a significant decrease in hippocampal serotonin (5-hydroxytryptamine; 5-HT) and dopamine (DA) levels, whereas turnover ratios of 5-HT and DA were significantly increased compared to the controls. Rats exposed to noise exhibited a significant decrement in spatial memory. A significantly decreased recognition index of rats exposed to noise as compared to the control was also observed in the NOR test. Results of the present findings suggest the role of decreased hippocampal 5-HT and DA in the impairment of cognitive function following noise exposure. Full article

376 KiB

Open AccessArticle

Substituted 2-[(2-Oxo-2H-[1,2,4]triazino [2,3-c]quinazolin-6-yl)thio]acetamides with Thiazole and Thiadiazole Fragments: Synthesis, Physicochemical Properties, Cytotoxicity, and Anticancer Activity

by Sergey I. KOVALENKO, Inna S. NOSULENKO, Alexey Yu. VOSKOBOYNIK, Galina G. BEREST, Lyudmyla N. ANTYPENKO, Alexey N. ANTYPENKO and Andrey M. KATSEV

Sci. Pharm. 2012, 80(4), 837-866; https://doi.org/10.3797/scipharm.1208-07 - 4 Oct 2012

Cited by 14 | Viewed by 1538

Abstract

The series of novel N-R-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)thio]acetamides with thiazole and thiadiazole fragments in a molecule were obtained by alkylation of potassium salts 1.1–1.4 by N-hetaryl-2-chloro-acetamides and by aminolysis of activated acids 2.1–2.4 with N,N'-carbonyl-diimidazole (CDI). The structures of [...] Read more.

The series of novel N-R-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)thio]acetamides with thiazole and thiadiazole fragments in a molecule were obtained by alkylation of potassium salts 1.1–1.4 by N-hetaryl-2-chloro-acetamides and by aminolysis of activated acids 2.1–2.4 with N,N'-carbonyl-diimidazole (CDI). The structures of compounds were determined by IR, 1H NMR, MS, and EI-MS analysis. The results of cytotoxicity evaluated by the bio-luminescence inhibition of bacterium Photobacterium leiognathi, Sh1 showed that the compounds have considerable cytotoxicity. The synthesized compounds were tested for anticancer activity in NCI against 60 cell lines. Among the highly active compounds 3.1, 3.2, and 6.5, 2-[(3-methyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)thio]-N-(1,3-thiazol-2-yl)acetamide (3.1) was found to be the most active anticancer agent against the cell lines of colon cancer (GI₅₀ at 0.41–0.69 μМ), melanoma (GI₅₀ 0.48–13.50 μM), and ovarian cancer (GI₅₀ 0.25–5.01 μM). The structure-activity relationship (SAR-analysis) was discussed. Full article

285 KiB

Open AccessArticle

Development of a Stability-Indicating RP-HPLC Method for the Determination of Rupatadine and its Degradation Products in Solid Oral Dosage Form

by Harshal Kanubhai TRIVEDI and Mukesh C. PATEL

Sci. Pharm. 2012, 80(4), 889-902; https://doi.org/10.3797/scipharm.1208-10 - 1 Oct 2012

Cited by 6 | Viewed by 2068

Abstract

A simple, sensitive, and reproducible reversed-phase high-performance liquid chromatography (RP-HPLC) method, coupled with a photodiode array detector, was developed for the determination of rupatadine (RUPA) and its related substances in pharmaceutical dosage forms. Chromatographic separation was achieved on the Hypersil BDS (150 x [...] Read more.

A simple, sensitive, and reproducible reversed-phase high-performance liquid chromatography (RP-HPLC) method, coupled with a photodiode array detector, was developed for the determination of rupatadine (RUPA) and its related substances in pharmaceutical dosage forms. Chromatographic separation was achieved on the Hypersil BDS (150 x 4.6 mm, 5 μm) column with a mobile phase containing a gradient mixture of a buffer (acetate buffer pH-6.0) and solvent (methanol). The eluted compounds were monitored at 264 nm for the related substances and assay, the flow rate was 1.0 mL/min, and the column oven temperature was maintained at 50°C. The developed method separated RUPA from its four known and three unknown impurities within 15.0 min. Rupatadine was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal, and photolytic degradation. Rupatadine was found to degrade significantly under oxidative stress conditions, and degrade slightly under acid, base, hydrolytic, thermal, and photolytic stress conditions. All impurities were well-resolved from each other and from the main peak, showing the stability-indicating power of the method. The developed method was validated as per the International Conference on Harmonization (ICH) guidelines. The developed and validated RP-HPLC method is LC-MS compatible and can be explored for the identification of eluted unknown impurities of RUPA. Full article

187 KiB

Open AccessArticle

Synthesis of New N,N'-Bis(5-arylidene-4-oxo-4,5-dihydrothiazolin-2-yl)piperazine Derivatives Under Microwave Irradiation and Preliminary Biological Evaluation

by Wacothon Karime COULIBALY, Ludovic PAQUIN, Anoubilé BÉNIÉ, Yves-Alain BEKRO, Emilie DURIEUX, Laurent MEIJER, Rémy LE GUÉVEL, Anne CORLU and Jean-Pierre BAZUREAU

Sci. Pharm. 2012, 80(4), 825-836; https://doi.org/10.3797/scipharm.1206-04 - 16 Sep 2012

Cited by 14 | Viewed by 1686

Abstract

New N,N'-bis(5-arylidene-4-oxo-4,5-dihydrothiazoline-2-yl)diamine derivatives 5 were prepared in two steps from rhodanine and piperazine, or 1,4-bis(3-amino-propyl)piperazine, under microwave reaction conditions with retention of configuration. Some of these compounds were tested for in vitro antiproliferative activities and for their kinase inhibitory potencies towards six [...] Read more.

New N,N'-bis(5-arylidene-4-oxo-4,5-dihydrothiazoline-2-yl)diamine derivatives 5 were prepared in two steps from rhodanine and piperazine, or 1,4-bis(3-amino-propyl)piperazine, under microwave reaction conditions with retention of configuration. Some of these compounds were tested for in vitro antiproliferative activities and for their kinase inhibitory potencies towards six kinases (CDK5/p25, GSK3α/β, DYRK1A, DYRK2, CLK1, and CLK2). The compound 5d showed nanomolar activity towards DYRK1A kinase (IC₅₀ = 0.041 μM). Full article

186 KiB

Open AccessArticle

A Validated Stability-Indicating HPLC Method for Routine Analysis of an Injectable Lincomycin and Spectinomycin Formulation

by Murad N. ABUALHASAN, Nidal BATRAWI, Oliver B. SUTCLIFFE and Abdel Naser ZAID

Sci. Pharm. 2012, 80(4), 977-986; https://doi.org/10.3797/scipharm.1207-13 - 10 Sep 2012

Cited by 12 | Viewed by 2243

Abstract

Lincomycin and spectinomycin combination therapy is widely used in veterinary medicine for the treatment of gastrointestinal and respiratory infections caused by lincomycin- and spectinomycin-sensitive microorganisms. A simple, reverse phase HPLC method for the analysis of samples of an injectable lincomycin and spectinomycin preparation [...] Read more.

Lincomycin and spectinomycin combination therapy is widely used in veterinary medicine for the treatment of gastrointestinal and respiratory infections caused by lincomycin- and spectinomycin-sensitive microorganisms. A simple, reverse phase HPLC method for the analysis of samples of an injectable lincomycin and spectinomycin preparation containing a mixture of inactive excipients has been developed. The HPLC was carried out using the RP-C₁₈ (250 mm × 4.0 mm, 5 μm) column, with the gradient mobile phase consisting of an acetonitrile and phosphate buffer at pH 6; the flow rate of 1 mL/min and ultraviolet detection at 220 nm. This method was validated in accordance with both FDA and ICH guidelines and showed good linearity, accuracy, precision, selectivity, and system suitability results within the acceptance criteria. A stability-indicating study was also carried out and indicated that this method can also be used for purity and degradation evaluation of these formulations. Full article

169 KiB

Open AccessArticle

Novel Validated Stability-Indicating UPLC Method for the Estimation of Naproxen and its Impurities in Bulk Drugs and Pharmaceutical Dosage Form

by Papanaboina VENKATARAO, Morrisetty NAGENDRA KUMAR and Maram RAVI KUMAR

Sci. Pharm. 2012, 80(4), 965-976; https://doi.org/10.3797/scipharm.1207-12 - 9 Sep 2012

Cited by 9 | Viewed by 1829

Abstract

A novel, reversed-phase ultra-performance liquid chromatographic method was developed and validated for the determination of related substances in Naproxen (NAP) bulk drugs and dosage forms. The related substances included degradation and process-related impurities. The method was developed using the Waters Acquity BEH C18 [...] Read more.

A novel, reversed-phase ultra-performance liquid chromatographic method was developed and validated for the determination of related substances in Naproxen (NAP) bulk drugs and dosage forms. The related substances included degradation and process-related impurities. The method was developed using the Waters Acquity BEH C18 column using the gradient program with mobile phase A of a pH 7.0 phosphate buffer and methanol in the ratio of 90: 10 (v/v) and mobile phase B as methanol and acetonitrile in the ratio of 50:50 (v/v). Naproxen and its impurities were monitored at 260 nm. Naproxen was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal, humidity, and photolytic degradations. The degradation products were well-resolved from the main peak and its impurities, proving the stability-indicating power of the method. The performance of the method was validated according to the present ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, ruggedness, and robustness. Full article

650 KiB

Open AccessArticle

Transfersomes: A Novel Vesicular Carrier for Enhanced Transdermal Delivery of Sertraline: Development, Characterization, and Performance Evaluation

by Ankit GUPTA, Geeta AGGARWAL, Samita SINGLA and Ritika ARORA

Sci. Pharm. 2012, 80(4), 1061-1080; https://doi.org/10.3797/scipharm.1208-02 - 31 Aug 2012

Cited by 155 | Viewed by 4430

Abstract

The aim of the present study was to investigate transfersomes as a transdermal delivery system for the poorly soluble drug, sertraline, in order to overcome the troubles associated with its oral delivery. Different transfersomal formulations were prepared with non-ionic surfactant (span 80), soya [...] Read more.

The aim of the present study was to investigate transfersomes as a transdermal delivery system for the poorly soluble drug, sertraline, in order to overcome the troubles associated with its oral delivery. Different transfersomal formulations were prepared with non-ionic surfactant (span 80), soya lecithin, and carbopol 940 by the rotary evaporation sonication method. The prepared formulations were characterized for light microscopy, particle size analysis, drug entrapment, turbidity, drug content, rheological studies, in vitro release, ex vivo permeation, and stability studies. The optimized formulation was evaluated for in vivo studies using the modified forced swim model test. FTIR studies showed compatibility of the drug with excipients. The result revealed that sertraline in all of the formulations was successfully entrapped with uniform drug content. Transfersomal gel containing 1.6% of the drug and 20% of span 80 was concluded to be the optimized formulation (EL-SP4), as it showed maximum drug entrapment (90.4±0.15%) and cumulative percent drug release(73.8%). The ex vivo permeation profile of EL-SP4 was compared with the transfersomal suspension, control gel, and drug solution. The transfersomal gel showed a significantly higher (p<0.05) cumulative amount of drug permeation and flux along with lower lag time than the drug solution and drug gel. It also owed to better applicability due to the higher viscosity imparted by the gel rather than the transfersomal suspension, and no skin irritation was observed. The modified forced swim test in mice revealed that the transfersomal gel had better antidepressant activity as compared to the control gel. Thus, the study substantiated that the transfersomal gel can be used as a feasible alternative to the conventional formulations of sertraline with advanced permeation characteristics for transdermal application. Full article

395 KiB

Open AccessArticle

Formulation and Characterization of Benzoyl Peroxide Gellified Emulsions

by Naresh Kumar THAKUR, Pratibha BHARTI, Sheefali MAHANT and Rekha RAO

Sci. Pharm. 2012, 80(4), 1045-1060; https://doi.org/10.3797/scipharm.1206-09 - 31 Aug 2012

Cited by 22 | Viewed by 3809

Abstract

The present investigation was carried out with the objective of formulating a gellified emulsion of benzoyl peroxide, an anti-acne agent. The formulations were prepared using four different vegetable oils, viz. almond oil, jojoba oil, sesame oil, and wheat germ oil, owing to their [...] Read more.

The present investigation was carried out with the objective of formulating a gellified emulsion of benzoyl peroxide, an anti-acne agent. The formulations were prepared using four different vegetable oils, viz. almond oil, jojoba oil, sesame oil, and wheat germ oil, owing to their emollient properties. The idea was to overcome the skin irritation and dryness caused by benzoyl peroxide, making the formulation more tolerable. The gellified emulsions were characterized for their homogeneity, rheology, spreadability, drug content, and stability. In vitro permeation studies were performed to check the drug permeation through rat skin. The formulations were evaluated for their antimicrobial activity, as well as their acute skin irritation potential. The results were compared with those obtained for the marketed formulation. Later, the histopathological examination of the skin treated with various formulations was carried out. Formulation F3 was found to have caused a very mild dysplastic change to the epidermis. On the other hand, the marketed formulation led to the greatest dysplastic change. Hence, it was concluded that formulation F3, containing sesame oil (6%w/w), was the optimized formulation. It exhibited the maximum drug release and anti-microbial activity, in addition to the least skin irritation potential. Full article

224 KiB

Open AccessArticle

New Stability-Indicating RP-UFLC Method for Determination of Trospium Chloride in Tablet Dosage Form

by Sagar Suman PANDA, Bera V. V. RAVI KUMAR, Ganeswar MOHANTA, Rabisankar DASH and Pinkal Kumar PATEL

Sci. Pharm. 2012, 80(4), 955-964; https://doi.org/10.3797/scipharm.1207-07 - 31 Aug 2012

Cited by 16 | Viewed by 1595

Abstract

A simple, precise, and accurate isocratic RP-UFLC stability-indicating assay method has been developed to determine trospium chloride in tablet dosage form. Isocratic separation was achieved on an Enable-C18G (250 mm × 4.6 mm i.d., particle size 5 μm) column at room temperature, the [...] Read more.

A simple, precise, and accurate isocratic RP-UFLC stability-indicating assay method has been developed to determine trospium chloride in tablet dosage form. Isocratic separation was achieved on an Enable-C18G (250 mm × 4.6 mm i.d., particle size 5 μm) column at room temperature, the mobile phase consisted of acetonitrile:0.01M TBAHS (50:50, v/v) at a flow rate of 1.0 ml/min, the injection volume was 20 μl, and PDA detection was carried out at 215 nm. The drug was subjected to acid and alkali hydrolysis, oxidation, photolysis, and heat as stress conditions. The method was validated for specificity, linearity, precision, accuracy, robustness, and system suitability. The method was linear in the drug concentration range of 10–300 μg/ml with the correlation coefficient being 0.999. The RSD for repeatability and intermediate precision was well below 2%. The mean recoveries were between 100.52–101.68% for trospium chloride. Full article

394 KiB

Open AccessArticle

Development of a High-Performance Liquid Chromatographic Method for Determination of Letrozole in Wistar Rat Serum and its Application in Pharmacokinetic Studies

by Sasmita Kumari ACHARJYA, Subrat Kumar BHATTAMISRA, Bhanoji Rao E. MUDDANA, Ravikumar V. V. BERA, Pinakini PANDA, Bibhu Prasad PANDA and Gitanjali MISHRA

Sci. Pharm. 2012, 80(4), 941-954; https://doi.org/10.3797/scipharm.1206-06 - 31 Aug 2012

Cited by 23 | Viewed by 1823

Abstract

A fast, sensitive, and specific reversed-phase high-performance liquid chroma-tographic (RP–HPLC) method for the determination of letrozole in Wistar rat serum was developed. In this method, liquid–liquid extraction of letrozole was achieved using diethyl ether as the extracting solvent. The analysis was carried out [...] Read more.

A fast, sensitive, and specific reversed-phase high-performance liquid chroma-tographic (RP–HPLC) method for the determination of letrozole in Wistar rat serum was developed. In this method, liquid–liquid extraction of letrozole was achieved using diethyl ether as the extracting solvent. The analysis was carried out on a reversed-phase C18 (250 mm × 4.6 mm, 5 μm) column with an isocratic mobile phase of methanol–water (70:30,v/v), at a flow rate of 1.0 mL min^–1. Detection was carried out at 239 nm with a UV–visible spectrophoto-metric detector. The method was shown to be selective and linear over the concentration range of 0.15–100 μg mL^–1. The intra-day and inter-day precision studies showed good reproducibility with coefficients of variation less than 11% for the analyte. The relative errors of intra– and inter–day accuracy were within −11.52 to −2.26%. The limit of quantification was evaluated to be 0.15 μg mL^–1. The method was successfully applied for the pharmacokinetic study of letrozole after oral administration of 10 mg kg^–1 of letrozole in six healthy Wistar rats. Full article

285 KiB

Open AccessArticle

Ameliorative Effects of Taurine Against Methimazole-Induced Cytotoxicity in Isolated Rat Hepatocytes

by Reza HEIDARI, Hossein BABAEI and Mohammad Ali EGHBAL

Sci. Pharm. 2012, 80(4), 987-1000; https://doi.org/10.3797/scipharm.1205-16 - 6 Aug 2012

Cited by 56 | Viewed by 1992

Abstract

Methimazole is used as an antithyroid drug to control the symptoms of hyperthyroidism and maintain patients in a euthyroid state. Administration of this drug is associated with agranulocytosis and hepatotoxicity, which are the two most significant adverse effects. The present investigation was conducted [...] Read more.

Methimazole is used as an antithyroid drug to control the symptoms of hyperthyroidism and maintain patients in a euthyroid state. Administration of this drug is associated with agranulocytosis and hepatotoxicity, which are the two most significant adverse effects. The present investigation was conducted to study the protective role of taurine against cytotoxicity induced by methimazole and its proposed reactive intermediary metabolite, N-methylthiourea, in an in vitro model of isolated rat hepatocytes.
At different points in time, markers such as cell viability, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential, and hepatocyte glutathione content were evaluated.
Treating hepatocytes with methimazole resulted in cytotoxicity characterized by the reduction in cell viability, an increase in ROS formation and lipid peroxidation, mitochondrial membrane potential collapse, and a reduction in cellular glutathione content. Furthermore, a significant amount of oxidized glutathione (GSSG) was formed when rat hepatocytes were treated with methimazole. N-methylthiourea toxicity was accompanied by a reduction in cellular GSH content, but no significant changes in lipid peroxidation, ROS formation, GSSG production, or changes in mitochondrial membrane potential were detected. Administration of taurine (200 μM) effectively reduced the toxic effects of methimazole or its metabolite in isolated rat hepatocytes. Full article

211 KiB

Open AccessArticle

Simultaneous Determination of Atorvastatin and Aspirin in Human Plasma by LC–MS/MS: Its Pharmacokinetic Application

by Ramakrishna GAJULA, Nageswara Rao PILLI, Vasu Babu RAVI, Rambabu MADDELA, Jaswanth Kumar INAMADUGU, Srinivasa Rao POLAGANI and Sobha BUSA

Sci. Pharm. 2012, 80(4), 923-940; https://doi.org/10.3797/scipharm.1206-12 - 6 Aug 2012

Cited by 30 | Viewed by 2625

Abstract

A simple, rapid, and sensitive liquid chromatography tandem mass spectro-metric (LC–MS/MS) assay method has been developed and fully validated for the simultaneous quantification of atorvastatin and aspirin in human plasma using a polarity switch. Proguanil and furosemide were used as the internal standards [...] Read more.

A simple, rapid, and sensitive liquid chromatography tandem mass spectro-metric (LC–MS/MS) assay method has been developed and fully validated for the simultaneous quantification of atorvastatin and aspirin in human plasma using a polarity switch. Proguanil and furosemide were used as the internal standards for the quantification of atorvastatin and aspirin, respectively. The analytes were extracted from human plasma by the liquid–liquid extraction technique using methyl tert-butyl ether. The reconstituted samples were chromatographed on a Zorbax XDB Phenyl column by using a mixture of 0.2% acetic acid buffer, methanol, and acetonitrile (20:16:64, v/v) as the mobile phase at a flow rate of 0.8 mL/min. Prior to detection, atorvastatin and aspirin were ionized using an ESI source in the multiple reaction monitoring (MRM) mode. The ions were monitored at the positive m/z 559.2→440.0 transition for atorvastatin and the negative m/z 179.0→136.6 transition for aspirin. The calibration curve obtained was linear (r² ≥ 0.99) over the concentration range of 0.20–151 ng/mL for atorvastatin and 15.0–3000 ng/mL for aspirin. The method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 3.0 min for each sample made it possible to analyze more than 300 human plasma samples per day. The proposed method was found to be applicable to clinical studies. Full article

356 KiB

Open AccessArticle

Stress Degradation Behavior of Abacavir Sulfate and Development of a Suitable Stability-Indicating UHPLC Method for the Determination of Abacavir, its Related Substances, and Degradation Products

by Pallavi VUKKUM, Girish R. DESHPANDE, J. Moses BABU, R. MURALIKRISHNA and Pavani JAGU

Sci. Pharm. 2012, 80(4), 903-922; https://doi.org/10.3797/scipharm.1206-11 - 27 Jul 2012

Cited by 10 | Viewed by 1908

Abstract

A novel, stability-indicating UHPLC method was developed for the quantitative determination of Abacavir sulfate, its related substances, and forced degra-dation impurities in bulk drugs. The chromatographic separation was achieved on a Waters Acquity BEH C₈, 50 mm × 2.1 mm, 1.7 [...] Read more.

A novel, stability-indicating UHPLC method was developed for the quantitative determination of Abacavir sulfate, its related substances, and forced degra-dation impurities in bulk drugs. The chromatographic separation was achieved on a Waters Acquity BEH C₈, 50 mm × 2.1 mm, 1.7 μm particle size column with a mobile phase containing a gradient mixture of solution A (0.10 % v/v o-phosphoric acid in water) and solution B (0.10% v/v o-phosphoric acid in methanol). The flow rate was set at 0.40 mL/min and the run time was 6.0 min. The drug substance was subjected to the stress studies of hydrolysis, oxidation, photolysis, and thermal degradation. Abacavir sulfate was found to degrade significantly under acidic hydrolysis and oxidative stress conditions. The formed degradation products were reported and were well-resolved from Abacavir and its related substances. The mass balance was found to be satisfactory in all of the stress conditions, thus proving the stability-indicating capability of the method. The developed UHPLC method was validated to be in agreement with ICH requirements and found to be rapid, accurate, precise, linear, specific, and suitable for the quantitative determination of related substances and degradants in the bulk drug samples of Abacavir sulfate. Full article

754 KiB

Open AccessArticle

Systematic Development of Self-Emulsifying Drug Delivery Systems of Atorvastatin with Improved Bioavailability Potential

by Fariba KHAN, Md. Saiful ISLAM, Monzurul Amin RONI and Reza-Ul JALIL

Sci. Pharm. 2012, 80(4), 1027-1044; https://doi.org/10.3797/scipharm.1201-06 - 22 Jul 2012

Cited by 31 | Viewed by 2104

Abstract

The aim of this study was to prepare and characterize a self-emulsifying drug delivery system (SEDDS) with a high drug load of poorly water-soluble atorvastatin for the enhancement of dissolution and oral bioavailability. Solubility of atorvastatin in oil, surfactant, and cosurfactant was determined. [...] Read more.

The aim of this study was to prepare and characterize a self-emulsifying drug delivery system (SEDDS) with a high drug load of poorly water-soluble atorvastatin for the enhancement of dissolution and oral bioavailability. Solubility of atorvastatin in oil, surfactant, and cosurfactant was determined. Pseudo-ternary phase diagrams were constructed by the aqueous titration method, and formulations were developed based on the optimum excipient combinations. A high drug load (10% w/w) was achieved with a combination of oleic acid, Tween 80, and polyethylene glycol 400, ensuring the maximum dissolution property (in the case of SES6). Effects of lipids and surfactants on physical properties of SEDDS such as in vitro emulsification efficiency in terms of self-emulsification time, emulsion droplet size, and percent transmittance were measured. Multiple regression analysis revealed that a higher amount of surfactants significantly increased dissolution of ATV while decreasing emulsion droplet size and emulsification time. About a four-fold increase in dissolution was achieved by SEDDS compared to pure ATV powder. Overall, this study suggests that dissolution and oral bioavailability of ATV could be improved by SEDDS technology. Full article

254 KiB

Open AccessArticle

Valeriana officinalis Dry Plant Extract for Direct Compression: Preparation and Characterization

by Loreana GALLO, María Veronica RAMÍREZ-RIGO, Juliana PIÑA, Santiago PALMA, Daniel ALLEMANDI and Verónica BUCALÁ

Sci. Pharm. 2012, 80(4), 1013-1026; https://doi.org/10.3797/scipharm.1206-05 - 12 Jul 2012

Cited by 18 | Viewed by 2151

Abstract

Valeriana officinalis L. (Valerianaceae) is one of the most widely used plants for the treatment of anxiety and insomnia. Usually dry plant extracts, including V. officinalis, are hygroscopic materials with poor physico-mechanical properties that can be directly compressed. A V. officinalis dry [...] Read more.

Valeriana officinalis L. (Valerianaceae) is one of the most widely used plants for the treatment of anxiety and insomnia. Usually dry plant extracts, including V. officinalis, are hygroscopic materials with poor physico-mechanical properties that can be directly compressed. A V. officinalis dry extract with moderate hygroscocity is suitable for direct compression, and was obtained by using a simple and economical technique. The V. officinalis fluid extract was oven-dried with colloidal silicon dioxide as a drying adjuvant. The addition of colloidal silicon dioxide resulted in a dry plant extract with good physico-mechanical properties for direct compression and lower hygroscopicity than the dry extract without the carrier. The dry plant extract glass transition temperature was considerably above room temperature (about 72 °C). The colloidal silicon dioxide also produced an antiplasticizing effect, improving the powder’s physical stability. The pharmaceutical performance of the prepared V. officinalis dry extract was studied through the design of tablets. The manufactured tablets showed good compactability, friability, hardness, and disintegration time. Those containing a disintegrant (Avicel PH 101) exhibited the best pharmaceutical performance, having the lowest disintegration time of around 40 seconds. Full article

165 KiB

Open AccessArticle

A Validated Stability-Indicating Liquid Chromatographic Method for Determination of Degradation Impurities and Diastereomers in Voriconazole Tablets

by Kabeer A. SHAIKH and Ashish T. PATIL

Sci. Pharm. 2012, 80(4), 879-888; https://doi.org/10.3797/scipharm.1204-24 - 18 Jun 2012

Cited by 13 | Viewed by 1636

Abstract

A reversed-phase gradient liquid chromatographic method has been developed for the quantitative determination of Voriconazole, along with its degradation and diastereomeric impurities in tablet dosage form. Chromatographic separation has been achieved on an Inertsil ODS 3V, 150 x 4.6 mm, 5 μm column. [...] Read more.

A reversed-phase gradient liquid chromatographic method has been developed for the quantitative determination of Voriconazole, along with its degradation and diastereomeric impurities in tablet dosage form. Chromatographic separation has been achieved on an Inertsil ODS 3V, 150 x 4.6 mm, 5 μm column. The mobile phase consisting of solvent A 0.05 molar (M) potassium dihydrogen phosphate (pH 2.5 buffer) and solvent B (mixture of acetonitrile and methanol in the ratio 90:10 (v/v)), was delivered at a flow rate of 1.2 mL min⁻¹ with the detection wavelength at 256 nm. Resolution of Voriconazole and all five potential impurities was achieved at greater than 2.0 for all pairs of compounds. The drug was subjected to stress conditions such as oxidative, acid and base hydrolysis, and thermal and photolytic degradation. Voriconazole was found to degrade significantly under base hydrolysis stress conditions compared to acid hydrolysis stress conditions. The degradation products were well-resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. The stressed samples were assayed against a reference standard and the mass balance was found to be close to 99.0%. 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 AccessReview

Biological Activities of 2-Mercaptobenzothiazole Derivatives: A Review

by Mohammed Afzal AZAM and Bhojraj SURESH

Sci. Pharm. 2012, 80(4), 789-824; https://doi.org/10.3797/scipharm.1204-27 - 18 Jun 2012

Cited by 101 | Viewed by 3451

Abstract

2-Mercaptobenzothiazoles are an important class of bioactive and industrially important organic compounds. These compounds are reported for their antimicrobial and antifungal activities, and are subsequently highlighted as a potent mechanism-based inhibitor of several enzymes like acyl coenzyme A cholesterol acyltransferase, monoamine oxidase, heat [...] Read more.

2-Mercaptobenzothiazoles are an important class of bioactive and industrially important organic compounds. These compounds are reported for their antimicrobial and antifungal activities, and are subsequently highlighted as a potent mechanism-based inhibitor of several enzymes like acyl coenzyme A cholesterol acyltransferase, monoamine oxidase, heat shock protein 90, cathepsin D, and c-Jun N-terminal kinases. These derivatives are also known to possess antitubercular, anti-inflammatory, antitumor, amoebic, antiparkinsonian, anthelmintic, antihypertensive, antihyperlipidemic, antiulcer, chemoprotective, and selective CCR3 receptor antagonist activity. This present review article focuses on the pharmacological profile of 2-mercaptobenzothiazoles with their potentialactivities. Full article

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Sci. Pharm., Volume 80, Issue 4 (December 2012) – 18 articles , Pages 789-1080

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