Formulation and Bioequivalence of Two Valsartan Tablets After a Single Oral Administration

The aim of this study is to assess the quality of Valzan® tablet (160 mg, valsartan immediate release test formulation) by comparing its pharmacokinetic parameters with Diovan® tablet (160 mg, valsartan reference formulation). Valzan® tablets were prepared according to a dry granulation method (roll compaction). To assess the bioequivalence of Valzan® tablets a randomized, two-way, crossover, bioequivalence study was performed in 24 healthy male volunteers. The selected volunteers were divided into two groups of 12 subjects. One group was treated with the reference formulation (Diovan®) and the other one with the generic Valzan®, with a cross-over after the drug washout period of 14 days. Blood samples were collected at fixed time intervals and valsartan concentrations were determined by a validated HPLC assay method. The pharmacokinetic parameters AUC0–48, AUC0–∞, Cmax, Tmax, Ke and T1/2 were determined for both the tablets and were compared statistically to evaluate the bioequivalence between the two brands of valsartan, using the statistical model recommended by the FDA. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals (CI) fell within the acceptable range for bioequivalence. Based on this statistical evaluation it was concluded that the test tablets (Valzan®) is well formulated, since it exhibits pharmacokinetic profile comparable to the reference brand Diovan®

Development of Film Coated Atrovastatin Calcium Tablet Using OPADRY-OY

The aim of this study was to develop and evaluate the stability of film coated Atorvastatin Calcium (AtC) tablets using Opadry-OY-B-28920. AtC uncoated tablets were developed and manufactured through the Wet Granulation process. Opadry-OY-B-28920 white aqueous coating dispersion was used as film coating material. The film coated tablets were completely disintegrated within 10 minutes in water media, it was also completely dissolved (more than 85% of the drug was released) within 30 minutes in pH 6.8 buffer solutions. The film coated tablets were studied under both long term and accelerated stability study and the results showed no significant variation in physical characteristics, color, hardness, no obvious defects or signs of peeling or chipping. These results reflect that the film coated system Opadry-OY-B-28920 can be successfully used in order to produce AtC film coated tablet that is protected from environmental conditions such as light and humidity.These findings suggest that aqueous film coating with Opadry-OY-B-28920 system is an easy and economical approach for preparing stable film coated AtC tablet of immediate release

Development of Film Coated Atrovastatin Calcium Tablet Using OPADRY-OY

The aim of this study was to develop and evaluate the stability of film coated Atorvastatin Calcium (AtC) tablets using Opadry-OY-B-28920. AtC uncoated tablets were developed and manufactured through the Wet Granulation process. Opadry-OY-B-28920 white aqueous coating dispersion was used as film coating material. The film coated tablets were completely disintegrated within 10 minutes in water media, it was also completely dissolved (more than 85% of the drug was released) within 30 minutes in pH 6.8 buffer solutions. The film coated tablets were studied under both long term and accelerated stability study and the results showed no significant variation in physical characteristics, color, hardness, no obvious defects or signs of peeling or chipping. These results reflect that the film coated system Opadry-OY-B-28920 can be successfully used in order to produce AtC film coated tablet that is protected from environmental conditions such as light and humidity.These findings suggest that aqueous film coating with Opadry-OY-B-28920 system is an easy and economical approach for preparing stable film coated AtC tablet of immediate release

Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method

Background: Montelukast (MT) is a leukotriene D4 antagonist. It is an effective and safe medicine for the prophylaxis and treatment of chronic asthma. It is also used to prevent acute exercise-induced bronchoconstriction and as a symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis. Objective: The aim of this study was to evaluate the bioequivalence (BE) of two drug products: generic MT 5 mg chewable tablets versus the branded drug Singulair® pediatric 5 mg chewable tablets among Mediterranean volunteers. Methods: An open-label, randomized two-period crossover BE design was conducted in 32 healthy male volunteers with a 9-day washout period between doses and under fasting conditions. The drug concentrations in plasma were quantified by using a newly developed and fully validated liquid chromatography tandem mass spectrometry method, and the pharmacokinetic parameters were calculated using a non-compartmental model. The ratio for generic/branded tablets using geometric least squares means was calculated for both the MT products. Results: The relationship between concentration and peak area ratio was found to be linear within the range 6.098–365.855 ng/mL. The correlation coefficient (R2) was always greater than 0.99 during the course of the validation. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between the generic and branded products. The point estimates (ratios of geometric means) were 101.2%, 101.6%, and 98.11% for area under the curve (AUC)0→last, AUC0→inf, and Cmax, respectively. The 90% confidence intervals were within the predefined limits of 80.00%–125.00% as specified by the US Food and Drug Administration and European Medicines Agency for BE studies. Conclusion: Broncast® pediatric chewable tablets (5 mg/tablet) are bioequivalent to Singulair® pediatric chewable tablets (5 mg/tablet), with a similar safety profile. This suggests that these two formulations can be considered interchangeable in clinical practice

SYNTHESIS AND FORMULATION OF IBUPROFEN PRO-DRUGS FOR ENHANCED TRANSDERMAL ABSORPTION

Objectives: The aim is to synthesize ibuprofen prodrugs that have more suitable physicochemical properties and formulate them into a liquid formulation for topical administration. The transdermal delivery (TDD) is one of the most attractive routes for drug administration as it eliminates the GIT absorption variable, improves patient compliance and also reduces drug plasma fluctuations. However, TDD only drugs with suitable physico-chemical properties can be absorbed. The oral administration of NSAIDs for a long time can cause gastric mucosal damage, which may result in ulceration and bleeding. Thus, the development of a TDD of NSAIDs is of great interest as it decreases GIT side effectsMethods: The synthesis of ibuprofen alkyl esters was carried out by esterification reactions with methanol, ethanol, propanol, butanol, pentanol and hexanol. The formulated samples were then subjected to stability studies according to ICH guidelines.Results: We have successfully synthesized and characterized various esters of ibuprofen. Moreover, ibuprofen butyl ester has been prepared as topical solutions. The formulated TDD was tested for stability according to ICH guidelines and the results showed no changes in the initial appearance during three months of study at room temperature & at 40 °C.Conclusion: The assay and pH were within the pharmacopeial limits during the period of the study. In conclusion, stable topical formulation of Ibuprofen esters was obtained.Â

Phytochemical, antimicrobial and antioxidant preliminary screening of a traditional Palestinian medicinal plant, Ononis pubescens L.

Antibiotic resistance has become a serious global concern, and the discovery of novel antimicrobial herbal constituents may provide valuable solutions to overcome this problem. It is important to identify new sources of natural antioxidants and antimicrobials. The present study describes for the first time the antioxidant, and antibacterial activities of various fractions of Ononis pubescens L., a traditional Palestinian medicinal plant. Methods: Antimicrobial activity was tested against selected strains from American Type Culture Collection (ATCC) and clinical isolates including Shigella sonnie, Staphylococcus aureus, Entrococuss feacium, Escherichia coli, Pseudomonas aeruginosa, Methicillin Resistant Staphylococcus aureus (MRSA), Candida albicans and Epidermatophyto flacosum using minimum inhibitory concentration (MIC) assay, while antioxidant activity was analyzed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. Results: A mixture of phytochemicals was found in all of the studied fractions of O. pubescens, which also showed remarkable potential with antioxidant and antimicrobial activities. Conclusion: The current study provides initial data that justify the use and importance of Ononis species in Palestinian folkloric medicine. Our results showed that Ononis pubescens n-hexane fraction has powerful antibacterial bioactivity against Staphylococcus aureus, as well as the acetone, n-hexane and methanol fractions which showed excellent potential against Epidermatophyto flacosum fungi, while the acetone fraction showed the highest antioxidant activity among other fractions. Further investigations are needed to identify and characterize these constituents.Financial support None. Acknowledgements The authors wish to thank An-Najah National University for its support to carry out this work and many thanks to the technicians Mohamad Arar and Linda Esa

Assessment of the antimicrobial and free radical scavenging activities of Moluccella spinosa, Helichrysum sanguineum, and Styrax officinalis folkloric medicinal plants from Palestine

The emergence of pathogenic microbes with increased resistance to established antibiotics provides a major incentive for the discovery of new antimicrobial agents. Herbals may provide valuable solutions for this global problem. In addition, the replacement of harmful synthetic antioxidants with natural ones may prevent various serious diseases. The present investigation describes for the first time the antioxidant and antimicrobial activities of the aqueous and organic extracts of Helichrysum sanguineum, Moluccella spinosa and Styrax officinalis plants aerial parts. The free radical scavenging activity was estimated using the 2,2-diphenyl-1-picrylhydrazyl method, while the antimicrobial activity was evaluated against selected microbial strains from American Type Culture Collection and clinical isolates such as Shigella sonnie, Staphylococcus aureus, Enterococcuss feacium, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, Epidermophyton floccosum and Methicillin Resistant Staphylococcus aureus (MRSA) using minimum inhibitory concentration assay. A mixture of phytochemical compounds was found in all of the studied plants extracts which also showed remarkable potentials of antioxidant and antimicrobial activities. The current study provides initial data that justify the use and importance of these plants in the Palestinian traditional medicine. In addition, it provides evidence that the aqueous and organic extracts of H. sanguineum, M. spinosa and S. officinalis exhibited interesting antioxidant activity comparing with Trolox. Furthermore, the organic extract of H. sanguineum strongly exhibited bacterial growth of S. aureus, E. faecium and MRSA which suggested to be used as antibiotic alternative or as sufficient natural food preservative.The authors acknowledge the assistance of the technicians Mohamad Arar and Linda Esa

Investigating the impacts of various solvents fractions of Bupleurum lancifolium on the antimicrobial and antioxidant potentials

In the last thirty years, interests in searching for plants with potential antimicrobial and antioxidant activities have been increased due to their probable health benefits. This study aimed to investigate the antimicrobial and antioxidant effects of various solvents fractions of Bupleurum lancifolium. Methods: The antioxidant activities of four fractions of Bupleurum lancifolium were assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay, while the antimicrobial activity was assessed by broth microdilution method. The antimicrobial activity of four plant fractions was examined against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Shigella sonnie and Enterococcus faecium American Type Culture Collection reference strains. Results: The fractionation extraction method succeeds in the assessment of the antibacterial and antioxidant activity of B. lancifolium plant. Hence the methanolic fraction has antioxidant potential with 33.03% of inhibition according to the Trolox antioxidant standard molecule, while n-hexane and methanol fractions showed powerful antibacterial activity against E. faecium and S. sonnie strains with Minimum Inhibitory Concentration (MIC)1.5625 mg/ml for both fractions. Conclusion: All plant fractions have potent antioxidant and antibacterial activities. Further investigations, i.e. isolation, identification, and clinical assessment, of the active compound(s) are needed for the possible formulation of new therapeutic alternatives.The authors acknowledge the assistance of the technicians Mohamad Arar and Linda Esa