Development of a new medium containing date syrup for production of bleomycin by Streptomyces mobaraensis ATCC 15003 using response surface methodology

A combined statistical approach of orthogonal design and polynomial regression were applied to optimize the composition and concentration of a liquid fermentation medium for the production of bleomycin (BLM) by Streptomyces mobaraensis. Optimal conditions for maximal productivity were determined based on eight parameters at three different levels. The sources of carbon and nitrogen concentration and their interactions with other precursors were found to be statistically significant factors. When date syrup was used as an additional carbon source, higher BLM amount was obtained in comparison to glucose. It was found that the optimum nitrogen source was achieved with the use of soyabean meal. The combined orthogonal design and response surface methodology predicted optimal conditions for production of BLM to be 138 mg dl-1. A confirmatory experiment of the optimal medium composition produced 142 mg dl-1 in the fifth day fermentation at 30°C. The complex medium containing 40 gml-1 date syrup as additional carbon source enhanced the production of BLM by 73%. The combined statistical approach enabled rapid identification and integration of key medium parameters for optimizing secondary metabolite production and could be very useful in pharma-ceutical screening programs.Keywords: Bleomycin, Streptomyces mobaraensis, orthogonal design, medium optimization, date syrupAfrican Journal of Biotechnology Vol. 9(33), pp. 5450-5459, 16 August, 201

Comparative bioavailability study of doxycycline hyclate (equivalent to 100 mg doxycycline) capsules (doxycin vs vibramycin) for bioequivalence evaluation in healthy adult volunteers.

This investigation was carried out to evaluate the bioavailability of a new capsule formulation of doxycycline (100 mg), doxycin, relative to the reference product, vibramycin (100 mg) capsules. The bioavailability was carried out in 24 healthy male volunteers who received a single dose (100 mg) of the test (A) and the reference (B) products after an overnight fast of at least 10 hours on 2 treatment days. The treatment periods were separated by a 2-week washout period. A randomized, balanced 2-way cross-over design was used. After dosing, serial blood samples were collected for a period of 48 hours. Plasma concentrations of doxycycline were analyzed by a sensitive and validated high-performance liquid chromatography assay. The pharmacokinetic parameters for doxycycline were determined using standard noncompartmental methods. The parameters AUC(0-t), AUC(0-infinity), Cmax, K(el), t(1/2) and Cmax/AUC(0-infinity) were analyzed statistically using log-transformed data. The time to maximum concentration (tmax) was analyzed using raw data. The parametric 90% confidence intervals of the mean values of the pharmacokinetic parameters: AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) were within the range 80-125% which is acceptable for bioequivalence (using log-transformed data). The calculated 90% confidence intervals based on the ANOVA analysis of the mean test/reference ratios of AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) were 95.98-109.56%, 92.21 to 107.66%, 93.90-112.56%, and 96.0 to 106.91% respectively. The test formulation was found bioequivalent to the reference formulation with regard to AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) by the Schuirmann's two 1-sided t-tests. Therefore, the 2 formulations were considered to be bioequivalen

Preparation and Characterization of Spironolactone-Loaded Gelucire Microparticles Using Spray-Drying Technique

The basic objectives of this study were to prepare and characterize solid dispersions of poorly soluble drug spironolactone (SP) using gelucire carriers by spray-drying technique. The properties of the microparticles produced were studied by differential scanning calorimetry (DSC), scanning electron microscopy, saturation solubility, encapsulation efficiency, and dissolution studies. The absence of SP peaks in DSC profiles of microparticles suggests the transformation of crystalline SP into an amorphous form. The in vitro dissolution test showed a significant increase in the dissolution rate of microparticles as compared with pure SP and physical mixtures (PMs) of drug with gelucire carriers. Therefore, the dissolution rate of poorly water-soluble drug SP can be significantly enhanced by the preparation of solid dispersion using spray-drying techniqueKing Saud Universit

High performance liquid chromatographic method for Determination of doxycycline in human plasma and its Application in pharmacokinetic studies

Corresponding Author: Dr. IBRAHIM A. ALSARRA College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Kingdom of Saudi Arabia Phone: +(966)-1-467-7504 Fax: +(966)-1-467-6295 Email: [email protected] accurate, sensitive and reproducible high performance liquid chromatographic (HPLC) method for the quantitation of doxycycline in plasma has been developed and validated. The drug and the internal standard were eluted from a μ-Bondapak C18 column (3.9 mm x 150 mm, I.D., 5 μm particle size) at room temperature with a mobile phase consisting of acetonitrile and water (28:72, % v/v). The flow rate was 0.8 ml/min. A UV detector set at 346 nm was used to monitor the effluent. Each analysis required no longer than 6 min. Quantitation was achieved by measurement of the peak area ratio of the drug to the internal standard. The limit of detection was 10.0 ng/ml and the limit of quantification of doxycycline in plasma was 0.10 μg/ml. The standard curve ranged from 0.1 to 2.5 μg/ml. The intraday coefficient of variation (C.V., %) ranged from 1.444 to 3.016%, and interday (C.V., %) from 1.572 to 2.705% at four different concentrations. The relative recoveries ranged from 98.43 to 105.13% and the absolute recoveries ranged from 54.08 to 62.56% at four different concentrations. Stability studies showed that doxycycline is stable for at least 4 weeks in plasma after freezing at - 20 °C. The method was applied for the determination of the pharmacokinetic parameters of doxycycline after oral administration of 100 mg capsules of two commercially available formulations to 6 human volunteers

Micromatricial metronidazole benzoate film as a local mucoadhesive delivery system for treatment of periodontal diseases

The main objective of this study was to develop a local, oral mucoadhesive metronidazole benzoate (MET) delivery system that can be applied and removed by the patient for the treatment of periodontal diseases. Mucoadhesive micromatricial chitosan/poly(ε-caprolactone) (CH/PCL) films and chitosan films were prepared. thermal behavior, morphology, and particle size measurements were used to evaluate the prepared films. The effect of different molar masses of CH and different ratios of medium Mwt molar mass chitosan (MCH):PCL on water absorption, in vitro bioadhesion, mechanical properties, and in vitro drug release was examined. In vivo performance of the selected formulation was also evaluated. Differential scanning calorimetry examination revealed that MET existed mainly in amorphous form. Under microscopic examination, PCL microparticles were homogeneously dispersed in the films. The use of different molar masses of CH and different ratios of (MCH):PCL affected the size of the entrapped particles. Addition of PCL significantly decreased percentage water uptake and bioadhesion force compared with pure CH film. With regard to mechanical properties, the 2-layered film containing 1∶0.625 MCH:PCL had the best tensile properties. At fixed CH:PCL ratio (1∶1.25), the slowest drug release was obtained from films containing high molar mass CH. On the other hand, the 2-layered film that consisted of 1∶0.625 MCH:PCL had the slowest MET release. In vivo evaluation of the selected film revealed that metronidazole concentration in saliva over 6 hours ranged from 5 to 15 μg/mL, which was within and higher than the reported range of minimum inhibitory concentration for metronidazole. A significant in vitro/in vivo correlation under the adopted experimental conditions was obtained