Aims/introductionDue to the heterogeneous nature of type 2 diabetes mellitus and its complex effects on hemodynamics, there is a need to identify new candidate markers which are involved in the development of type 2 diabetes mellitus (DM) and can serve as potential targets. As the global diabetes prevalence in 2019 was estimated as 9.3% (463 million people), rising to 10.2% (578 million) by 2030 and 10.9% (700 million) by 2045, the need to limit this rapid prevalence is of concern. The study aims to identify the possible biomarkers of type 2 diabetes mellitus with the help of the system biology approach using R programming.Materials and methodsSeveral target proteins that were found to be associated with the source genes were further curated for their role in type 2 diabetes mellitus. The differential expression analysis provided 50 differentially expressed genes by pairwise comparison between the biologically comparable groups out of which eight differentially expressed genes were short-listed. These DEGs were as follows: MCL1, PTX3, CYP3A4, PTGS1, SSTR2, SERPINA3, TDO2, and GALNT7.ResultsThe cluster analysis showed clear differences between the control and treated groups. The functional relationship of the signature genes showed a protein–protein interaction network with the target protein. Moreover, several transcriptional factors such as DBX2, HOXB7, POU3F4, MSX2, EBF1, and E4F1 showed association with these identified differentially expressed genes.ConclusionsThe study highlighted the important markers for diabetes mellitus that have shown interaction with other proteins having a role in the progression of diabetes mellitus that can serve as new targets in the management of DM.
Epirubicin, commonly used as anticancer drug for various types of tumors like breast, liver, lung, stomach, ovaries, and bladder for its improved antitumor efficacy and safety. A rapid, sensitive, and reliable bioanalytical method was developed and validated for epirubicin using conventional reverse phase HPLC with UV detection. The developed method was successfully applied to investigate the pharmacokinetics of epirubicin after intravenous administration of a reference epirubicin and its designed nano-formulations to rats. C18 column was used in an isocratic mode for analyte elution at a flow rate of 1.0 mL/min with UV detection of 234 nm. The mobile phase was composed of acetonitrile 22% (channel A) and 0.025% tri fluoro-acetic acid in water (channel B). Ondansetron was added as an internal standard, and the plasma samples were analyzed after protein precipitation. A concentration range of 0.016–1.024 μg/mL was selected for the construction of calibration curves, with LLOQ of 0.016 μg/mL. Results showed that the value of AUC, half-life, and mean residence time of designed nano-formulation were bounce to 10, 9, and 11 times higher, when compared to the reference epirubicin after intravenous dose of 10 mg/kg of epirubicin to rats, respectively. The designed epirubicin nano-formulations achieved clinically significant pharmacokinetic values in rats. Current method will help epirubicin future research using clinical samples and drug bioequivalence studies on various novel formulations for drug safety purposes.
Most of the newly invented active pharmaceutical ingredients (APIs) are poor water soluble and dissolution rate is the limiting step in bioavailability from compressed solid dosage forms. Objective of the study was to elucidate the effect of hydrophilic carriers on dissolution rate of poor water soluble drug and utilization of co-grinded Clarithromycin in preparation of tablets by direct compression. Intrinsic dissolution rate of Clarithromycin was determined according to United States Pharmacopeia (USP) using rotating disk method. Hydrophilic carrier (micro crystalline cellulose) was applied in varying ratios (1:1, 1:2 and 1:4; drug to carrier ratio by weight) for enhancement of dissolution rate of Clarithromycin by co-grinding technique. Co-grinded Clarithromycin was prepared by compressing lubricated physical mixture (blend of Clarithromycin and micro crystalline cellulose) to slugs, followed by granulation. Tablets containing co-grinded Clarithromycin were prepared by direct compression technique and evaluated for various official and unofficial parameters at pre compression and post compression level. The prepared tablets were compared with marketed tablets in terms of physical parameters, mechanical strength, disintegration behavior and in-vitro drug release. Dissolution profiles of both types of the tablets were compared on the basis of maximum drug release, dissimilarity factor (f 1), similarity factor (f 2) and dissolution efficiency. Clarithromycin is a class-II drug, with poor water solubility. Its intrinsic dissolution rate is very low (0.678mg/cm 2 .min). In comparison to intrinsic dissolution rate, significant increase in dissolution rate of Clarithromycin was observed by co-grinding with hydrophilic carriers (267.11%). Dissolution rate of Clarithromycin enhanced with concentration of hydrophilic carrier and maximum increase was observed at 1:2 (drug to carrier ratio by weight). By further increasing ratio of the carrier resulted in decrease in dissolution rate due to cushioning effect. Tablets containing cogrinded Clarithromycin, showed better dissolution profile compared with marketed tablets. In comparison with marketed tablets, maximum drug release in 60min, Q60 (99.73±0.39), Q30 (75.81±0.19%), Q15 (31.17±0.26%), and dissolution efficiency (93.73%) were higher for tablets containing co-grinded Clarithromycin. Dissolution rate of poor water soluble drug (Clarithromycin) can be enhanced by co-grinding with hydrophilic carrier (micro crystalline cellulose). Co-grinding is an environment friendly technique that can be applied for enhancement of dissolution rate of poor water soluble APIs irrespective of nature and dose.
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