Comparative bioequivalence studies of tramadol hydrochloride sustained-release 200 mg tablets

Suhas S Khandave1, Satish V Sawant1, Santosh S Joshi1, Yatish K Bansal2, Sonal S Kadam21Accutest Research Laboratories (I) Private Limited, Koparkhirne, Navi Mumbai, Maharashtra, India; 2Ipca Laboratories Limited, Kandivli Mumbai, Maharashtra, IndiaBackground: Tramadol hydrochloride is available as 50 mg immediate-release (IR) and 100 mg, 200 mg, and 300 mg sustained-release (SR) tablets. The recommended dose of tramadol is 50–100 mg IR tablets every 4–6 hours. The tramadol SR 200 mg tablet is a better therapeutic option, with a reduced frequency of dosing, and improved patient compliance and quality of life. The present study evaluated the bioequivalence of a generic tramadol SR 200 mg tablet.Methods: A comparative in vitro dissolution study was performed on the test and reference products, followed by two separate single-dose bioequivalence studies under fasting and fed conditions and one multiple-dose bioequivalence study under fasting conditions. These bioequivalence studies were conducted in healthy human subjects using an open-label, randomized, two-treatment, two-period, two-sequence, crossover design. The oral administration of the test and reference products was done on day 1 for both the single-dose studies and on days 1–5 for the multiple-dose study in each study period as per the randomization code. Serial blood samples were collected at predefined time points in all the studies. Analysis of plasma concentrations of tramadol and O-desmethyltramadol (the M1 metabolite) was done by a validated liquid chromatography-mass spectrometry analytical method. The standard acceptance criterion of bioequivalence was applied on log-transformed pharmacokinetic parameters for tramadol and its M1 metabolite.Results: The ratios for geometric least-square means and 90% confidence intervals were within the acceptance range of 80%–125% for log-transformed primary pharmacokinetic parameters for tramadol and its M1 metabolite in all the three studies.Conclusion: The test product is bioequivalent to the reference product in terms of rate and extent of absorption, as evident from the single-dose and multiple-dose studies. Both the treatments were well tolerated.Keywords: tramadol, multiple-dose, steady state, bioequivalenc

Effect of CNT-based resin modification on the mechanical properties of polymer composites

In this study an attempt was made to explore the possibility of substituting 3D E-glass fabric with eco-friendly basalt fabric along with the modification of resin using MWCNTs, a material system about which very limited information exists. The study involved comparing the mechanical properties of two sets of composites. The first set was comprised of 3D orthogonally woven E-glass-reinforced epoxy composites, basalt-reinforced epoxy composites, and hybrid 3D E-glass orthogonally woven/basalt-reinforced epoxy composites while the second set of composites was the same as the first but prepared with resin modified with Multi Walled Carbon Nanotubes (MWCNTs). All the composites were fabricated by hand lay-up and compression molding techniques. To modify the resin for the second set of composites, MWCNTs were dispersed into the epoxy resin with acetone as a surfactant by magnetic stirring and ultra-sonification. Mechanical tests included tensile, flexural, and low velocity impact strength which were evaluated as per standards. Scanning electron microscopy (SEM) was employed to study the fractured surfaces. Results showed that resin modification did not yield any positive results on the mechanical properties of the composites. The highest tensile (364.4 MPa) and flexural strength (345.3 MPa) was obtained for 3D E-glass composites followed by basalt composites and hybrid 3D E-glass/basalt composites while the highest impact strength of 198.42 kJ/m2 was exhibited by the hybrid 3D E-glass/basalt composites. SEM micrographs showed de-bonding between the modified matrix and fiber which was seen as one of the primary causes for relatively poor performance of the composites prepared with modified resin. Fiber breakage, matrix cracking, fiber pull-out, and delamination were the other modes of failure. Results suggest that hybridization with basalt fibers is a much safer, more cost effective, and eco-friendly option over resin modification

Influence of fabric orientation and compression factor on the mechanical properties of 3D E-glass reinforced epoxy composites

3-D E-glass fabric reinforced epoxy composites at 6 mm thickness were fabricated for various orientations of the binder yarn viz. 0°, 30°, 45°, 60° and 90° respectively. Tensile, flexural, interlaminar shear stress tests were conducted to ascertain the influence of binder yarn orientation on the mechanical properties of the composites. The composites with 0° binder yarn orientation showed the best strength followed by 90° whilst the others showed highly depleted traits in comparison. Shear stress induced at the interface of each lamina was seen as the major reason for drop in the strength. A secondary study was carried out to explore the effect of compression factor during fabrication on the mechanical properties of the composites. Laminates with varying thickness namely, 4 mm, 5 mm and 7 mm but, with same number of plies of 3D E-glass fabric at 0° orientation were fabricated. The test results were compared with the results of 6 mm composites from the primary study. The results showed that, compression factor affected the mechanical properties of the composites and had a direct relation with increasing compression factor up to a certain value beyond which a drop in properties was seen. Composites pressed to a thickness of 5 mm showed the best properties. Drop in properties was attributed to close packing of reinforcement and crushing of fibres leading to inefficient stress transfer. Scanning electron microscopy was employed to understand the modes of failure. The major failure modes observed were delamination, matrix cracking and debonding. Based on the results obtained, these composites can be seen as a material system for applications like ballistic armours, structural renovations and automobile components

DIGITAL RIGHTS MANAGEMENTSOLUTIONS FOR ENTERPRIZES:AN OVERVIEW

In 21stcentury the digitalization of the processes and information has taken place very rapidly. Every organization in the competitive era has the confidential information and processes. The success of every organization is based on the security of such secret data and information.Confidential data, information, processes plays a vital role in development of the enterprise, in order to withstand in this market with a huge business competitors.Security of such information is really a challenge and many researchers have tried addressing this problem in last decade.Theft of such data may include the product development information, research data, business plans, financial details, list of the customers. It has been observedin the research that most of the times suchdata is stolen by insiders.Authors have tried to present the overview of various solutions proposed by researchers in past decade

Laparoscopic subcutaneous onlay mesh repair for ventral hernia: Our early experience

Introduction: Repair of the ventral hernia is an ongoing challenge in surgery, and a number of surgical techniques have been developed ranging from direct suturing techniques to the use of various mesh types in different planes of the abdominal wall to close the defect and strengthen the musculofascial tissue. Laparoscopic subcutaneous onlay mesh (SCOM) repair is a novel procedure developed recently for ventral hernia repair. We would like to share our experience with laparoscopic SCOM repair. Patients and Methods: This is a prospective observational study of patients who have undergone ventral hernia repair at Bangalore Endoscopic Surgery Training Institute and Research Centre from June 2020 to June 2022. A total of 20 patients are included in this study. Statistical Analysis Used: The data were entered into MS Excel and analysed. Results: A total of 20 patients underwent SCOM repair with a defect size measuring up to 8 cm × 8 cm and a mean operative time of 117 min. Three patients had seroma formation and one patient had surgical site infection. No recurrence is seen after 1-year 2-month follow-up. Conclusion: SCOM repair is the newer approach to ventral hernia repair with the advantage over open onlay mesh repair in terms of less pain and better cosmesis. SCOM repair avoids intraperitoneal dissection which may lead to visceral injuries as well as subsequent intraperitoneal adhesions. The acceptance of such surgeries would depend on further long-term studies

Interleukin-3 enhances the migration of human mesenchymal stem cells by regulating expression of CXCR4

Abstract Background Mesenchymal stem cells (MSCs) represent an important source for cell therapy in regenerative medicine. MSCs have shown promising results for repair of damaged tissues in various degenerative diseases in animal models and also in human clinical trials. However, little is known about the factors that could enhance the migration and tissue-specific engraftment of exogenously infused MSCs for successful regenerative cell therapy. Previously, we have reported that interleukin-3 (IL-3) prevents bone and cartilage damage in animal models of rheumatoid arthritis and osteoarthritis. Also, IL-3 promotes the differentiation of human MSCs into functional osteoblasts and increases their in-vivo bone regenerative potential in immunocompromised mice. However, the role of IL-3 in migration of MSCs is not yet known. In the present study, we investigated the role of IL-3 in migration of human MSCs under both in-vitro and in-vivo conditions. Methods MSCs isolated from human bone marrow, adipose and gingival tissues were used for in-vitro cell migration, motility and wound healing assays in the presence or absence of IL-3. The effect of IL-3 preconditioning on expression of chemokine receptors and integrins was examined by flow cytometry and real-time PCR. The in-vivo migration of IL-3-preconditioned MSCs was investigated using a subcutaneous matrigel-releasing stromal cell-derived factor-1 alpha (SDF-1α) model in immunocompromised mice. Results We observed that human MSCs isolated from all three sources express IL-3 receptor-α (IL-3Rα) both at gene and protein levels. IL-3 significantly enhances in-vitro migration, motility and wound healing abilities of MSCs. Moreover, IL-3 preconditioning upregulates expression of chemokine (C-X-C motif) receptor 4 (CXCR4) on MSCs, which leads to increased migration of cells towards SDF-1α. Furthermore, CXCR4 antagonist AMD3100 decreases the migration of IL-3-treated MSCs towards SDF-1α. Importantly, IL-3 also induces in-vivo migration of MSCs towards subcutaneously implanted matrigel-releasing-SDF-1α in immunocompromised mice. Conclusions The present study demonstrates for the first time that IL-3 has an important role in enhancing the migration of human MSCs through regulation of the CXCR4/SDF-1α axis. These findings suggest a potential role of IL-3 in improving the efficacy of MSCs in regenerative cell therapy

Experimental investigation into mechanical properties of coconut shell powder modified epoxy/ 3d E-glass composites

The aim of this research work was to investigate the influence of resin modification with Coconut Shell Powder (CSP) on the tensile, flexural and impact properties of composites reinforced with 3D E-glass orthogonally woven fabric. The composites were fabricated using a combination of hand lay-up and press moulding techniques. Three different proportion of CSP namely, 0.5%, 1.5% and 3% by weight of resin were considered for modifying the epoxy resin. The properties of these composites were determined and compared with composites fabricated without coconut shell powder. Additionally, to ascertain the effect of dispersion technique on the mechanical properties of the composites, their tensile strengths were compared with composites fabricated with epoxy in which CSP was added to the resin and mixed mechanically. Improved mechanical properties were obtained for composites fabricated with modified resin and an increasing trend was observed with increase in proportion of CSP with the highest properties obtained for composites with 3% CSP content showing an increase of about 117%, 87% and 39% in tensile, flexural and impact strengths respectively over the composites without CSP. Tensile strengths of composites prepared by mechanical dispersion of CSP were lower than the resin modified composites having the same CSP content, showing a drop of about 53% and 25% thereby proving the efficacy of resin modification process. Scanning Electron Microscopy (SEM) was employed to analyse the characteristics of the CSP and to investigate the various failure modes

Additional file 1: of Interleukin-3 enhances the migration of human mesenchymal stem cells by regulating expression of CXCR4

Includes supplementary methods, Figure S1 showing effect of IL-3 on expression of human MSC surface markers, Figure S2 showing effect of IL-3 on proliferation of human MSCs, Table S1 presenting hematological parameters of mice infused with IL-3-treated MSCs and Figure S3 showing tumorigenicity assay of human MSCs pretreated with IL-3. (DOCX 1519 kb