Lung cancer is a major public health concern, with a high incidence and fatality rate. Its treatment is very difficult, as it is mostly diagnosed in advanced stages. Non-small cell lung carcinoma (NSCLC) is the major form of lung carcinoma that persists. Brigatinib (BGT), a powerful small-molecule tyrosine kinase inhibitor, has demonstrated significant therapeutic potential in the treatment of NSCLC with anaplastic lymphoma kinase (ALK) mutations. However, the therapeutic applicability of BGT is hampered by its low solubility and bioavailability. In this study, we developed a mixed micelle system comprising Soluplus and TPGS loaded with BGT. BGT was encapsulated into the mixed micelles using various combinations of Soluplus and TPGS, with encapsulation efficiency (EE%) ranging from 52.43 ± 1.07 to 97.88 ± 2.25%. The dynamic light scattering data showed that the mixed micelles ranged in size from 75.7 ± 0.46 to 204.3 ± 5.40 nm. The selected mixed micelles (F6) showed approximately 38% BGT release in the first 2 h, and subsequently, within 72 h, the release was 94.50 ± 5.90%. The NMR experiment confirmed the formation of micelles. Additionally, the mixed micelles showed significantly higher cellular uptake (p < 0.05) and increased cytotoxicity (p < 0.05) as compared to the free BGT. Specifically, the obtained IC₅₀ values for BGT-loaded Soluplus-TPGS mixed micelles and free BGT were 22.59 ± 6.07 and 61.45 ± 6.35 μg/mL, respectively. The results of the in vitro stability experiment showed that the selected mixed micelle (F6) was stable at both room temperature and 4 °C, with only minor changes in size and PDI. Our results indicate great potential for the developed Soluplus-TPGS mixed micelles as a delivery system for BGT.

01 May 2024·Journal of Pharmaceutical and Biomedical Analysis

Development of an effective cleaning technique and ancillary analytical method for estimation of residues of selected kinase inhibitors from stainless steel and glass surfaces by swab sampling

Article

Author: Sharma, Nitish ; Rajput, Niraj ; Pillai, Megha ; Borale, Vishal Vasant ; Jadav, Tarang ; Sengupta, Pinaki ; Dhakne, Pooja

Importance of cleaning validation in the pharmaceutical industry cannot be overstated. It is essential for preventing cross-contamination, ensuring product quality & safety, and upholding regulatory standards. The present study involved development of an effective cleaning method for five selected kinase inhibitors binimetinib (BMT), selumetinib (SMT), brigatinib (BGT), capmatinib (CPT), and baricitinib (BRT). For checking the effectiveness of the developed cleaning technique, a sensitive and specific RP-HPLC based analytical method employing a diode array detector has been established to quantitate drug residue on glass and stainless steel surfaces. A reproducible swab sampling protocol utilizing TX714A Alpha swabs wetted with an extracting solvent has been developed to collect representative samples from both surfaces. Chromatographic separation of selected kinase inhibitors was achieved in gradient mode using an Agilent Zorbax eclipsed C18 column with acetonitrile and 10 mM ammonium formate as the mobile phase. The analytes were chromatographically separated in a 12 min run time. The mean swab recovery for each drug from glass and stainless steel surfaces exceeded 90%. Cleaning with IPA (70%) and acetone (70%) effectively removed residues for all five drugs. A solution comprising 10 mM SDS with 20% IPA demonstrated good efficacy in cleaning residues of BGT, BRT, and CPT, but exhibited lower efficacy for SMT and BMT.

01 Apr 2024·International Journal of Critical Illness and Injury Science

Effectiveness of backward gait training on body composition, cardiopulmonary fitness, inflammation, and metabolic marker in adults: A systematic review and meta-analysis

Review

Author: Mujaddadi, Aqsa ; Raza, Ahmar ; Nuhmani, Shibili ; Alqahatn, Abdulkarim Saeed ; Zaki, Saima ; Alnasser, Saeed Mufleh ; Alam, Md. Farhan ; Aysha, Tuba ; Sharma, Saurabh

ABSTRACTWalking is a fundamental physical activity with significant health implications. Backward gait training (BGT) has emerged as a novel approach with potential benefits, yet its effects in comparison to traditional forward gait training (FGT) remain uncertain. This systematic review and meta-analysis aimed to evaluate the effects of BGT on body composition, cardiopulmonary fitness, and inflammatory and metabolic markers in adults. A comprehensive search across electronic databases was conducted following the Preferred Publishing Items for Systematic Reviews and Meta-Analyses guidelines. Randomized clinical trials (RCTs) comparing BGT with FGT in adults were included. Methodological quality was assessed using the Cochrane risk-of-bias tool. The certainty of evidence was evaluated using the Grading of Recommendation, Assessment, Development, and Evaluation approach. The analysis included a total of 379 male participants across the studies. The meta-analysis demonstrated significant changes in body composition and inflammatory marker outcomes, which included waist-to-height ratio (standardized mean difference [SMD]-1.18, 95% confidence interval [CI]-1.89–0.48, I2 = 83%, P < 0.01), body mass index (SMD-0.55, 95% CI-0.77–0.32, I2= 0%, P < 0.01), and C-reactive protein (SMD-0.98, 95% CI–1.28-0.70, I2= 0%, P < 0.01). In addition, the qualitative review revealed potential enhancements in cardiopulmonary fitness and metabolic markers following BGT. While the results suggest potential benefits of BGT on body composition and inflammatory markers, the evidence remains limited and heterogeneous. Further robust research with diverse populations, longer intervention periods, and comprehensive outcome assessments is essential to elucidate the true impact of BGT and its utility for promoting overall health and well-being in adults.

100 Deals associated with BGT-INAD

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Neuroaxonal Dystrophies	Preclinical	GB	Bloomsbury Genetic Therapies Ltd.Startup	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

BGT-INAD

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation