Box-Behnken Design: Optimization of Proanthocyanidin-Loaded Transferosomes as an Effective Therapeutic Approach for Osteoarthritis.

Transferosomes are one of the vesicular carriers that have received extensive research and attention recently because of their capacity to get beyond the barriers posed by the stratum corneum to penetration. The intent of the current study is to optimize and evaluate proanthocyanidin (PAC) containing transferosomal transdermal gels. PAC-containing transferosomes were prepared using the film hydration method and then loaded into a 4% methylcellulose gel. A 23 Box-Behnken design was used to optimize the PAC-loaded transferosomal gel, where the effects of phospholipid 90 G (X1), Tween 80 (X2), and sonication time (X3) were evaluated. The formulation factors, such as the drug entrapment efficiency percentage (PEE) and in vitro drug release, were characterized. A PEE of 78.29 ± 1.43% and a drug release in vitro at 6 h of 24.2 ± 1.25% were obtained. The optimized transferosomal-loaded proanthocyanidin (OTP) formulation penetrated the porcine skin at an excellent rate (0.123 ± 0.0067 mg/cm2/h). Stability tests were conducted for OTP to predict the effects of various temperature conditions on the physical appearance, drug content, and PEE for periods of 15, 30, and 45 days. Finally, this transferosomal system for transdermal PAC delivery may be a suitable alternative to the conventional treatment for osteoarthritis.

The Race to Replace PDE5i: Recent Advances and Interventions to Treat or Manage Erectile Dysfunction: Evidence from Patent Landscape (2016-2021).

For a few decades, globally, erectile dysfunction (ED) has become more prominent even in young adults and represents a mounting health concern causing a significant effect on men's quality of life. There is an expectation that by the end of 2025, the number of ED cases can rise to 322 million. We aimed to comprehensively analyze the scientific output of scholarly articles and studies in the field of ED (2016-2021). Data from scholarly articles were collected using Pubmed, and clinical trials-related information was accessed from the clinical trials website. An extensive patent search was conducted using databases such as USPTO (United States patent and trademark office) and EPO (European patent office), WIPO (World Intellectual Property Organization), etc. Owing to the high market value of ED drugs, considerable interest was attained to grab the opportunities. The race to replace the phosphodiesterase type 5 inhibitor (PDE5 inhibitor-PDE5i) can be identified as evident from the significant number of patents filed and the inventions cleared with clinical trials. Some other intriguing interventions are identified for ED treatment but have yet to gain public acceptance. The current analysis confirms the overall evolution and unexplored corners of research on ED treatment strategies with a current global projection.

Development of Nanocrystal Compressed Minitablets for Chronotherapeutic Drug Delivery.

The present work aimed to develop a chronotherapeutic system of valsartan (VS) using nanocrystal formulation to improve dissolution. VS nanocrystals (VS-NC) were fabricated using modified anti-solvent precipitation by employing a Box−Behnken design to optimize various process variables. Based on the desirability approach, a formulation containing 2.5% poloxamer, a freezing temperature of −25 °C, and 24 h of freeze-drying time can fulfill the optimized formulation's requirements to result in a particle size of 219.68 nm, 0.201 polydispersity index, and zeta potential of −38.26 mV. Optimized VS-NC formulation was compressed (VNM) and coated subsequently with ethyl cellulose and HPMC E 5. At the same time, fast dissolving tablets of VS were designed, and the best formulation was loaded with VNM into a capsule size 1 (average fill weight­400−500 mg, lock length­19.30 mm, external diameter: Cap­6.91 mm; Body­6.63 mm). The final tab in cap (tablet-in-capsule) system was studied for in vitro dissolution profile to confirm the chronotherapeutic release of VS. As required, a bi-pulse release of VS was identified with a lag time of 5 h. The accelerated stability studies confirmed no significant changes in the dissolution profiles of the tab in cap system (f2 similarity profile: >90). To conclude, the tab in cap system was successfully developed to induce a dual pulsatile release, which will ensure bedtime dosing with release after a lag-time to match with early morning circadian spikes.

Preparation, in-vitro and in-vivo characterization of transdermal patch containing glibenclamide and atenolol: a combinational approach.

A novel aspiration in treatment of chronic disease like diabetes associated with other non communicable disease risk factors, such as hypertension is to provide greater therapeutic effect, overcome the side effects by complex therapeutic regimen and to improve patient compliance upon administering combinational transdermal delivery of Glibenclamide (G) and Atenolol (A) which have not been tested literally. Hence, the present study was designed to develop a transdermal patch containing Glibenclamide and Atenolol using blends of different polymeric combinations such as Hydroxy propyl methyl cellulose (HPMC), Poly vinyl pyrolidone (PVP) and Carbopol (CP). The patches were subjected to physicochemical parameters, in-vitro and in-vivo drug release and in-vitro skin permeation studies. Good results were obtained in all the evaluated parameters. The drug release of all formulation follows zero order kinetics by diffusion mechanism of non fickian diffusion type. In-vitro transdermal permeation studies by using rat & goat skin and finally in-vivo studies by using rabbits were carried out for the optimized formulation (GA4 HPMC 1%, PVP 0.5%, CP 0.5%). The developed transdermal delivery system containing Glibenclamide & Atenolol might be a milestone in the combinational therapy of diabetes and hypertension.