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 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 weight—400–500 mg, lock length—19.30 mm, external diameter: Cap—6.91 mm; Body—6.63 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.

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.

There are many circumstances where chronic disease is associated with other disorders, especially in diseases such as diabetes with noncommunicable disease risk factors, such as hypertension. The current therapies for treating such chronic comorbid diseases are limited and challenging due to the difficulties in overcoming the side effects from complex therapeutic treatment regimen. The present study is aimed to develop and optimize the combinational nano invasomal gel of Glibenclamide (GLB) and Atenolol (ATN) as a novel combination therapy for comorbid treatment of diabetic hypertensive patients. The developed formulations were characterized for various parameters, including in-vitro skin permeation, skin irritation, in-vivo antidiabetic, and antihypertensive activities. OCNIG showed that the % entrapment efficiency of GLB is 96.67 ± 0.65% and % entrapment efficiency of ATN is 93.76 ± 0.89%, flux of GLB (240.43 ± 1.76 μg/cm2/h), and flux of ATN (475.2 ± 1.54 μg/cm2/h) which was found to conform to the expected value. The results indicated desired release and permeation profiles. Optimized formulation showed significant pharmacokinetic properties, which shows improvement in bioavailability by 134.30% and 180.32% respectively for two drugs, when compared to marketed oral preparation. Pharmacodynamic studies showed improved and prolonged management of diabetes and hypertension in Wistar rats, compared to oral and drug-loaded nano invasomes formulations. Overall, the results showed that nano invasomal gel was found to be a useful and promising transdermal delivery system for the treatment of concurrent diseases.

There are numerous circumstances where chronic disease is associated with other disorders, especially in diseases like diabetes with noncommunicable disease risk factors, such as hypertension. This study shows a novel and innovative combinational proniosomal delivery of combination to beat the reactions by complex therapeutic regimen, and to improve patient compliance after controlling combinational transdermal delivery of Glibenclamide (GLB) and Atenolol (ATN) which have not been tried actually. To achieve the above reason, proniosomes were prepared and optimized utilizing Box-Behnken design. The ideal formulation was chosen by a point prediction method and formulation showed vesicle size of 562 ± 1.223 nm, entrapment efficiency of GLB & ATN 97.037 ± 1.43% and 96.230 ± 1.62% respectively which were found in concurrence with the predicted value. The optimized combinational proniosomal gel (OCPG) formulation was additionally assessed for in vitro drug release, In vitro drug permeation, and in vivo pharmacokinetic study. The OCPG formulation shows the greatest flux over the rabbit skin (128.609 ± 2.24 mg/cm2/h and 322.054 ± 1.53 mg/ cm2/h) of GLB and ATN respectively. The results indicated desired release and permeation profiles. OCPG showed significantly (p < 0.001) pharmacokinetic contemplate exhibited that transdermal proniosomal formulation demonstrated improvement in bioavailability of two drugs 129.30 and 174.62 times respectively as that of the oral formulation. Overall the results show that controlled release GLB and ATN provesicles offer a useful and promising transdermal delivery system for the treatment of type II diabetes and hypertension by using design. Henceforth this may be an achievement in treating diabetic hypertensive patient.