Controlling hyperglycemia and avoiding glucose reabsorption are significant goals in type 2 diabetes treatments. Among the numerous modes of medication administration, the oral route is the most common. Introduction: Dapagliflozin is an oral hypoglycemic agent and a powerful, competitive, reversible, highly selective, and orally active human SGLT2 inhibitor. Dapagliflozin-loaded solid lipid nanoparticles (SLNs) are the focus of our present investigation. Controlled-release lipid nanocarriers were formulated by integrating them into lipid nanocarriers. The nanoparticle size and lipid utilized for formulation help to regulate the release of pharmaceuticals over some time. Dapagliflozin-loaded nanoparticles were formulated by hot homogenization followed by ultra-sonication. The morphology and physicochemical properties of dapagliflozin-SLNs have been characterized using various techniques. The optimized dapagliflozin-SLNs have a particle size ranging from 100.13 ± 7.2 to 399.08 ± 2.4 nm with 68.26 ± 0.2 to 94.46 ± 0.7% entrapment efficiency (%EE). Dapagliflozin-SLNs were optimized using a three-factor, three-level Box–Behnken design (BBD). Polymer concentration (X1), surfactant concentration (X2), and stirring duration (X3) were chosen as independent factors, whereas %EE, cumulative drug release (%CDR), and particle size were selected as dependent variables. Interactions between drug substances and polymers were studied using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and atomic force microscopy (AFM) analysis indicated the crystalline change from the drug to the amorphous crystal. Electron microscope studies revealed that the SLNs’ structure is nearly perfectly round. It is evident from the findings that dapagliflozin-SLNs could lower elevated blood glucose levels to normal in STZ-induced diabetic rats, demonstrating a better hypoglycemic impact on type 2 diabetic patients. The in vivo pharmacokinetic parameters of SLNs exhibited a significant rise in C_max (1258.37 ± 1.21 mcg/mL), AUC (5247.04 mcg/mL), and oral absorption (2-fold) of the drug compared to the marketed formulation in the Sprague Dawley rats.

Chronic stable angina pectoris is the primary indication for ranolazine (RZ), an anti-anginal drug. The drug has an anti-ischemic action that is unaffected by either blood pressure or heart rate. Due to the first-pass effect, the drug has a reduced bioavailability of 35 to 50%. The study emphasized developing a novel transdermal drug delivery system of nanostructured lipid carriers (NLCs) for delivering RZ. Many pharmaceutical companies employ lipid nanoparticles as biocompatible carriers for medicinal, cosmetic, and biochemical uses. These carriers are appropriate for many applications, such as topical, transdermal, parenteral, pulmonary, and oral administration, because of the large variety of lipids and surfactants that are readily available for manufacturing. RZ NLCs were made using high-pressure homogenization. Statistical analysis was utilized to find the best formula by varying the concentrations of Precirol ATO 5 (X1), oleic acid (X2), and Tween 80 (X3). Variables such as entrapment effectiveness (EE) (Y1), particle size (Y2), polydispersity index (PDI) (Y3), and zeta potential (Y4) were tested. A variety of tests were performed on the new formulation to ascertain how well it would be absorbed in the body. These tests included in vivo absorption studies, skin permeability assessments, in vitro drug release assessments, and physicochemical analyses. The particle size of RZ-NLCs was shown to be very small (118.4 ± 5.94 nm), with improved EE (88.39 ± 3.1%) and low ZP and PDI (−41.91 ± 0.38 and 0.118 ± 0.028). SEM and TEM analysis confirmed the structure of the NLCs and showed a smooth, spherical surface. Improved RZ-NLCs were used to create NLC gel, which was then tested for elasticity both physically and rheologically. The formulation’s elasticity was investigated. Optimized RZ-NLCs and NLCG were found to have transdermal fluxes of 48.369 g/cm²/h and 38.383 g/cm²/h, respectively. These results showed that the transdermal delivery of RZ distribution through NLC’s transdermal gel had more significant potential. According to in vivo experiments, the drug’s bioavailability in Wistar rats increased when it was delivered through NLCs. The findings demonstrated that NLCs loaded with RZ successfully transported the RZ to the designated site with no interruptions and that a quadratic connection existed between the independent and dependent variables.

Tyrosine kinases are known to play a role in tumour growth and proliferation, and they have become common drug targets. Tyrosine kinase inhibitors (TKIs) prohibit associated kinases from phosphorylating tyrosine residues in their substrates, preventing downstream signaling pathways from being activated. Multiple robust and well-tolerated TKIs targeting single or multiple targets, including EGFR, ALK, ROS1, HER2, NTRK, VEGFR, RET, MET, MEK, FGFR, PDGFR, and KIT, have been developed over the last two decades, contributing to our understanding of precision cancer medicine based on a patient's genetic alteration profile. The epidermal growth factor receptor (EGFR) family consists of four transmembrane tyrosine kinases (EGFR1/ErbB1, Her2/ErbB2, Her3/ErbB3, and Her4/ErbB4) and thirteen polypeptide ligands produced by them. Multiple solid tumours, including breast, pancreatic, head and neck, kidney, vaginal, renal, colon, and non-small cell lung cancer, overexpress EGFRs. Overexpression of these genes stimulates downstream signaling channels, causing cell proliferation, differentiation, cell cycle progression, angiogenesis, cell motility, and apoptosis inhibition. EGFRs' high expression and/or adaptive activation coincides with the pathogenesis and development of many tumours, making them appealing candidates for both diagnosis and therapy. Several strategies for targeting these receptors and/or the EGFR-mediated effects in cancer cells have been established. The majority of methods include the development of anti-EGFR antibodies and/or small-molecule EGFR inhibitors. This review presents the recent advances in EGFR TKIs and their role in the treatment of cancer.

The main objective of the study is to develop and optimize the potential variables which influence aripiprazole oral disintegration tablets (ODTs) formulation. Aripiprazole ODTs were prepared by using a direct compression method. Three factors with three levels of Box-Behnken design were used to optimize and develop the aripiprazole ODT formulation. The design recommended 20 formulations of different independent variables such as Microcrystalline cellulose (MCC) (Xi), Crospovidone (CP) (X2), and Cascarmellose sodium (CCS) (X3) and their effect was monitored on dependent variables such as tablet weight (Yi), Thickness (Y2), Hardness (Y3), Dissolution (Y4), Disintegration (Y5). Agreeable flow properties which are ranged from good to excellent were demonstrated by all powder blends. The disintegration time (Y5) was directly related to the lubricant concentration and mixing of time which intern had a direct effect on tablet thickness, hardness and compression force these interns had a direct impact on friability. The Box-Behnken design recommended an optimized formula of 20mg (Xi), 3mg (X2) and 3mg (X3) of the selected independent variables. Finally, the prediction error percentage responses of dependent variables Yi, Y2, Y3, Y4, and Y5 were found to be 0.38, 0.59, 2.43, 4.06, and 3.67% respectively. The 2, 4, and 10 formulas achieved more than 90% of drug release within the seven min of dissolution test time. The optimized formulation of aripiprazole ODT was successfully developed using box Behnken design and the same was prepared efficiently by using the direct compression method.

Aim: The primary goal of this study is to create a novel naproxen sodium-loaded ethosome drug delivery system for improving bioavailability, solubility and optimize using a statistical approach. Background: Naproxen sodium (i.e., a non-steroidal anti-inflammatory drug) is chosen as the first line of treatment for rheumatoid arthritis and ankylosing spondylitis. However, naproxen has side effects, such as bronchospasm, an irregular heart rhythm, etc. Therefore, adopting new drug delivery strategies when developing the dosage form is necessary and the need of the hour to prevent its side effects. The available commercial products are administered through the oral and parenteral routes, which lack bioavailability and permeability respectively. Objective: Novel ethosomal carriers were designed using Box Behnken Design (BBD) and formulation was prepared for enhanced topical delivery of naproxen sodium ethosomal gel. Methods: In order to analyze the data statistically and graphically with response surface plots, the Box-Behnken design was used to optimize the formulation variables. The independent factors were phosphatidylcholine (X1), cholesterol (X2), and ethanol (X3), while the dependent variables were entrapment efficiency (Y2), vesicle size (Y1), and PDI (Y3). The Carbopol® 940 gel was then made using the improved ethosomes. Its rheological properties, in-vitro release, ex-vivo skin penetration, and deposition were studied. Results: The best ethosomes were made by mixing phosphatidylcholine and cholesterol in a phosphate buffer at pH 7.4 with 2–5% v/v ethanol. The optimized ethosomes showed a zeta potential of -32.06 ± 0.16 mV, EE of 84.59 ± 2.38%, and a vesicular size of 105 ± 6.97 nm. Compared to the commercial products and the ethanolic solution of naproxen, these ethosomes considerably increased the amount of naproxen permeated through the skin over 24 hours. The stability of the optimized formulation was assessed for three months at room temperature, and it was found that the efficiency of the prepared novel ethosomal formulation remained intact. Conclusion: In summary, it was discovered that the ethosomal vesicles were potential carriers, showing the improved topical distribution of naproxen sodium. These findings demonstrated that using ethosomes as a transdermal medication carrier for naproxen was feasible. Compared to drug solutions, the ex-vivo permeation and skin deposition experiments produced better results.

Pirfenidone is an antifibrotic and anti-inflammatory drug used for the management of idiopathic pulmonary fibrosis. The current oral delivery of PD has multiple drawbacks, including first-pass metabolism and gastrointestinal discomfort. Efforts have been made to create nanostructured lipid carriers (NLCs) using solid lipids, liquid lipids, and surfactants through an emulsification process followed by ultrasonication to achieve sustained drug release. A central composite design (CCD) utilizing response surface methods (RSMs) was employed to develop and optimize the formulation. The assessed characteristics included particle size distribution, surface topography, drug entrapment efficiency, in vitro drug release, and kinetic profiles in animal models. Cytotoxicity experiments were performed on HepG2 and Caco-2 cell lines and compared with that of PD-NLCs. The optimized formulation yielded a particle size of 159.8 ± 3.46 nm and an encapsulation efficiency of 81.4 ± 7.1% after 10 freeze-thaw cycles of homogenized lipid carriers. In vitro tests assessing various tested flow rates revealed that over 95% of the released drug was retrieved. In vitro studies showed that the PD-loaded nanostructured lipid carrier (NLC) was more cytotoxic to HepG2 and Caco-2 cells than a pure aqueous solution of the drug. Using 25% w/w sorbitol as a cryoprotectant, the findings showed no variation in the properties of NLC before and after freeze-drying. PD-NLCs carriers were shown to have better bioavailability, longer retention time in the lung, and a 15.94-targeting factor related to the PD aqueous solution. Hence, the outcomes confirmed the potential of the PD-NLCs formulation to improve the efficacy of the drug in inhalation therapy.