The ideal drug delivery system has a bioavailability comparable to parenteral dosage forms but is as convenient and easy to use for the patient as oral solid dosage forms. In recent years, there has been increased interest in transdermal drug delivery (TDD) as a non-invasive delivery approach that is generally regarded as being easy to administer to more vulnerable age groups, such as paediatric and geriatric patients, while avoiding certain bioavailability concerns that arise from oral drug delivery due to poor absorbability and metabolism concerns. However, despite its many merits, TDD remains restricted to a select few drugs. The physiology of the skin poses a barrier against the feasible delivery of many drugs, limiting its applicability to only those drugs that possess physicochemical properties allowing them to be successfully delivered transdermally. Several techniques have been developed to enhance the transdermal permeability of drugs. Both chemical (e.g., thermal and mechanical) and passive (vesicle, nanoparticle, nanoemulsion, solid dispersion, and nanocrystal) techniques have been investigated to enhance the permeability of drug substances across the skin. Furthermore, hybrid approaches combining chemical penetration enhancement technologies with physical technologies are being intensively researched to improve the skin permeation of drug substances. This review aims to summarize recent trends in TDD approaches and discuss the merits and drawbacks of the various chemical, physical, and hybrid approaches currently being investigated for improving drug permeability across the skin.

The objective of this study was to investigate the pH-dependent solubility and dissolution of weakly basic Biopharmaceutical Classification Systems (BCS) class II drugs, characterized by low solubility and high permeability, using carvedilol, a weak base with a pK _a value of 7.8, as a model drug. A series of solubility and in vitro dissolution studies was carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH range of the GI from 1.2 to 7.8. The effect of ionic strength, buffer capacity, and buffer species of the dissolution media on the solubility and dissolution behavior of carvedilol was also investigated. The study revealed that carvedilol exhibited a typical weak base pH-dependent solubility profile with a high solubility at low pH (545.1–2591.4 μg/mL within the pH range 1.2–5.0) and low solubility at high pH (5.8–51.9 μg/mL within the pH range 6.5–7.8). The dissolution behavior of carvedilol was consistent with the solubility results, where carvedilol release was complete (95.8–98.2% released within 60 min) in media simulating the gastric fluid (pH 1.2–5.0) and relatively low (15.9–86.2% released within 240 min) in media simulating the intestinal fluid (pH 6.5–7.8). It was found that the buffer species of the dissolution media may influence the solubility and consequently the percentage of carvedilol released by forming carvedilol salts of varying solubilities. Carvedilol solubility and dissolution decreased with increasing ionic strength, while lowering the buffer capacity resulted in a decrease in carvedilol solubility and dissolution rate.

Green synthesis of zinc oxide (ZnO) nanoparticles (NPs) using various plant extracts as reducing and capping agents has gained attention in recent research. The green synthesis of ZnO NPs offers several advantages such as being simple, eco-friendly, safe, cost-effective, and reproducible approach with high stability. Hence, this article provides an overview of zinc metal and ZnO compounds, and traditional chemical and physical synthesis of ZnO NPs with primary focuses on the green synthesis of ZnO NPs. This study discusses various plant extracts used and the proposed mechanisms in the green synthesis of ZnO NPs. Additionally, it explores the cytotoxic mechanisms of the green-synthesized ZnO NPs and addresses the various biomedical applications of ZnO NPs, including antibacterial, anticancer, antidiabetic, antioxidant, antifungal, antiviral, antiparasitic, anti-inflammatory, and wound healing. Moreover, the review critically discusses the toxicity of ZnO NPs and emphasizes the need for more toxicological studies to ensure the safety and facilitate the risk assessments and risk management of ZnO NPs. Furthermore, this review underlines the challenges associated with the translation process of ZnO NPs from bench to market, including the complex and time-consuming regulatory approval process for ZnO NPs, which requires a multidisciplinary approach involving scientists, regulators, and manufacturers.

Periodontal disease is a chronic inflammation of gum and tissues that surround and support the teeth. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be used in the treatment of periodontitis to ease swelling and inflammation. One approach of treating periodontitis is loading the NSAIDs in local drug delivery systems. Therefore, the objective of this study was to investigate the local delivery of the NSAIDs model drug ibuprofen to treat periodontitis using different types of gel formulations (hydrogel, oleogel, and bigel). Gel formulations were characterized in terms of their rheological properties (flow behavior, viscoelastic, and bioadhesive properties) using a controlled-stress rheometer. The in vitro drug release of ibuprofen from gel formulations was investigated using Franz diffusion cells. Gels exhibited more solid-like (elastic) behavior. The viscosity and viscoelastic properties were in the order of oleogel > bigel > hydrogel, respectively. In bioadhesion study, mucin dispersion/plain ibuprofen-hydrogel mixture showed a frequency-dependent interaction of ΔG’ = −31 and ΔG’ = + 53 Pa at 1 and 10 rad/s, respectively. A strong positive interaction (ΔG’ = + 6000 and +130,667 Pa at 1 and 10 rad/s, respectively) was found in mucin dispersion/plain ibuprofen–oleogel mixture. The extent of the negative interaction increased in mucin dispersion/plain ibuprofen-bigel mixture (ΔG’ = −59,000 and −79,375 Pa at 1 and 10 rad/s, respectively). After 6 h, ibuprofen release from hydrogel, oleogel, and bigel was 59.5 ± 2.2, 80.6 ± 3.9, and 94.6 ± 3.2%, respectively. Results showed that the rheological and bioadhesive properties and in vitro drug release were influenced by the type of gel formulations.

Chronic oral administration of the non-steroidal anti-inflammatory drug, diclofenac diethylamine (DDEA), is often associated with gastrointestinal ulcers and bleeding. As an alternative to oral administration, a nanoemulsion-based gel (NE gel) formulation of DDEA was developed for topical administration. An optimized formulation for the o/w nanoemulsion of oil, surfactant and cosurfactant was selected based on nanoemulsion mean droplet size, clarity, stability, and flowability, and incorporated into the gelling agent Carbopol® 971P. Rheological studies of the DDEA NE gel were conducted and compared to those of conventional DDEA gel and emulgel. The three gels exhibited an elastic behavior, where G′ dominated G″ at all frequencies, indicating the formation of strong gels. NE gel exhibited higher G′ values than conventional gel and emulgel, which indicated the formation of a stronger gel network. Strat-M® membrane, a synthetic membrane with diffusion characteristics that are well correlated to human skin, was used for the in vitro diffusion studies. The release of DDEA from conventional gel, emulgel and NE gel showed a controlled release pattern over 12 h, which was consistent with the rheological properties of the gels. DDEA release kinetics from the three gels followed super case II transport as fitted by Korsmeyer–Peppas model.