Investigating the Potential of Transdermal Delivery of Avanafil Using Vitamin E-TPGS Based Mixed Micelles Loaded Films

To avoid the first-pass metabolism of avanafil (AVA) and its altered absorption in the presence of food after oral administration, this study aimed to investigate the potential of TPGS-based mixed micelle (MM)-loaded film for transdermal delivery and the enhancement of bioavailability. A Box–Behnken design was employed to optimize the permeation behavior of AVA from the transdermal film across the skin. The variables were the hydrophile-lipophile balance (HLB) of the surfactant (X1), the concentration of mixed micelles (MMs) in the film (X2), and the concentration of the permeation enhancer (X3). The initial permeation of AVA after 1 h (Y1), and the cumulative permeation of AVA after 24 h (Y2) were the dependent variables. Ex vivo studies were carried out on freshly isolated rat skin to investigate the drug’s permeation potential and results were visualized using a fluorescence laser microscope. Moreover, the pharmacokinetic behavior after a single application on male Wistar rats, in comparison with films loaded with raw AVA, was evaluated. The results showed that the optimum factor levels were 9.4% for the HLB of the surfactant used, and 5.12% MMs and 2.99% penetration enhancer in the film. Imaging with a fluorescence laser microscope indicated the ability of the optimized film to deliver the payload to deeper skin layers. Furthermore, optimized AVA-loaded TPGS-micelles film showed a significant increase (p < 0.05) in the Cmax of AVA and the area under the AVA plasma curve (approximately three-fold). The optimized AVA-loaded TPGS-MM film thus represents a successful delivery system for enhancing the bioavailability of AVA.

THYME OIL LOADED CASSAVA STARCH TRANSDERMAL FILM FOR WOUND HEALING

Biodegradable cassava starch-based transdermal film loaded with thyme volatile oil was prepared by solvent casting method for wound healing activity. The stretchability, water vapour permeability and antimicrobial properties of the film were measured. The films were evaluated for drug-excipient compatibility studies by Fourier transformed infrared spectroscopy (FTIR). The formulated film loaded with thyme volatile oil exhibited good anti-microbial activity against Staphylococcus aureus and Pseudomonas aeruginosa. The film was tested to determine its potential to increase the number of capillaries on the treated chick chorioallantoic membrane (CAM) surfaces using nine days old fertilized chick eggs. These thyme oil films loaded with cassava starch displayed angiogenic potential, which is required in the treatment of wound healing.

Transdermal Film Loaded with Garlic Oil-Acyclovir Nanoemulsion to Overcome Barriers for Its Use in Alleviating Cold Sore Conditions

The exponentially mounting cases of herpes simplex virus infection or cold sores have become a serious global concern. Acyclovir (ACV) and garlic oil (GO)-loaded lipid nanocarrier could be a promising therapeutic approach in alleviating cold sores, as well as limiting the biopharmaceutical constraints associated with ACV absorption and therapeutic efficacy. Therefore, the objective of the current research study was to formulate an ACV-GO self-nanoemulsifying drug delivery system (ACV-GO-SNEDDS) as transdermal films. The prepared SNEDDS was optimized using an experimental mixture design. The optimized ACV-GO SNEDDS was loaded in transdermal film and was evaluated for ex vivo skin permeation and in vivo pharmacokinetic prospects. An optimized ACV-GO SNEDDs formulation constituted of 10.4% (w/w) of GO, 64.8% (w/w) of surfactant mixture (Tween 20®-Span 20®); 24.8%(w/w) of co-surfactant (Propylene glycol®), and 200mg of ACV, respectively, were prepared and characterized for particle size (Y). The observed globule size of the optimized ACV-GO SNEDDS is 170 ± 13.45 nm. The results of stability studies indicated that the stability index of optimized ACV-GO-SNEDDS was more than 92 ± 3%. This optimized ACV-GO SNEDDS was loaded in hydroxypropyl cellulose transdermal film. The outcome of the ex vivo skin permeation study demonstrated a 2.3-fold augmented permeation of ACV from the optimized ACV-GO SNEDDS HPC transdermal film in comparison to the raw ACV transdermal film. There was a 3-fold increase in the relative bioavailability of the optimized ACV-GO SNEDDS transdermal film compared to the raw ACV-HPC film. The study findings confirmed that the ACV-GO SNEDDS transdermal film exhibited excellent potential to enhance the bioavailability of ACV.

Two-Step Optimization to Develop a Transdermal Film Loaded With Dapoxetine Nanoparticles: A Promising Technique to Improve Drug Skin Permeation

Dapoxetine (DPX) is an orally administered drug for the treatment of premature ejaculation (PE). One of the challenges of administering DPX orally as a tablet is its poor bioavailability (ie, 42%) due to extensive first-pass metabolism. Thus, it is vital to develop a new formulation and mode of delivery to achieve the unmet needs of PE treatment. In this study, an optimized DPX polymeric nanoparticle (PNP) was developed and subsequently loaded into a transdermal film. The Box–Behnken design was utilized to optimize 3 formulation factors affecting the particle size and entrapment efficiency (EE) of chitosan (CS)-alginate (ALG) PNPs. A 3-level factorial design was used to study the effect of 2 variables affecting DPX cumulative percent released and percent elongation from transdermal films loaded with DPX-PNPs. Permeation parameters were calculated following ex vivo permeation study through rat skin. Transport of the PNPs across the skin layers was investigated using a fluorescence laser microscope. Results revealed that an optimized PNPs formulation was developed with a particle size 415.94 nm and EE 37.31%. Dapoxetine was successfully entrapped in the polymeric matrix. Chitosan and ALG interacted electrostatically with the studied cross-linking agents to form a polyelectrolyte complex. The ex vivo study illustrated a sustained release profile of DPX with enhanced skin permeation from the film loaded PNPs. Moreover, the PNPs was able to penetrate deeper into skin layers. Therefore, DPX transdermal film developed in this work could be considered as a successful drug delivery with better patient compliance for the treatment of PE.

LC-MS/MS determination of avanafil and its metabolites in rat plasma and brain: pharmacokinetic study after oral administration and transdermal film application

A pioneering bioanalytical LC-MS/MS method was developed for monitoring avanafil and its metabolites in rat plasma and brain after oral administration and transdermal application.