Pharmacokinetic Evaluation of a Novel Donepezil-Loaded Dissolving Microneedle Patch in Rats

Research on the development of dissolving microneedles (DMNs) has focused on bolus drug delivery, with little attention on sustained release. Here, we evaluated the sustained release, absorption pattern, and effective drug permeation of a novel donepezil-loaded DMN patch through an in vivo investigation on rats. The applications of DMN patches to the shaved skin of rats for 1 week and 1 h were compared with oral donepezil administration to assess their sustained release capabilities. We used a validated liquid chromatography–tandem mass spectrometry method to quantify donepezil in the plasma. We found that the microneedle arrays effectively delivered donepezil across the skin, with dissolution observed within 1 h of application. Furthermore, skin irritation test showed that the patches produced no irritation response. The DMN arrays also effectively increased drug permeation and demonstrated sustained release and absorption of donepezil from DMN patches. These patches allow extended dosing intervals, reduced gastrointestinal adverse effects, and convenient self-administration to mitigate poor drug compliance, making them beneficial for the treatment of elderly patients with Alzheimer’s disease.

Controlled Transdermal Iontophoresis of Insulin from Water-Soluble Polypyrrole Nanoparticles: An In Vitro Study

The iontophoresis delivery of insulin (INS) remains a serious challenge due to the low permeability of the drug through the skin. This work aims to investigate the potential of water-soluble polypyrrole nanoparticles (WS-PPyNPs) as a drug donor matrix for controlled transdermal iontophoresis of INS. WS-PPyNPs have been prepared via a simple chemical polymerization in the presence of sodium dodecyl sulfate (SDS) as both dopant and the stabilizing agent. The synthesis of the soluble polymer was characterized using field emission scanning electron microscopy (FESEM), dynamic light scattering (DLS), fluorescence spectroscopy, and Fourier transform infrared (FT–IR) spectroscopy. The loading mechanism of INS onto the WS-PPyNPs is based on the fact that the drug molecules can be replaced with doped dodecyl sulfate. A two-compartment Franz-type diffusion cell was employed to study the effect of current density, formulation pH, INS concentration, and sodium chloride concentration on anodal iontophoresis (AIP) and cathodal iontophoresis (CIP) of INS across the rat skin. Both AIP and CIP delivery of INS using WS-PPyNPs were significantly increased compared to passive delivery. Furthermore, while the AIP experiment (60 min at 0.13 mA cm–2) show low cumulative drug permeation for INS (about 20.48 µg cm−2); the CIP stimulation exhibited a cumulative drug permeation of 68.29 µg cm−2. This improvement is due to the separation of positively charged WS-PPyNPs and negatively charged INS that has occurred in the presence of cathodal stimulation. The obtained results confirm the potential applicability of WS-PPyNPs as an effective approach in the development of controlled transdermal iontophoresis of INS.

IN-SITU FILM-FORMING SOLUTION FOR TOPICAL APPLICATION OF TERBINAFINE HCL: BIOPHARMACEUTICAL EVALUATION AND IN VIVO ANTIFUNGAL PERFORMANCE USING ANIMAL MODEL

Objective: The main purpose of this study is to develop a film-forming solution with optimum physical-mechanical characteristics and excellent antifungal activity to enhance deposition and penetration into the stratum corneum (SC). Methods: The film-forming solutions of terbinafine HCl were formulated using methacrylate copolymers, polyethylene glycol 400, and ethanol as diluent. The selected formulations were subjected to test of physical-mechanical properties, drug release, drug permeation across the stratum corneum and drug deposition study. The best formulation was further evaluated for in vivo antifungal efficacy. Results: The selected formulations exhibited superior pharmaceutical characteristics, including rapid drying, non-stickiness, and being transparency on the skin. Formulation A (FA) had significantly lower tensile strength (4.78 N/m2, p<0.05) and higher percentage elongation at break (33.61%, p<0.05), which reduced the firmness of the film, allowing it to be super-flexible in following the movement of the skin and preventing loss of film through abrasion. FA showed significantly (p<0.05) rapid drug permeation (1510.51 µg/cm2) across the stratum corneum (SC) at 24 h when compared with the other formulations and the positive control proprietary drug (PD), Terbex® cream formulation (475.8 µg/cm2). Conclusion: Having superior physical-mechanical and drug permeation characteristics, FA can be considered as an efficient, reproducible, and efficacious antifungal formulation for topical application.

Metformin hydrochloride entrapment in sorbitan monostearate for intestinal permeability enhancement and pharmacodynamics

Penetration enhancement of metformin hydrochloride via its molecular dispersion in sorbitan monostearate microparticles is reported. This represents basic philosophy to maximize its entrapment for maximum penetration effect. Drug dispersion in sorbitan monostearate with different theoretical drug contents (TDC) were prepared. Products showed excellent micromeritics and actual drug content (ADC) increased by increasing TDC. The partition coefficient of the drug products showed huge improvement. This indicates the drug entrapped in the polar part of sorbitan monostearate as a special image which effects on the drug release. The drug permeation profiles from the different products are overlapped with nearly equal permeation parameters. The permeation results suggested the main driving force for improving the drug paracellular pathway is its dispersion in sorbitan monostearate and is independent of ADC. Pharmacodynamic of the products showed a significant improvement than the drug alone at p ˂ 0.05. ANOVA test indicated the insignificant pharmacodynamic difference between the low, middle, and high ADC of the products. An excellent correlation founded between the drug permeation and pharmacodynamic precents. Drug permeation driving force via the paracellular pathway is its entrapment in sorbitan monostearate and independent on ADC. The technique is simple and the products had excellent micromeritics.

Human Skin Permeation Enhancement Using PLGA Nanoparticles Is Mediated by Local pH Changes

The steady improvement and optimization of transdermal permeation is a constant and challenging pharmaceutical task. In this study the influence of poly(lactide-co-glycolide) (PLGA) nanoparticles on the dermal permeation of the anti-inflammatory drug flufenamic acid (FFA) was investigated. For this aim, different vehicles under non-buffered and buffered conditions and different skin models (human heat separated epidermis and reconstructed human epidermis equivalents) were tested. Permeation experiments were performed using static Franz diffusion cells under infinite dosing conditions. Already the presence of drug-free nanoparticles increased drug permeation across the skin. Drug permeation was even enhanced when applying drug-loaded nanoparticles. In contrast, buffered vehicles with different pH values (pH 5.4–7.4) revealed the influence of the pH on the permeation of FFA. The change of the surrounding pH of the biodegradable nanoparticulate system was demonstrated and visualized using pH-sensitive fluorescent probes. While a potential contribution of hair follicles could be ruled out, our data suggest that the enhanced permeation of FFA through human skin in the presence of PLGA nanoparticles is mediated by a locally decreased pH during hydrolytic degradation of this polymer. This hypothesis is supported by the observation that skin permeation of the weak base caffeine was not affected.

Polyvinyl alcohol/cellulose hydrogel as possible corneal stroma substitute in drug permeation tests

The permeation studies of active compounds and formulations are necessary to verify the capability of molecules to pass through the physiological barrier of our body. In order to develop a 3D model of the cornea, preparation and characterization of different hydrogels as corneal stroma substitutes were tested.