Enhancement of skin localization of ß-carotene from red fruit (Pandanus conoideus Lam.) using solid dispersion-thermoresponsive gel delivered via polymeric solid microneedles.

Red fruit (Pandanus conoideus Lam.) boasts high ß-carotene (BC) content, often consumed orally. However, absorption issues and low bioavailability due to food matrix interaction have led to transdermal delivery exploration. Nevertheless, BC has a short skin retention time. To address these limitations, this study formulates a ß-carotene solid dispersion (SD-BC) loaded thermoresponsive gel combined with polymeric solid microneedles (PSM) to enhance in vivo skin bioavailability. Characterization of SD-BC includes saturation solubility, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and in vitro release. Characterization of SD-BC thermoresponsive gel includes gelation temperature, viscosity, rheological behaviour, pH, bio-adhesiveness, spreadability, and extrudability. PSM's mechanical properties and insertion capability were assessed. Ex vivo and in vivo dermato-pharmacokinetic studies, drug content, hemolysis, and skin irritation assessments were conducted to evaluate overall performance. Results confirm amorphous SD-BC formation, enhancing solubility. Both SD-BC thermoresponsive gel and PSM exhibit favourable characteristics, including rheological properties and mechanical strength. In vitro release studies showed a seven-fold increase in BC release compared to plain hydrogel. SD-BC thermoresponsive gel combined with PSM achieves superior ex vivo permeation (Cmax = 305.43 ± 32.07 µg.mL-1) and enhances in vivo dermato-pharmacokinetic parameters by 200-400 %. Drug content, hemolysis, and skin irritation studies confirmed its safety and non-toxicity.

Hydrogel forming microneedle-mediated transdermal delivery of sildenafil citrate from polyethylene glycol reservoir: An ex vivo proof of concept study.

Erectile dysfunction (ED) is a disorder that often occurs in men worldwide. One of the drugs used as the first-line therapy for erectile dysfunction is sildenafil citrate (SC). Unfortunately, SC was commonly found in oral, injection, and transdermal dosage forms with some limitations, mainly related to low oral bioavailability caused by the occurrence of first-pass metabolism in the liver, and poor patient comfort and compliance. Therefore, it was essential to develop dosage forms to overcome these limitations. We developed hydrogel-forming microneedles (HFM) that can facilitate transdermal delivery of SC by penetrating the stratum corneum. HFM was made using polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) as polymers and several variations of tartaric acid as crosslinking agents. The evaluation of swelling properties, mechanical resistance, and penetration ability showed that the HFM produced had good insertion properties and swelling capabilities ranging from 300% to 700%. This HFM was designed to be integrated with a polyethylene glycol (PEG) reservoir prepared using several types of PEG with different molecular weights. The ex vivo permeation study showed that up to 80% of SC (equivalent to 20.2 ± 0.29 mg/mL) was delivered transdermally from this combined dosage form. For the first time, SC has been successfully developed into an HFM that was integrated with a PEG reservoir which was non-irritating, safe, and painless. It also had promising results for increasing the effectiveness of ED therapy.