Incorporation of Inclusion Complexes in the Dissolvable Microneedle Ocular Patch System for the Efficiency of Fluconazole in the Therapy of Fungal Keratitis.

Fluconazole (FNL) is one of the first-line treatments for fungal keratitis as it is an effective broad-spectrum antimicrobial commonly administered orally or topically. However, FNL has a very low water solubility, limiting its drug formulation, therapeutic application, and bioavailability through tissues. To overcome these limitations, this study aimed to develop FNL inclusion complexes (FNL-IC) with cyclodextrin (α-cyclodextrin, sulfobutylether-ß-cyclodextrin, and hydroxypropyl-γ cyclodextrin) and incorporate it into a dissolvable microneedle (DMN) system to improve solubility and drug penetration. FNL-IC was evaluated for saturation solubility, Fourier transform infrared spectroscopy, differential scanning calorimetry, in vitro release, minimum inhibitory concentration, minimum fungicidal concentration, and time-killing assay. DMN-FNL-IC was evaluated for mechanical and insertion properties, surface pH, moisture absorption ability, water vapor transmission, and drug content recovery. Moreover, ocular kinetic, ex vivo antimicrobial, in vivo antifungal, and chorioallantoic membrane (HET-CAM) assays were conducted to assess the overall performance of the formulation. Mechanical strength and insertion properties revealed that DMN-FNL-IC has great mechanical and insertion properties. The in vitro release of FNL-IC was significantly improved, exhibiting a 9-fold increase compared to pure FNL. The ex vivo antifungal activity showed significant inhibition of Candida albicans from 6.54 to 0.73 log cfu/mL or 100-0.94%. In vivo numbers of colonies of 0.87 ± 0.13 log cfu/mL (F2), 4.76 ± 0.26 log cfu/mL (FNL eye drops), 3.89 ± 0.24 log cfu/mL (FNL ointments), and 8.04 ± 0.58 log cfu/mL (control) showed the effectiveness of DMN preparations against other standard commercial preparations. The HET-CAM assay showed that DMN-FNL-IC (F2) did not show any vascular damage. Finally, a combination of FNL-IC and DMN was developed appropriately for ocular delivery of FNL, which was safe and increased the effectiveness of treatments for fungal keratitis.

Polymeric hydrogel forming microneedle-mediated transdermal delivery of sildenafil citrate from direct-compressed tablet reservoir for potential improvement of pulmonary hypertension therapy.

Pulmonary hypertension (PH) is a cardiovascular disease affecting patient's life. Sildenafil citrate (SC), the first-line treatment, is present in oral and injectable forms with some drawbacks, primarily poor patient's comfort and low oral bioavailability. To counter these limitations, stratum corneum-penetrating hydrogel-forming microneedles (HFM) was created, making it easier to distribute SC transdermally. HFM was fabricated using polyvinyl alcohol (PVA) and two variations of polyvinyl pyrrolidone's (PVP) concentration as polymers and citric acid (CA) as crosslinking agent. The crosslinking time was also variated. The assessment of swelling, insertion characteristics, and mechanical resistance revealed that it possessed swelling capacities up to 470 % and strong insertion capabilities. This HFM was integrated with a tablet reservoir prepared using several concentrations of sodium starch glycolate (SSG) as super disintegrant. The tablet reservoir's hardness, dissolution rate, XRD, and FTIR profiles were evaluated and the results showed that 4 % of SSG was the option for enhancing SC's solubility. According to ex vivo study, this system released 24.12 ± 0.92 % of SC. For the first time, SC was successfully incorporated into a system of HFM and tablet reservoir and was non-toxic, showing promise in terms of improving PAH therapy's efficacy following comprehensive in vivo studies in the future.