Sildenafil citrate is a drug used throughout the world primarily to treat erectile dysfunction. Several problems with the commercially available product decrease its efficacy, such as limited solubility, delayed onset of action, and low bioavailability with a large variability in the absorption profile. This study aimed to develop an optimized self-nanoemulsifying lyophilized tablet for the drug to conquer the foresaid problems. Sildenafil solubility in various surfactants, oils, and cosurfactants was attempted. An optimized formulation of a loaded self-nanoemulsion with a small droplet size was developed by applying a special cubic model of the mixture design. Sixteen formulations were prepared and characterized for droplet size. On the basis of solubility studies, a clove oil/oleic acid mixture, polysorbate 20 (Tween 20), and propylene glycol were selected as the proposed oil, surfactant, and cosurfactant, respectively. On the basis of desirability, an optimized sildenafil citrate-loaded self-nanoemulsifying delivery system containing 10% of the oil mixture, 60% of the surfactant, and 30% of the cosurfactant had a droplet size of 65 nm. Subsequently, the tablet form was fabricated with optimum ratios of 0.4% fumed silica, 0.1% hydroxypropyl methylcellulose, and 0.4% sodium starch glycolate. This formula showed satisfactory results in both disintegration and dissolution studies. In vivo pharmacokinetic studies indicated a higher bioavailability (1.44 times) and rapid absorption profile for the study’s tablets compared with commercially available tablets. In conclusion, highly bioavailable oral lyophilized flash tablets of sildenafil were successfully prepared. They will be a good alternative to the conventional solid-dosage form.

Alopecia areata is a scarless, localized hair loss disorder that is typically treated with topical formulations that ultimately only further irritate the condition. Hence, the goal of this study was to develop a nanoemulsion with a base of garlic oil (GO) and apple cider vinegar (APCV) and loaded with minoxidil (MX) in order to enhance drug solubilization and permeation through skin. A distance coordinate exchange quadratic mixture design was used to optimize the proposed nanoemulsion. Span 20 and Tween 20 mixtures were used as the surfactant, and Transcutol was used as the co-surfactant. The developed formulations were characterized for their droplet size, minoxidil steady-state flux (MX Jss) and minimum inhibitory concentration (MIC) against Propionibacterium acnes. The optimized MX-GO-APCV nanoemulsion had a droplet size of 110 nm, MX Jss of 3 μg/cm2 h, and MIC of 0.275 μg/mL. The optimized formulation acquired the highest ex vivo skin permeation parameters compared to MX aqueous dispersion, and varying formulations lacked one or more components of the proposed nanoemulsion. GO and APCV in the optimized formulation had a synergistic, enhancing activity on the MX permeation across the skin membrane, and the percent permeated increased from 12.7% to 41.6%. Finally, the MX-GO-APCV nanoemulsion followed the Korsmeyer–Peppas model of diffusion, and the value of the release exponent (n) obtained for the formulations was found to be 1.0124, implying that the MX permeation followed Super case II transport. These results demonstrate that the MX-GO-APCV nanoemulsion formulation could be useful in promoting MX activity in treating alopecia areata.

Alopecia areata is a skin disorder characterized by scarless, localized hair loss that is usually managed by topical treatments that might further worsen the condition. Therefore, the current study aimed to develop nano-cubosomes loaded with finasteride (FI) and oregano oil (Or) to improve drug solubility and permeation through skin and then incorporate it into an aloe ferox gel base. An l-optimal coordinate exchange design was adopted to optimize nano-cubosomes. Phytantriol and Alkyl Acrylate were employed as the lipid material, and surfactant respectively for cubosomes manufacture. The produced formulations were assessed for their particle size, entrapment efficiency (EE%), FI steady-state flux (Jss) and minimum inhibitory concentration (MIC) against Pro-pionibacterium acnes. Optimal FI-Or-NCu had a particle size of 135 nm, EE% equals 70%, Jss of 1.85 μg/cm2.h, and MIC of 0.44 μg/ml. The optimum formulation loaded gel gained the highest drug release percent and ex vivo skin permeation compared to FI aqueous suspension, and pure FI loaded gel. Aloe ferox and oregano oil in the optimized gel formulation had a synergistic activity on the FI permeation across the skin and against the growth of p. acne bacteria which could favor their use in treating alopecia. Thus, this investigation affirms the ability of FI-Or-NCu loaded aloe ferox gel could be an effective strategy that would enhance FI release and permeation through skin and maximize its favorable effects in treating alopecia.