The prevalence of female reproductive system disorders is increasing, especially among women of reproductive age, significantly impacting their quality of life and overall health. Managing these diseases effectively is challenging due to the complex nature of the female reproductive system, characterized by dynamic physiological environments and intricate anatomical structures. Innovative drug delivery approaches are necessary to facilitate the precise regulation and manipulation of biological tissues. Nanotechnology is increasingly considered to manage reproductive system disorders, for example, nanomaterial imaging allows for early detection and enhances diagnostic precision to determine disease severity and progression. Additionally, nano drug delivery systems are gaining attention for their ability to target the reproductive system successfully, thereby increasing therapeutic efficacy and decreasing side effects. This comprehensive review outlines the anatomy of the female upper genital tract by highlighting the complex mucosal barriers and their impact on systemic and local drug delivery. Advances in nano drug delivery are described for their sustainable therapeutic action and increased biocompatibility to highlight the potential of nano drug delivery strategies in managing female upper genital tract disorders.

Background/Objectives: Ivermectin gained widespread attention as the “miracle drug” during the coronavirus disease 2019 (COVID-19) pandemic. Its inclusion in the 21st World Health Organization (WHO) List of Essential Medicines is attributed to its targeted anti-helminthic response, high efficacy, cost-effectiveness and favorable safety profile. Since the late 2000s, this bio-inspired active pharmaceutical ingredient (API) gained renewed interest for its diverse therapeutic capabilities. However, producing ivermectin formulations does remain challenging due to its poor water solubility, resulting in low bioavailability after oral administration. Therefore, the transdermal drug delivery of ivermectin was considered to overcome these challenges, which are observed after oral administration. Methods: Ivermectin was incorporated in a nano-emulsion, nano-emulgel and a colloidal suspension as ivermectin-loaded nanoparticles. The nano-drug delivery vehicles were optimized, characterized and evaluated through in vitro membrane release studies, ex vivo skin diffusion studies and tape-stripping to determine whether ivermectin was successfully released from its vehicle and delivered transdermally and/or topically throughout the skin. This study concluded with cytotoxicity tests using the methyl thiazolyl tetrazolium (MTT) and neutral red (NR) assays on both human immortalized epidermal keratinocytes (HaCaT) and human immortalized dermal fibroblasts (BJ-5ta). Results: Ivermectin was successfully released from each vehicle, delivered transdermally and topically throughout the skin and demonstrated little to no cytotoxicity at concentrations that diffused through the skin. Conclusions: The type of nano-drug delivery vehicle used to incorporate ivermectin influences its delivery both topically and transdermally, highlighting the dynamic equilibrium between the vehicle, the API and the skin.

Despite being discovered over five decades ago, little is still known about ivermectin. Ivermectin has several physico-chemical properties that can result in it having poor bioavailability. In this study, polymorphic and co-crystal screening was used to see if such solid-state modifications can improve the oil solubility of ivermectin. Span® 60, a lipophilic non-ionic surfactant, was chosen as co-former. The rationale behind attempting to improve oil solubility was to use ivermectin in future topical and transdermal preparations to treat a range of skin conditions like scabies and head lice. Physical mixtures were also prepared in the same molar ratios as the co-crystal candidates, to serve as controls. Solid-state characterization was performed using X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The FTIR spectra of the co-crystal candidates showed the presence of Span® 60’s alkyl chain peaks, which were absent in the spectra of the physical mixtures. Due to the absence of single-crystal X-ray data, co-crystal formation could not be confirmed, and therefore these co-crystal candidates were referred to as co-processed crystalline solids. Following characterization, the solid-state forms, physical mixtures and ivermectin raw material were dissolved in natural penetration enhancers, i.e., avocado oil (AVO) and evening primrose oil (EPO). The co-processed solids showed increased oil solubility by up to 169% compared to ivermectin raw material. The results suggest that co-processing of ivermectin with Span® 60 can be used to increase its oil solubility and can be useful in the development of oil-based drug formulations.

The treatment of parasitic infections has evolved in terms of effectiveness and the prevention of drug resistance. This is highlighted by the discovery of ivermectin (IVM), a macrocyclic lactone and broad-spectrum antiparasitic agent. IVM garnered scientific attention by presenting a therapeutic alternative in the field of veterinary medicine due to its control of multiple parasite species, including nematodes and soil-transmitted helminths. Shortly after its discovery, IVM was approved for human use by the World Health Organization (WHO) and United States Food and Drug Administration (FDA) for combating head lice, onchocerciasis, rosacea, scabies, and worm infestations within the gastrointestinal tract (GIT). In veterinary medicine, IVM is available in a range of formulations and can be administered via different routes (i.e., oral, topical, and parenteral), whereas for humans, IVM is only approved as a single oral dose and dermal cream. Establishing a comprehensive overview of IVM’s applications in both human and veterinary medicine is necessary, particularly in light of its repurposing potential as a treatment for various conditions and emerging diseases. Given its primary application in veterinary medicine, there is a need to enhance the development of dosage forms suitable for human use. Therefore, this review details the discovery, mechanisms, and applications of IVM, while also examining the challenges of resistance, side-effects, and controversy surrounding its use, to ultimately emphasize the importance of targeted, optimized IVM delivery via tailored dosage form development in animals and humans as part of the One Health approach to interlink innovations across veterinary and human medicine fields.

In this work, we present the preparation and evaluation of previously unreported metastable forms of the antiretroviral drug, lopinavir. By maintaining the chemical structure, physicochemical properties like the glass transition temperature (Tg ), dissolution and solubility can be readily attributed to the stability of the system. Commercially-available lopinavir was used to prepare partially amorphous crystals, semicrystalline needles, resins and glasses. The physicochemical properties of each were investigated using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (PXRD). Each sample's thermal and spectroscopic analyses, as well as dissolution and solubility studies were performed one month after sample preparation, for better comparability. Glass transition temperature, activation energy for global molecular mobility (ΔETg ), and activation energy for local molecular mobility (ΔEβ ) were assessed as primary indicators for structural stability of the systems. Relating these properties to aqueous solubility revealed that each metastable form possessed its own unique equilibrium solubility. Cumulative dissolved fractions (α) were fitted against deceleratory kinetics models, and from the data hereby obtained the dissolution process was determined to followed first-order kinetics (R2 = 0.998). From the rate constants, the activation energy for dissolution (ΔEDiss ) of each sample was calculated. The results suggest that multiple metastable solid-state forms of lopinavir can exist under similar conditions, depending on the preparation conditions.

The crystallization of small-molecule drugs plays an important role in the pharmaceutical industry. Since many downstream industrial processes are heavily influenced by the crystalline properties of a drug, that is, crystal shape, size distribution, and polymorphic form, control over the crystallization process can facilitate manufacturing and testing. However, before the crystallization process can be controlled, an understanding of its underlying mechanisms is required. In this chapter, we will look at the thermodynamic driving force behind crystallization and how crystal nucleation and growth rates can be used to control the properties of the resulting crystals. Throughout the chapter, we give examples of how these control approaches can be applied in pharmaceutical research and industry to obtain crystals with desired properties. We then finish this chapter with a look at crystallization from the amorphous state, which differs from crystallization from solution and is a relevant topic in pharmaceutical sciences, since the preparation of an amorphous solid is a popular approach to enhancing the solubility of a drug.