3D-Printed Capsaicin-Loaded Injectable Implants for Targeted Delivery in Obese Patients.

Diet-induced obesity and hyperlipidemia are a growing public health concern leading to various metabolic disorders. Capsaicin, a major bioactive compound obtained from natural chili peppers, has demonstrated its numerous beneficial roles in treating obesity and weight loss. Current treatment involves either administration of antiobesity drugs or surgical procedures such as Roux-en-Y-gastric bypass or sleeve gastrectomy, both of which are associated with serious side effects and poor patient acceptance. Capsaicin, a pungent molecule, has low oral bioavailability. Therefore, there is a need for the development of site-specific drug delivery system for capsaicin. The present study is aimed at preparing and characterizing 3D-printed capsaicin-loaded rod-shaped implants by thermoplastic extrusion-based 3D printing technology. The implants were printed with capsaicin-loaded into a biodegradable polymer, polycaprolactone, at different drug loadings and infill densities. The surface morphology revealed a smooth and uniform external surface without any capsaicin crystals. DSC thermograms showed no significant changes/exothermic events among the blends suggesting no drug polymer interactions. The in vitro release studies showed a biphasic release profile for capsaicin, and the release was sustained for more than three months (~ 85% released) irrespective of drug loading and infill densities. The HPLC method was stability-indicating and showed good resolution for its analogs, dihydrocapsaicin and nordihydrocapsaicin. The implants were stable for three months at accelerated conditions (40°C) without any significant decrease in the assay of capsaicin. Therefore, capsaicin-loaded implants can serve as a long-acting injectable formulation for targeting the adipose tissue region in obese patients.

Inclusion Complex of Clomiphene Citrate with Hydroxypropyl-ß-Cyclodextrin for Intravenous Injection: Formulation and Stability Studies.

Clomiphene citrate is the first-line treatment for women with abnormal or failed ovulation. Currently, it is available as oral tablets, and the parenteral formulation does not exist. In this study, we prepared clomiphene citrate-hydroxypropyl-ß-cyclodextrin inclusion complex for its use in intravenous injection. The inclusion complex was characterized in the liquid state (phase solubility) and solid state by differential scanning calorimetry, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy analyses. The sterile intravenous injection containing 0.5% clomiphene citrate was prepared and characterized for its physical properties, assay, pH, and osmolality. A stability-indicating high-performance liquid chromatography (HPLC) method for the injection was developed. The HPLC method was validated for the assay, linearity, precision and repeatability, benchtop stability, and forced degradation to elute clomiphene isomers from the degradation products. The injection was packed in sterile 10-ml glass vials with butyl rubber stoppers and stored at 40°C, room temperature, and 4°C. The samples at 0, 0.5, 1, 2, 3, and 6 months were analyzed for clarity, pH, osmolality, and drug assay. The HPLC method was linear (R2 = 0.9999), precise (0.86% relative standard deviation), and stability indicating. The stability data at the accelerated (40°C) storage condition for 6 months showed satisfactory results: the drug assay in the injection was between 90 and 105%, the injection remained clear, pH was between 4.0 and 4.4, and osmolality was between 270 and 350 mOsm. The stability data suggests that the product is stable and meets the given analytical specifications.

Modification of O-ring intrauterine devices (IUDs) in mares: Contraception without estrus suppression.

A significant welfare concern for those within the horse industry is that of the overpopulation in free-roaming horses in the western US. The goal of the present study was to identify a humane and inexpensive means of providing contraception and reducing pregnancy rates in a way that could be applied to free-roaming horses on the western U.S. open range lands. A series of studies was conducted utilizing the previously-described silastic O-ring intrauterine devices (IUDs). Throughout these studies pregnancy was successfully prevented in mares with an O-ring IUD, but collective retention rates failed to exceed 50% regardless of size or durometer (material hardness/malleability). When the O-ring IUDs were compared to the recently-described Y-design IUDs (Holyoak et al., 2021) the Y-design IUDs had a markedly greater rate of retention; therefore, the Y-design IUDs would be most appropriate for potential use in free-roaming horses. Assessment of mare records revealed that the vast majority of mares continued to have ovulations and mating continued to occur while the IUDs were in place. A few mares had multiple small ovarian follicles when the IUD was in utero. Findings indicate that utilizing an IUD with the expectation of estrus suppression in mares would fail to be fruitful.