Design And Development of Sublingual Films Incorporating R-HCL And Vitamin D-Loaded NLCS

Osteoporosis, particularly postmenopausal (Type I), is a progressive bone disorder characterized by reduced bone density and increased fracture risk, primarily due to estrogen deficiency. Raloxifene Hydrochloride (R-HCl), a selective estrogen receptor modulator (SERM), offers bone-protective effects without adversely impacting the uterus or breast. However, its low solubility and poor oral bioavailability limit therapeutic effectiveness. This study aimed to enhance the solubility and permeability of R-HCl by formulating nanostructured lipid carriers (NLCs) co-loaded with Vitamin D (Vit D), a vital supplement in bone health, using the micro-emulsification technique followed by high-speed homogenization. The optimized NLCs demonstrated a mean particle size below 300 nm, a narrow polydispersity index (0.192), and a negative zeta potential (-0.69 mV), indicating uniformity and stability. Entrapment efficiency was observed at 91.41% for R-HCl and 79.56% for Vit D, with corresponding drug content values of 85.76% and 80.24%. Characterization by DSC and FTIR confirmed stable drug incorporation, while HRTEM revealed spherical morphology. These NLCs were incorporated into sublingual films prepared using HPMC and glycerol, offering improved bioavailability and bypassing first-pass metabolism. The films exhibited favorable organoleptic properties, rapid disintegration, high tensile strength (5.453 N/mm²), uniform weight, and surface pH of 6.8—comparable to buccal pH—ensuring mucosal compatibility. Drug content per cm² was 89.43% (R-HCl) and 84.67% (Vit D), with efficient in vitro drug release. This study highlights the successful development of R-HCl and Vit D-loaded NLCs in film form as a promising and effective approach for managing postmenopausal osteoporosis.