Thermogelling Hydroxypropyl Methylcellulose Nanoemulsions as Templates to Formulate Poorly Water-Soluble Drugs into Oral Thin Films Containing Drug Nanoparticles

摘要

Oral thin films are an emerging solid dosage form for the delivery of poorly water-soluble drugs. Typical thin film formulations require nanomilling of drugs to improve their poor water solubility, followed by incorporating the drug nanoparticles in a polymer solution for casting. However, these formulations are not only inefficient and multistep but also limited to moderate drug loading capacity and susceptible to irreversible nanoparticle aggregation. Based on a widely used film-forming polymer, hydroxypropyl methylcellulose (HPMC), we developed thermogelling nanoemulsions with drug-loaded oil nanodroplets dispersed in a HPMC-loaded water phase. The nanoemulsions can directly act as film precursors for casting and provide robust templates to formulate oral films with uniform drug nanoparticles embedded in a dried HPMC matrix. The thermally gelled network effectively immobilizes the oil nanodroplets for confined nanoparticle crystallization and avoids potential irreversible nanoparticle aggregation, which enables high drug loading contents up to 63 wt . The oral films also possess a tunable immediate release because the films have large surface-to-volume ratios and the drug nanoparticles are fast-dissolving. Overall, the thermogelling nanoemulsions show great promise for a more efficient and effective process to formulate HPMC and poorly water-soluble drugs into highly potent oral films with tunable immediate release.