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

Abstract

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 filmforming 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.

Rizatriptan-Loaded Oral Fast Dissolving Films: Design and Characterizations

“…The positive sign specifies that as the level of MTX and PG increased, the moisture absorption (%) of RZT-ODFs substantially increased. Equation (12) shows that the influence of X 2 on the response (Y 6 ) was more substantial (p < 0.05) than X 3 .…”

“…Equation (12) showed that PUL amount (X1) suggested a negative influence, while MTX amount (X2) and PG amount (X3) had a synergistic impact on the response Y6. It was noted that slight increases in PUL amount significantly decreased moisture uptake (%).…”

“…Therefore, a thorough study must be undertaken to optimize the formulation parameters of ODFs using experimental design. A variety of hydrophilic synthetic and natural polymers were used as a film forming materials, such as hydroxyl-propyl methyl-cellulose (HPMC) [12], pullulan (PUL) [13], maltodextrin (MLT) [14], Kollicoat ® IR [15], cyclodextrins, polyvinyl alcohol (PVA) [1], polyvinyl-pyrrolidone (PVP) [10], and many others.…”

Orthogonal Gelations to Synthesize Core–Shell Hydrogels Loaded with Nanoemulsion‐Templated Drug Nanoparticles for Versatile Oral Drug Delivery

“…Most notably, the incorporation of API-loaded hydrophobic nanodomains (including micelles, nanoemulsions, and lipid nanoparticles) into the hydrogel matrix has allowed for the development of high drug-loaded hydrogel formulations of hydrophobic APIs. [21][22][23][24][25][26][27][28][29][30][31] These hydrophobic nanodomains impart control over the formation of API nanoparticles in the polymeric matrix. This approach exploits the benefits of crystal size reduction from the bottom-up, avoiding the limitations of milling and ASDs.…”

“…We selected biocompatible and naturally-derived model polymers to demonstrate this approach: methylcellulose (MC) as the thermogelling polymer and alginate as the inotropic model gelator. MC has long been used as an excipient in pharmaceutical and food formulations because of its reversible thermal sol-gel behavior, [56][57][58][59] controllable erosion, [26,27,60,61] and tensioactive capabilities. [62][63][64] Alginate is also an ideal excipient for controlled delivery, [30,[65][66][67] where its anionic property can protect therapeutics from being released in the gastric environment, [68][69][70][71] making alginate an optimal enteric coating.…”