Development of an Immediate-Release Prototype Tablet Formulation of Hydroxychloroquine Sulfate with an Interwoven Taste-Masking System.

Hydroxychloroquine sulfate (HCQS) was granted US-FDA approval in 1955 for the prevention and treatment of malaria. Since then, its uses have expanded to treat systemic lupus erythematosus and rheumatoid arthritis.  For each indication, HCQS is a crucial option for the treatment of pediatric, juvenile, adult, and elderly populations. Existing currently on the market are only 200-mg strength tablets exclusively for adult administration. To facilitate weight-based administration for pediatric and juvenile patients, an HCQS suspension is made by compounding a 200-mg HCQS tablet and suspending the crushed granules into water and Ora-Plus®. The Ora-Plus® suspension does not alter the extreme bitterness of HCQS such that it facilitates oral administration. Additional research has been executed to affirm that a slightly buffered, ion-pairing system, reduces the bitterness of HCQS. The buffered, ion-pairing system can be interwoven into an immediate-release tablet formulation likely without compromising tablet performance. With the taste-masking system embedded, the tablet could be more easily be compounded and suspended in water to generate a palatable oral suspension. Such a novel HCQS 200-mg tablet would be tailored for adult usages wherein the interwoven task-masking system could be utilized to facilitate weight-based administration for pediatric and juvenile patients. The dual quality target product profile of the tablet and the tablet compounded for suspension in water would make the tablet formulation applicable to a wide patient population ranging from pediatric to elder adults to facilitate in improving compliance and overall health outcomes.

Preparation and characterization of fast dissolving pullulan films containing BCS class II drug nanoparticles for bioavailability enhancement.

The aim of this study is to assess pullulan as a novel steric stabilizer during the wet-stirred media milling (WSMM) of griseofulvin, a model poorly water-soluble drug, and as a film-former in the preparation of strip films via casting-drying the wet-milled drug suspensions for dissolution and bioavailability enhancement. To this end, pullulan films, with xanthan gum (XG) as thickening agent and glycerin as plasticizer, were loaded with griseofulvin nanoparticles prepared by WSMM using pullulan in combination with sodium dodecyl sulfate (SDS) as an ionic stabilizer. The effects of drug loading and milling time on the particle size and suspension stability were investigated, as well as XG concentration and casting thickness on film properties and dissolution rate. The nanosuspensions prepared with pullulan-SDS combination were relatively stable over 7 days; hence, this combination was used for the film preparation. All pullulan-based strip films exhibited excellent content uniformity (most <3% RSD) despite containing only 0.3-1.3 mg drug, which was ensured by the use of precursor suspensions with >5000 cP viscosity. USP IV dissolution tests revealed fast/immediate drug release (t80 < 30 min) from films <120 µm thick. Thinner films, films with lower XG loading, or smaller drug particles led to faster drug dissolution, while drug loading had no discernible effect. Overall, these results suggest that pullulan may serve as an acceptable stabilizer for media milling in combination with surfactant as well as a fast-dissolving film former for the fast release of poorly water-soluble drug nanoparticles.