New Cellulosic Excipients for Solubilization Of Active Pharmaceutical Ingredients

Over the past decade, an increasing percentage of the new chemical entities (NCEs) in pharmaceutical company pipelines have had poor oral bioavailability due to low aqueous solubility [1, 2]. This trend is largely due to recent biological targets, which tend to have higher lipophilicities and more diffuse binding sites.  Amorphous dispersions have proven to be a particularly successful drug-delivery approach for these compounds that have show poor bioavailability due low aqueous solubility. Amorphous dispersions can be made by spray-drying [1, 3], hot-melt extrusion [4], or precipitation [5].

Numerous polymers have been used as concentration-enhancing excipients in amorphous dispersions to improve oral solubilization. Among these dispersion polymers, hydroxypropyl methylcellulose acetate succinate (HPMCAS) has demonstrated superior solubilization performance both in vitro and in vivo.  HPMCAS polymers have demonstrated particular utility in spray-dried dispersions (SDDs) due to their high glass-transition temperatures (Tgs) and applicability across a broad range of active pharmaceutical ingredient (API) chemistries. HPMCAS SDDs exhibit excellent manufacturability, performance, and stability, and are readily incorporated into standard solid dosage forms, particularly tablets.

Although the U.S. Pharmacopeia (USP) specifications for HPMCAS are quite broad with respect to succinoyl and acetyl content, only a small portion of the acceptable space is covered by the traditionally available HPMCAS grades. Moreover, the traditionally available compositions tend to occupy only a small fraction of the -L, -M, and -H specification space. Thus, the actual chemical compositions of HPMCAS that have been available have been quite limited.

The goal of this work to demonstrate the potential utility of exploring a broad space of HPMCAS succinoyl and acetyl contents to maximize solubilization performance and bioavailability of specific active compounds.


This poster was presenting at the 2014 PBP World Meeting.

Bioavailability Enhancement