A recent US Pharmacopeia survey of formulation scientists highlighted that ~80% of respondents suffered project delays while ~30% experienced project termination due to limited compatibility with, or the ineffectiveness of, current solubility enhancing technologies. One driver for these statistics is that the current excipients used for solubility enhancement (e.g., HPMCAS) have limited applicability, and are unable to adapt their properties to their environment. Specifically, the physical properties of current excipients are static and limit the range of physicochemical properties of a drug substance that can be stabilized in both the high energy conditions of solubility enhancing processing techniques (e.g., hot melt extrusion, spray dried dispersion), and also the aqueous environment of the gastrointestinal tract (GIT). Here we will discuss DPODs, an environmentally-responsive cross-linked polymer, which adapts to the significantly different environments of drug product manufacturing and the GIT in order to yield a shelf-stable oral solid dosage form with high drug loading while also achieving and stabilizing a supersaturated solution.
DPODs are composed of an inert polymer matrix capable of (1) loading with drug substance, which transforms into nanocrystals imparting excellent physical stability, and fast dissolution, and (2) spontaneous dissociation into solubility-enhancing polymers after oral delivery, to achieve and sustain supersaturation. Examples will be provided demonstrating that DPODs have proven effective in in-vitro dissolution studies, yielding drug concentrations over 1000 times the intrinsic solubility within 30 minutes and stabilized for hours from formulations with drug loading between 20% and 60%, with dozens of compounds spanning a broad range of physicochemical properties. Data will also be provided demonstrating the in-vivo bioavailability enhancement of a model drug.
Learning Objectives:
Summarize the challenges and limitations of current solubility-enhancing excipients.
Describe the unique properties and capabilities of the DPOD technology.
Understand examples of DPOD performance with clinically relevant drug substances.