Purpose: Solid dispersion is a key technology to address solubility/dissolution issues of water-insoluble compounds, which continue to be one of the major challenges facing the pharmaceutical industry in terms of oral drug delivery. Up to 90% of current candidates from the discovery small molecule pipelines, across many therapeutic areas, are having solubility/dissolution problems. Multiple dispersion techniques have been developed in the past. The purpose of this poster is to provide an industrial assessment of different dispersion techniques through public literatures.
Methods: The term “solid dispersion” is defined as a dispersion of drugs in a matrix in solid state, prepared by melting (fusion), solvent, or melting-solvent methods (Chiou, 1971), as well as other non-traditional technique, such as co-grinding (Kaneniwa, 1975). Solid dispersions can be generally grouped into the following categories - eutectic-mixtures, solid-solutions, crystalline-suspensions, glass-solutions, and glass-suspensions.
The characteristics and performance of these dispersions are assessed based upon the criteria of active pharmaceutical ingredient crystallinity, drug loading, dissolution performance, stability and excipient compatibility.
Results: For the eutectic-mixture, solid-solution and crystalline-suspension APIs exist in crystalline solid state. The eutectic-mixtures, solid-solutions and crystalline-suspensions are therefore considered crystalline-based solid dispersions. For glass-solution and glass-suspension APIs exist in an amorphous solid state. Glass-solutions and glass-suspensions are therefore considered amorphous-based solid dispersions (Leuner 2000, Craig 2002, Singh 2011).
Among these solid dispersions, crystalline-based solid dispersions possess better stability but inferior dissolution performance compared to amorphous-based solid dispersions (Brough, 2013).
For crystalline-suspensions, drug or API loading in a pharmaceutical composition can be greater than 50% wt/wt. However, achieving such high drug loading requires that API particles be within nano/micro particle size range in the crystalline-suspension (Kawabata 2011). For eutectic-mixtures, the drug loading is typically no more than 50% wt/wt without specific control of API particle size (Law 2003, Cherukuvada 2014).
Amorphous-based solid dispersions generally possess better dissolution performance due to the amorphous nature of the API. However, due to the amorphous nature of the API, amorphous-based solid dispersions have a higher degree of instability. Consequently, drug loading of such dispersions is generally no more than 50% wt/wt in order to reduce the risk of instability (Shah 2014, Newman 2015).
Both crystalline-based and amorphous-based solid dispersions possess better drug-drug and drug-excipient compatibility than the conventional dry-blended drugs (Nie, 2017).
Conclusion: This assessment provides a quick clear criteria and guidance in selecting the suitable solid dispersion techniques for optimum design of drug products.
Hsien-Hsin Tung– AcrysPharm, LLC., Scotch Plains