Under the Hood: Amorphous Solids

Part 1 in my Under the Hood series.


Amorphous solids.  Those of you who may be frequent readers of my blog in the future, this may be the single most important scientific post to understanding what my graduate research is all about.  Entire journals and books can be written about the amorphous state, but I will do my best to summarize and generalize as best I can.

Amorphous Solids lack the long range order of Crystalline solids,
which leads to greater molecular mobility.
(Taken from IPPH 587 notes)

This free energy diagram shows how the phases change with
respect to theromdynamics of the system.
Tm is the melting point, and Tg is the
glass transition temperature of the amorphous solid.
(Taken from IPPH 587 notes)

So, what is an amorphous solid?  I like to tell people it is the state between solid and liquid, however that is not exactly true.  It is between these two in the classical sense.  In grade school, a solid is anything that has long range order and a melting point (some even define a solid as anything that doesn’t take the shape of the container it is in).  Well, this is the definition of a crystalline solid.  The majority of “solids” are crystalline solids including metals, alloys, salts, etc.  Then there are amorphous solids.  These are essentially solids that lack the long range order of crystalline solids, but also lack the mobility of liquids.  For simplicity I will refer to all amorphous solids as the same thing but there are really two types of amorphous solids; those being glasses and super-cooled liquids. The diagram to the right shows a thermodynamic view of these states.  Overall, these are meta-stable states and need some kind of thermodynamic event or action to occur.  Nature prefers crystalline solids and liquids over amorphous forms.

BCS drug classifcation system.  Here, BCS is not some
money hungry way to exploit football, but actually a way
to classify drugs and allow biowaivers to expedite the drug
development process.

And why do we care about amorphous solids?  Let’s begin with drug development/discovery.  Here in the western hemisphere (and increasingly in the entire world) we prefer solid dosage forms compared to liquids or parenterals (injections).  They are more patient compliant and easier to market not to mention it is much easier to ask someone to take a pill twice a day rather than give them a shot or make them drink really, really nasty tasting liquids.  So we want pills, tablets, capsules, something solid to swallow.  There are many other reasons why these are preferred but this will have to suffice for this explanation. Now, the stomach and intestine need to be able to dissolve the drug and as you probably learned in 4^th grade, we are roughly 60% water.  Thus new drugs need to be water soluble.  Unfortunately new molecules which show some biological activity are not water soluble.  Depending on who you ask 60-80% of new drug molecules fall into this not water soluble category (Class II/IV drugs, see BCS chart).  Thus, we must come up with strategies to obtain higher solubility.  Here is where amorphous solids come in.  Since these solids have less order and are more unstable than their crystalline counterparts, they can obtain higher solubilities.  Sometimes 10-50 fold higher.  Thus we can use drugs in their amorphous form to utilize drug molecules that otherwise we have rendered useless.  Not to mention we can lower doses, lower prices, and increase efficacy on drugs already on the market.  I think everyone can agree those are all worthwhile. 

Studying the crystal growth rates from the amorphous
state is very critical to our research.  This is a crystal
growing from the amorphous state under cross-
polarizing light to determine crystallinity.

And where does my research fit in?  Well, these amorphous forms are unstable and want to convert to their non-soluble crystalline forms.  The research I am working on deals with understanding the kinetics and mechanisms behind stabilization of amorphous drugs.  Even though we can observe what happens, we want to be able to explain and even predict what will happen to drugs in the amorphous form.

I will leave you with an example and an explanation of one more common term.  First, most glass is amorphous.  If glass had a crystal lattice structure, light would refract through it like a prism and we couldn’t see through it clearly.  So the next time you are in a really old building or barn, check out the windows.  They may appear to be “collecting” at the bottom like they are liquids.  And finally, if you ever see the term amorphous solid dispersion (or ASD), it is when a drug or compound is “dispersed” with a polymer to create an amorphous state.  The polymer, which is inherently amorphous because of the repeating nature and large molecular size, acts to inhibit crystallization of the drug.  Using these ASD’s are common place in both research and pharmaceuticals and are the basis for most of the research on our lab. 

Well, there is a quick overview of amorphous solids.  If you have any questions just leave a comment or shoot me an email and I can try to answer, or point you toward a source that can hopefully explain in better.