X3 - Crackling on certain Kontakt 5 instruments stops when I reload the instrument preset?

The dropouts are most likely due to I/O, not CPU. If you're like most users, you've got all your libraries on one drive, so Kontakt's having to stream data for multiple instruments from the same physical device. At some point, you can eventually exhaust the bandwidth of the drive and controller.
 
There are a couple of stopgap measures you can take. One is to purge the largest instruments' sample buffers, which will free up RAM. Click on the "Purge" dropdown menu in the instrument header and choose "update sample pool". Note that the memory usage drops, often by a great deal - large libraries with many articulations, round-robins and velocity layers can drop by 90%. You have to do this after you've played your project once all the way through.
 
Another thing is to adjust the preload buffer size. This is set by the developer, and the default is usually fine for single instruments but may need to be increased when you have many instruments. Click on the wrench icon, and then the Instrument Options button, then click the DFD tab. There you will find the DFD preload buffer size slilder. Increasing the preload buffer will lessen the load on your disk drive at the expense of RAM.
 
Some instruments offer one other trick for reducing both memory usage and streaming bandwidth, and that is to reduce the number of round-robins. My favorite bass library is a monster - over a GB of RAM used when fully loaded. But it lets you choose how many round-robins to use. Reducing them to 4 from the default of 32 (which is serious overkill for a bass) cuts memory usage in half.
 
String libraries are especially notorious for using memory unnecessarily. When using Multis, make sure you're only loading the articulations you're actually going to use. If your piece has no need for pizzicato, don't load it.
 
 
Afterthought: it's possible your I/O problems aren't entirely attributable to Kontakt. It may be competing with some other process for bandwidth. For example, you may be using the same drive for paging or Windows event logging. Or you could have a piece of hardware that's hogging the CPU, such as a high-end gaming video card or a network adapter.  It's probably a good idea to check your DPC latency, if only to eliminate that possibility.