Ok let's look at the two components to firearms reliability - the ammunition and the firearm itself. Let's start with the ammunition:
Probably like many here I've shot probably over 100,000 rounds of .22LR to date across a number of platforms in both pistols and rifles. Basically, as you decrease the cost of the ammunition, you decrease the reliability of each round going bang. As you get into a better quality ammunition - say CCI Velocitor (one of my favorites, very high velocity and 40 grains) the reliability of the ammunition improves significantly. Side by side probably not quite to centerfire standards, but very close. There are others - Aguila Interceptor is the CCI Velocitor twin from foriegn soil is another I think is very good. I prefer the heavier rounds and solid noses in general. You are probably paying twice what you would for bulk ammo, but that still is only $6 per 50 or so.
Now, as an alternative - .22 WMR is much more reliable still and packs more energy than the .22LR in 40 grains, by about 50% or so. Still is very low recoil even in small platforms.
So, let's switch to platforms for a minute. If I were looking to carry as a .22LR in a semi - auto, the lowest price gun I would probably consider would be the Bersa Thunder .22LR - and only because I have now spent some time behind my dad's pistol which started out as a range gun and is proving to be something more. In general I would look at guns which are built for larger calibers and then chambered in .22LR rather than guns that are on the cheaper side. Along this same vein, the gun I would recommend. (and have spent some time behind as well) is the Beretta 87. (Not the 87T which is the target model) It's expensive - in fact, about the same cost as the Beretta 84 in .380 ... because it is the same gun, just chambered in .22LR. It is substantially more reliable than something like the P22. $800 for one only sounds like a lot of money when you are running the plastic, once you sign the receipt it's just another number. I've heard a few good things about the new Walther PPK/S in .22LR, but I've not even held one much less shot one.
The other way to mitigate is to look at a revolver. There are some excellent quality compact revolvers in both .22LR and .22WMR as well as some options that are set up as combos. In fact, most of the revolver manufacturers make some version of a centerfire revolver in .22LR. Ruger makes a version of their excellent SP101 in .22LR, I have a Smith and Wesson 317 AirWeight Kit Gun with Hi - Viz sights which is 8 shots and an excellent option. the 351PD in .22 WMR at 7 shots with Hi Viz sights is also a great revolver. The revolver also mitigates some of the reliability risk of the ammo - because if the round doesn't fire, just keep pulling the trigger - you'll get the next one.
Again, not cheap - but think of it this way - you are paying for a centerfire quality firearm and all that describes. It just happens to be chambered as a .22. However, your application is the same as if it were centerfire, it's just you can't get there from here.
I would definitely not get a 25 ACP. The choices of handguns in that caliber are very poor - probably the Taurus or Beretta Bobcat style guns are the most common, and they do not have extractors as part of their design which means they are MORE sensitive to limp wristing as a mode of failure. Given the problem your wife has at the moment, that makes her more likely to have that problem.
Thinkingblade