There are a variety of different ways that you could go about securing a script. All have pluses and minuses, and its likely that the correct answer for your situation will be a combination of several.
Like mentioned, you could lock down the account with Apache...it's a good start. Similarly, you could build a powerful 'salt-ed' security system such as this: http://www.devarticles.com/c/a/JavaScript/Building-a-CHAP-Login-System-An-ObjectOriented-Approach/ If you use SSL as well, you're essentially getting yourself security like banks use on their websites--not perfect, but certainly not easy to break into.
But there are other ideas to consider too. Park your script in a class file that sits inaccessible via direct URI, then do calls to the various functions from an intermediary view script. Not perfect, but it does limit the ways that someone could directly access the file. Consider adding a "qualifier" to the URL via a simple get--have the script check for the qualifier or fail....again, not a great solution on its own, but one additional layer to dissuade the bad guys. If you have control of who's getting access (know exactly which networks) you could even go so far as to limit the IP's or the http referers that are allowed to access the file. Consider setting and checking cookies, with a clear expiration. Don't forget to set your robots file so the browsers don't stumble upon the script your trying to protect.
A while back my company did a membership app using Delphi on the front end, talking to php and MySql on the backend....it was a bit clunky given that we were all web application developers. If you're so inclined, perhaps Adobe Flex might be an option. But ultimately, you'll have to open a door that the application could talk to, and if someone was determined, theoretically they could dig through your app to find the credentials and use them to gain instant access to the site. If you're going the desktop app route, perhaps its time to consider having the app avoid talking to an intermediary script and do its work on the local machine, communicating the db that sits remote.