It sounds like you have a web browser (Internet Explorerer?) in a thinapp and you're trying to open PDF files using a natively installed Adobe Reader. I just went through the same thing. From what I experienced with an IE8 thinapp, Adobe Reader 10 and 11 both get fussy about running while in the thinapp bubble.
The best solution I could find was to add the line below to package.ini
ChildProcessEnvironmentExceptions=AcroRd32.exe;winword.exe;excel.exe;outlook.exe
In my case, users needed to open .docx, .xlsx, .pdf and use "send to email" functions, so I excluded all of the associated applications from running in the default virtual environment.
Because the processes are now running outside of the virtual bubble, you also need to set isolation on the %Internet Cache% directory in your package files to "merged" by editing the ##Attributes.ini file. The downside to this is that the IE temp files from the thinapp are now mingling with the native temp files but so far I haven't had issues with it. To help mitigate the problem, I've got the "Delete Browsing History on Exit" setting enabled in the virtual IE.
