Since it is a command line tool, you can automate the process very easily.
PyPhisher.py --server mail.server.com --port 25 --username user --password password --html phish.txt --url_replace phishlink.com --subject Read!! --sender email@example.com --sendto firstname.lastname@example.org
In the above example, you can see that you need to populate the name of the email server and SMTP port as well as the credentials of an account that can send an email. You must also provide the path to the pre-crafted HTML file that you created. The URL replace argument allows you to choose the URL to the replace all links in the email with. With the sender argument, you can specify any sender however some email clients will flag this.