One man and three women were held this morning as part of a huge investigation that was triggered by a whistle-blower last November.
They remain in custody.
It takes the number of medics arrested to seven, following the arrests of a female nurse in November and a male and female nurse in December. They were later released under investigation.
All seven suspects have been suspended; the three arrested last year since November, and the four arrested today since December.
Det Ch Jill Johnston, from Lancashire Police, said the force's complex investigation into "allegations of mistreatment and neglect of patients ... is very much on-going".
She said: "I understand further arrests could be concerning but I would like to reassure people we have a dedicated team of detectives working on this investigation.
“Our priority and the priority of the Blackpool Teaching Hospitals NHS Foundation Trust [which runs the hospital] is to ensure the safety of patients.
“Given the number of arrests and the nature of the allegations, it remains a complex and sensitive inquiry.
“No timescales have been set and I would ask people to remain patient while we continue to conduct our enquiries.
“A number of post-mortem examinations have taken place in connection with our investigation and we are supporting those families who have had loved ones identified as potentially being involved.
"They are being kept fully updated and supported throughout the process by specially trained officers.
“We are working closely with the trust as well as [the] coroner for Blackpool and Fylde as part of the investigation.”
The drug, Zopiclone, comes in pill or liquid form. It is widely used and, when used properly, is safe.
A number of funerals have been delayed to allow for post-mortem examinations to be carried out, families have said in recent months, though police have not said how many, if any, confirmed poisoning victims have been identified.
One of the post-mortems triggered a murder probe in January, with a suspicious injury being found on the body of Valerie Kneale, 75, who died on the stroke unit on November 16.
In a statement, Mrs Kneale's family said: "We ... are completely and utterly devastated and heartbroken to have lost Val in these circumstances.
“She was the most precious wife, mother and grandmother, our constant friend and problem solver who we will miss dearly."
Wendy Swift, the chief executive at the Vic, said: “We take all allegations of this type extremely seriously and when the concerns were raised last year about the individuals they were immediately suspended.
“The trust contacted police as soon the allegations were made, and we are continuing to work with them and co-operating fully with their investigation.
“We would like to reassure our patients that all necessary actions are being taken. The hospital remains a safe and caring environment for patients and the provision of services will continue as usual.’’