WEST PALM BEACH, Fla. — Florida has long been the nation’s center of the illegal sale of prescription drugs: Doctors here bought 89 percent of all the Oxycodone sold in the country last year. At its peak, so many out-of-staters flocked to Florida to buy drugs at more than 1,000 pain clinics that the state earned the nickname “Oxy Express.”

But with the help of tougher laws, officials have moved aggressively this year to shut down so-called pill mills and disrupt the pipeline that moves the drugs north. In the past year, more than 400 clinics were either shut down or closed their doors.

Prosecutors have indicted dozens of pill mill operators, and nearly 80 doctors have seen their licenses suspended for prescribing mass quantities of pills without clear medical need.

New laws are also cutting off distribution. As of July, Florida doctors are barred, with a few exceptions, from dispensing narcotics and addictive medicines in their offices or clinics. As a result, doctors’ purchases of Oxycodone, which reached 32.2 million doses in the first six months of 2010, fell by 97 percent in the same period this year. The ban was phased in beginning last October, with a limit on the number of pills a doctor could dispense.

“We had no tough laws in place; now we do,” said Pam Bondi, Florida’s attorney general.

Law enforcement agencies are also keeping a closer eye on pharmacies. The number of applications to open new pharmacies in Florida has nearly doubled in the past two years, the result of doctors’ facing tougher rules. They now make up half of all the requests in the entire country, according to the latest Drug Enforcement Administration figures.

Now, among other things, background checks are required for owners and employees. Violators, whether they are pharmacists, doctors or clinic owners, face stiffer, swifter penalties if they prescribe or distribute legal narcotic drugs to people who do not need them or without following required steps.

One indication that law enforcement officials are choking the supply of prescription drugs sold illegally in Florida is that the price of Oxycodone on the streets here has nearly doubled from last year, to $15 per pill from $8, according to Capt. Eric Coleman, commander of the narcotics division of the Palm Beach County Sheriff’s Office. And on Commercial Boulevard, a major street in Broward County, the number of pain clinics has fallen in the past year from 29 to one.

Treatment centers are also seeing more addicts seeking help. “We have patients walking in the door that cannot afford prescription drugs any more,” said Dr. Barbara Krantz, the chief executive and medical director of Hanley Center, a large private treatment clinic in Palm Beach County.

Federal, state and local law enforcement officials have worked closely to increase the number of arrests and major indictments. They are dealing with pill mill operators as they would large criminal enterprises.

Last month federal prosecutors used racketeering laws to indict 32 people, including twin brothers who they say operated a sprawling pill mill operation. The brothers, who owned four pain clinics, also were charged with kidnapping, extortion and assault with a firearm under the indictment. Most of the prescriptions were written to patients who traveled to Florida from out of state, with Kentucky making up the largest share.

And in a rare move, a Florida doctor who worked at one of the pain clinics was charged with murder by Palm Beach County prosecutors after a patient died of an overdose in 2009, a few hours after the doctor prescribed him 210 pain pills.

One of the brothers who owned the clinic, Jeffrey George, pleaded guilty to second-degree murder this week. Prosecutors say the twins’ clinics were responsible for 56 overdose deaths.

The clinics were shut in 2010, but more than a year passed before the case was built, in part because Oxycodone is legal and the new laws were not in place.

Charging a doctor and a clinic owner with homicide “was a game changer,” said Sheriff Ric L. Bradshaw of Palm Beach County. “You are not going to get a slap on the wrist. You are looking at life in prison.”

Officials here acknowledge the drug problem is still alarming. Last year, seven people died in Florida each day from prescription drug overdoses, a nearly 8 percent increase from 2009. This is far more than the number who died from illegal drugs, and the figure is not expected to drop much this year. Oxycodone, which when abused has an effect similar to heroin, was the most lethal.