Griseofulvin Solubility, Particle, Matrix, and Dose

Griseofulvin occurs as a white to creamy white, odorless powder, in which particles of the order of 4 micron in diameter predominate. It has a potency equivalent of not less than 900 microgram/mg of griseofulvin. It is very slightly soluble in water. "Very slightly soluble" is defined as 1 part in 1,000 to 10,000 parts (1 g in 1,000 to 10,000 mL of water). Commercial forms and their relative doses include:

Note: The ultramicrosize griseofulvin is composed of ultramicrosize crystals of griseofulvin dispersed in polyethylene glycol 6000 or dispersed by other suitable means.

As is evident, there is a decrease in dose with a decrease in particle size. When the particle size of a very poorly soluble drug is decreased, there is a tendency for the particles to agglomerate. By incorporating the very small particle size into polyethylene glycol, which tends to surround/coat the particles of griseofulvin, the particles are separated, and, when they are placed in a fluid environment, they are wetted better and dissolve much faster for absorption.

A decrease in particle size may or may not enhance bioavailability; it depends upon other factors such as wettability, agglomeration, etc.

Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition

Negative List Clarification

In the current issue of IJPC, the article "Basics of Compounding: The "Negative" List," applies only to compounding for human patients. The Negative List is required by DQSA which applies to humans only. The list will be updated as necessary.

The decisions made by the Pharmacy Compounding Advisory Committee (PCAC) are only advisory. All drugs added to either the positive or negative list will still have to go through a Notice and Comment Rule Making process. On a rolling basis, the FDA will issue a proposed rule for drugs added to a list and will invite public comments. Public comments, by law, have to be reviewed and responded to. Once this is completed, the FDA will issue a Final Rule for enforcement. Note: No proposed rules have been issued for the work of the current PCAC.

News

Midazolam Nasal Spray and Seizures
A nasal spray formulation of midazolam may diminish repeated seizures and lower the risk of generalized tonic-clonic seizures in hospitalized epilepsy patients, researchers found. They stated that only four of 75 patients had an adverse event; there were no serious adverse events and the treatment was generally well-tolerated.

The nasal spray was prepared at the hospital's pharmacy and delivered a dose of 2.5 mg midazolam per puff. The average dose per patient was 5 mg, or two sprays. Those given intranasal midazolam during or right after a seizure remained free of seizures longer than those not given the drug (5.83 hours versus 2.37 hours).
http://www.medpagetoday.com/Neurology/Seizures/52830

Pharmacy Robberies Increase
Pharmacy robberies across the nation are outpacing last year's robberies with Indiana leading the way. Many are carried out by people doing whatever they can to feed their addiction, while others are part of an organized retail crime group. More robberies have occurred in the first five months of 2015 than during the same time frame of 2014, the U.S. DEA said. There were 382 armed robberies of pharmacies reported from January to June of this year, outpacing the monthly rate of last year by about seven per month.

Top 10 states of pharmacy robberies: Indiana (68); Wisconsin (32); California (31); North Carolina (21); Georgia (12); Maryland (12); Texas (12); South Carolina (11); Tennessee (11); Arizona (9).
http://www.journalgazette.net/news/local/police-fire/Pharmacy-heists-hit-an-unwanted-high-7900336

Express Scripts Posted Modest Revenue Increase to $25.45 Billion
Overall, the company reported a profit of $600.1 million, or 88 cents a share, up from $515.2 million, or 67 cents a share, a year earlier. The number of adjusted claims filled in retail pharmacies and 90-day fills through the company's mail-order business fell 1% to 321.2 million. Revenue increased to $25.45 billion from $25.11 billion.
http://www.wsj.com/articles/express-scripts-raises-guidance-as-earnings-top-views-1438116544?cb=logged0.4972025179539459

Express Scripts Complains About Costly New Cholesterol Drugs
Express Scripts said the cost of potent, newly approved cholesterol drugs could "wreak financial havoc" among its clients. U.S. regulators approved the first of the new medicines, Praluent, from Regeneron Pharmaceuticals Inc. and Sanofi SA. Given every other week by injection, Regeneron said that Praluent will have a wholesale price of $1,120 for a 28-day supply. That comes to almost $15,000 a year.

Standard older cholesterol fighters such as statins, including generic forms of Pfizer Inc.'s Lipitor and Merck & Co.'s Zocor, can cost less than $50 a month.

Glen Stettin, a senior Express Scripts executive, said an estimated 70 million Americans have high cholesterol, but he estimates fewer than 10% of them should qualify for Praluent. Before getting their prescriptions filled, patients in Express Scripts plans will be asked for documentation of their diagnosis, their cholesterol levels, diet, and maximum tolerated statin therapy, Stettin said.
http://www.reuters.com/article/2015/07/29/us-express-scr-cholesterol-idUSKCN0Q321520150729

Some Mexican Cilantro Banned After Feces Found in Fields
The FDA is banning imports of some fresh cilantro from Puebla, Mexico, after a government investigation found human feces and toilet paper in growing fields there. The FDA announced the partial ban Monday after cilantro imported from the state of Puebla was linked to 2013 and 2014 outbreaks of stomach illnesses in the U.S. The FDA said the officials discovered the feces and toilet paper in fields and found that some of the farms had no running water or toilet facilities.
http://www.washingtontimes.com/news/2015/jul/27/fda-bans-some-mexican-cilantro-after-feces-found-i/

European Union Bans Hundreds of Drugs Over Clinical Trial Flawed Studies
The European Union has accepted a recommendation to suspend hundreds of drugs that were authorized for use based on what regulators called "flawed" studies conducted by GVK Biosciences, a clinical research organization based in Hyderabad, India. As previously noted, the issue emerged after an inspection a year ago by French regulators raised concerns about the reliability of several studies conducted on behalf of several drug makers by GVK between 2008 and 2014. The EMA recommended suspension as a precautionary measure, since there was no evidence of patient harm or a lack of effectiveness linked to the studies.
http://blogs.wsj.com/pharmalot/2015/07/27/european-union-upholds-ema-recommendation-to-ban-hundreds-of-drugs/

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Did You Know ...

�that it seems that many people today are willing to "ride the wave" of the newest poorly documented issues of the day from politics to the universe?

Tip of the Week

Don't forget the foundations that have already stood the test of time and valuable critiques to get us where we are today. How can we, with our very limited and imperfect knowledge, but huge egos, simply discard them?

Looking Back

The monkey took,
One look at Jim
And threw the peanuts
Back at him!
He needed�
     Burma Shave