02/27/2008
Inactive Stuff
First, a correction – mea culpa. Apparently, time flies even when you’re not having fun. In last week’s column, I commented on all the media articles last year on Einstein in commemoration of the hundredth anniversary of his “miracle year”. Einstein’s miracle year was actually in 1905, making the actual hundredth anniversary in 2005. It seems like only yesterday. Obviously, my care giving duties have warped my sense of time.
One of the chores of care giving after her two spinal surgeries and her recent fall has been managing the proper administration of my wife’s medications. Over the past seven months or so these medications have included Nexium, Sucralfate, Amitriptyline, Norvasc, Benicar, Vicodin, Dilaudid, Toprol, Oxycontin, Lyrica, Tylenol 3, Mylanta, Tramadol, Advil, Aleve, Voltaren, and various over the counter laxatives, stool softeners, and other prescription drugs I can’t recall at the moment. It’s somewhat frightening that Heath Ledger’s drug list included essentially all of the drugs my wife has been or had been taking within the recent past!
Just trying to time the delivery of the various meds is a challenge. For example, Nexium suppresses gastric acid production while Mylanta acts as an antacid and Sucralfate forms a sort of patch over an ulcer, according to our pharmacist. One should be taken on an empty stomach, 2 hours after or 1 hour before a meal, another should be taken a half hour before a meal and one should not be taken within a half to an hour after taking another. Mix in the pain meds and it becomes a real balancing act.
The Nexium samples we received came with a very extensive sheet in very fine print describing the contents, uses, precautions, etc., etc. concerning the drug, advertised widely as “The Purple Pill”, a trademark. I was intrigued by the number and identities of the inactive ingredients, having just read a short article by Steve Ritter titled “Excipients” in the January 25 issue of Chemical and Engineering News (C&EN). The main ingredient, known as the “active pharmaceutical ingredient” (API) in the trade, is housed or carried in a mix of inactive ingredients, the excipients. Excipients are roughly a $4 billion dollar a year industry, according to Ritter, quoting a report by BCC Research.
Excipients hold the dose of API together, make sure it’s stable enough to last on the shelf, make sure the API gets delivered in the body at the appropriate time and place and mask any unpleasant taste or odor, etc. Excipients also are used to bulk up a pill and may be mixed with the API to ensure that during the manufacture of the pill each pill contains essentially the same dosage. Excipients known as glidants or granulating agents help the powder mix flow freely in the manufacturing machinery while lubricants or antiadherent excipients keep pressed tablets from sticking to the machinery.
Sometimes you read or hear of cases where a generic form of a drug doesn’t behave exactly as does the original drug. Such cases may involve the use of different excipients. Coatings contain excipients that, for example, may allow the pill to sail through the acidy stomach but dissolve in the less acid intestine. Disintegrants are excipients that expand and dissolve when wet; this allows the tablet to fall apart rather than travel all the way through the body without delivering the API.
Many or most of the excipients used in drugs are byproducts of the food processing industry, according to Ritter. These inactive ingredients have a long track record for safety in foods, beers etc. and don’t have to go through hurdles clearing the FDA. I was interested to read that drug companies tend to stick with the same excipients throughout the life of a patent, one reason being that any change in the formulation has to go back to the FDA for approval.
I got out a magnifying glass to read the inactive ingredients in Nexium and was intrigued with the excipients in the shell (our Nexium comes in a capsule). There are 4 dyes (blue, 2 reds and yellow) that I imagine combine to give the trademark purple color. There are also ethyl, isopropyl and n-butyl alcohols, titanium dioxide, propylene glycol, polyvinyl pyrrolidone, sodium hydroxide and shellac! That’s just in the shell of the capsule. Inside, in addition to the API, is an equally impressive bunch of excipients. There’s a lot of chemistry going on in formulating and manufacturing these drugs.
Needless to say, I’m looking forward to the day when both my wife and I get back to the state where all we have to worry about are our blood pressure, cholesterol, and/or the usual pile of vitamins and other assorted relatively benign pills.
Allen F. Bortrum
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