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BRITISH PHARMACEUTICAL CONFERENCE
697 liver substance, but usually it manifested itself by profuse haematemesis or severe mehcna, as a result of rupture directly into the stomach or duodenum or through the biliary passages ; the rupture is not necessarily fatal at once, and bleeding may recur.20 Jaundice was present in only 36 of the 85 cases studied by Mallory and Jason.19 At operation the aneurysm, which is sometimes intrahepatic, may not be large enough to make its presence felt; the sac, say Mallory and Jason, may vary from the size of a barley-corn to that of a child’s head." Finding such an aneurysm the courageous surgeon, if apparatus for wiring 21 is not at hand, may attempt aneurysmorrhaphy. Gordon-Taylor 20 did this operation successfully, but the patient died forty hours later from other causes. Most surgeons will prefer simple ligation of the hepatic artery.. The ligature must be placed near the origin of the artery to allow anastomotic flow to the liver through its distal branches 22 ; and antibiotics should be given for two weeks or so after operation, to prevent proliferation of anaerobic organisms within the liver.23 Reinhoff and Woods 24 have ligated this artery successfully in 16 of 23 patients with hepatic cirrhosis : which suggests that the low esteem in which the operation was held in pre-antibiotic days is no longer justified. or
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BRITISH PHARMACEUTICAL CONFERENCE
SOME problems in pharmacy received welcome publicity at the British Pharmaceutical Conference in Oxford last month. When. the physician orders a drug in a small dose--many drugs are now made in tablets of 1 mg. or less-he perhaps gives little thought to the manufacturer’s difficulty in ensuring that the drug content of the tablet does not significantly vary from the stated amount. The British Pharmacopoeia Commission, as Mr. T. C. Denston, its secretary, indicated, specifies limits of variation. For a tablet of 100 mg. this limit is plus or minus 10%. More precisely, in any batch of 20 tablets reputed to contain 100 mg. of drug the British Pharmaeopceia requires that 18 shall contain 90-110 mg. of the drug ; the 19th tablet may contain 80-120 mg. ; while the 20th tablet is free from restrictions. For very small quantities of active drug a little more latitude is allowed ; but as better methods of assay are introduced, Thus aneurine so are the official requirements tightened. hydrochloride tablets were formerly assayed fluorimetrically, and the permitted range of variation was 86.5-119% of the stated dose. With the introduction of a more accurate chemical method of assay the permitted range has been narrowed to 925-1075%. Doctor and patient today require less of the dispensing chemist than formerly, as is testified by the low proportion of individually prescriptions found in National Health Service scripts.25 Their demands have been transferred to the manufacturing chemist, in whose advertisements the word " elegant " now frequently figures. Patients now seldom voice the old adage about medicine that " the worse it tastes the better it is for you." But in making his pills palatable the chemist remembers that the premier requirement of a tablet is not a nice taste but guaranteed pharmacological activity. The sugar-coating of penicillin tablets for oral use, to disguise the bitter taste, has been successfully achieved, after rigorous pharmaceutical and pharmacological tests. The coating process itself is simple enough, but before the
designed
20. Gordon-Taylor, G. Brit. med. J. 1943, i, 504. 21. Dwight, R. W., Ratcliffe, J. W. Surgery, 1952, 31, 915. 22. Berman, J. K., Koenig, H., Muller, L. P. Arch. Surg., Chicago, 1951, 63, 379. 23. Tanturi, C., Swigart, L. L., Canepa, J. F. Surg. Gynec. Obstet. 1950, 91, 680. 24. Reinhoff, W. F., Woods, A. C. J. Amer. med. Ass. 1953, 152,
687. 25. See Lancet, Sept. 18, 1954, p. 588.
tablets could be marketed their active penicillin content had to be assayed under all conditions of temperature, humidity, and storage, both in vitro and in vivo. The tests showed that when the sugar-coated tablets were administered two years after manufacture to ten volunteers, the resulting blood and urine levels of penicillin, as shown by plate bio-assay against Sarcina lutea, did not significantly differ from the levels obtained from administration of freshly prepared uncoated
4
penicillin tablets. Another relatively recent field of pharmaceutical enterprise is the " enteric-coated tablet-a term which implies that the contained medicament will not escape in, and thus possibly irritate, the stomach but will be released "
in the upper reaches of the small bowel. Hitherto there has been no guarantee of the reliability of an entericcoated tablet. The British Pharmaceutical Codex, 1954, will, however, introduce a rigorous two-stage in-vitro test for such tablets. In the first stage the tablet is immersed for three hours in a sort of artificial gastric juice-a solution containing pepsin and hydrochloric acid. Having emerged unscathed, or with no greater loss than some fragments of its outer coat, the tablet is placed in an alkaline solution, containing pancreatin, sodium tauroglycholate, and sodium bicarbonate, which is designed to simulate intestinal juice. Here it is given one hour to disintegrate, after which the residuum is passed through a fine gauze sieve in a specially designed apparatus. Only if none of the material is retained by the gauze can the tablet be truly deemed " entericcoated." The British Pharmacopaeia of 1932 included only 1 tablet—glyceryl trinitrate-which had in fact been the only tablet in the Pharm.acopaeia since 1885. Last year’s Pharmaeopceicr had 63 tablets; and the number of unofficial tablets in common use must amount to many hundreds. There are no doubt doctors who pride themselves on their skill in identifying tablets at a glance. But, like other forms of spot diagnosis, this is at best a meretricious accomplishment, at worst a dangerously misleading one. There are many instances-attempted suicide and accidental overdosage are only the two most urgent-when the doctor would dearly like to be able to identify tablets quickly and with certainty. A box containing specimens of tablets, from which the patient identifies the one he has been taking, may sometimes be helpful 26; but clearly this method is often inapplicable and may not be completely dependable.27 Pharmacists are opposed to the colouring of tablets, because this tends to encourage identifying tablets by appearance instead of by scrutiny of the label ; and also because anything should be avoided which makes the pills attractive playthings for young children. But tablets do not always remain in welllabelled containers ; indeed once they are in a patient’s possession they are generally found in a carton which carries no indication of their identity. A possible solution would be for tablets to be stamped with an identity number. This problem is important and is becoming more
important.
_________
Dame JANET CAMPBELL, formerly a senior medical officer at the Ministry of Health, died in London on Sept 27.
WE also regret to announce the death, on Sept. 26, at the age of 74, of Dr. A. W. FALCONER, formerly vicechancellor and principal of the University of Cape Town. Prof. A. BRADFORD
HILL,
D.SC., F.R.S., Prof. G. F.
MARRIAN, D.SC., F.R.S., Prof. G. W. PICKERING, F.R.C.P., and the Hon. R. F. WOOD, M.p., have been appointed members of the Medical Research Council. 26. Russell,
Ibid, 1952, ii, 1254. Cronk, P. G. B., Thorne, N. A. Ibid, 1953, i, 147. 27. Smith, J. C. Ibid, 1953, i, 298. Forster, A. Ibid, p. 445.
z
"
BRITISH PHARMACEUTICAL CONFERENCE
SOME problems in pharmacy received welcome publicity at the British Pharmaceutical Conference in Oxford last month. When. the physician orders a drug in a small dose--many drugs are now made in tablets of 1 mg. or less-he perhaps gives little thought to the manufacturer’s difficulty in ensuring that the drug content of the tablet does not significantly vary from the stated amount. The British Pharmacopoeia Commission, as Mr. T. C. Denston, its secretary, indicated, specifies limits of variation. For a tablet of 100 mg. this limit is plus or minus 10%. More precisely, in any batch of 20 tablets reputed to contain 100 mg. of drug the British Pharmaeopceia requires that 18 shall contain 90-110 mg. of the drug ; the 19th tablet may contain 80-120 mg. ; while the 20th tablet is free from restrictions. For very small quantities of active drug a little more latitude is allowed ; but as better methods of assay are introduced, Thus aneurine so are the official requirements tightened. hydrochloride tablets were formerly assayed fluorimetrically, and the permitted range of variation was 86.5-119% of the stated dose. With the introduction of a more accurate chemical method of assay the permitted range has been narrowed to 925-1075%. Doctor and patient today require less of the dispensing chemist than formerly, as is testified by the low proportion of individually prescriptions found in National Health Service scripts.25 Their demands have been transferred to the manufacturing chemist, in whose advertisements the word " elegant " now frequently figures. Patients now seldom voice the old adage about medicine that " the worse it tastes the better it is for you." But in making his pills palatable the chemist remembers that the premier requirement of a tablet is not a nice taste but guaranteed pharmacological activity. The sugar-coating of penicillin tablets for oral use, to disguise the bitter taste, has been successfully achieved, after rigorous pharmaceutical and pharmacological tests. The coating process itself is simple enough, but before the
designed
20. Gordon-Taylor, G. Brit. med. J. 1943, i, 504. 21. Dwight, R. W., Ratcliffe, J. W. Surgery, 1952, 31, 915. 22. Berman, J. K., Koenig, H., Muller, L. P. Arch. Surg., Chicago, 1951, 63, 379. 23. Tanturi, C., Swigart, L. L., Canepa, J. F. Surg. Gynec. Obstet. 1950, 91, 680. 24. Reinhoff, W. F., Woods, A. C. J. Amer. med. Ass. 1953, 152,
687. 25. See Lancet, Sept. 18, 1954, p. 588.
tablets could be marketed their active penicillin content had to be assayed under all conditions of temperature, humidity, and storage, both in vitro and in vivo. The tests showed that when the sugar-coated tablets were administered two years after manufacture to ten volunteers, the resulting blood and urine levels of penicillin, as shown by plate bio-assay against Sarcina lutea, did not significantly differ from the levels obtained from administration of freshly prepared uncoated
4
penicillin tablets. Another relatively recent field of pharmaceutical enterprise is the " enteric-coated tablet-a term which implies that the contained medicament will not escape in, and thus possibly irritate, the stomach but will be released "
in the upper reaches of the small bowel. Hitherto there has been no guarantee of the reliability of an entericcoated tablet. The British Pharmaceutical Codex, 1954, will, however, introduce a rigorous two-stage in-vitro test for such tablets. In the first stage the tablet is immersed for three hours in a sort of artificial gastric juice-a solution containing pepsin and hydrochloric acid. Having emerged unscathed, or with no greater loss than some fragments of its outer coat, the tablet is placed in an alkaline solution, containing pancreatin, sodium tauroglycholate, and sodium bicarbonate, which is designed to simulate intestinal juice. Here it is given one hour to disintegrate, after which the residuum is passed through a fine gauze sieve in a specially designed apparatus. Only if none of the material is retained by the gauze can the tablet be truly deemed " entericcoated." The British Pharmacopaeia of 1932 included only 1 tablet—glyceryl trinitrate-which had in fact been the only tablet in the Pharm.acopaeia since 1885. Last year’s Pharmaeopceicr had 63 tablets; and the number of unofficial tablets in common use must amount to many hundreds. There are no doubt doctors who pride themselves on their skill in identifying tablets at a glance. But, like other forms of spot diagnosis, this is at best a meretricious accomplishment, at worst a dangerously misleading one. There are many instances-attempted suicide and accidental overdosage are only the two most urgent-when the doctor would dearly like to be able to identify tablets quickly and with certainty. A box containing specimens of tablets, from which the patient identifies the one he has been taking, may sometimes be helpful 26; but clearly this method is often inapplicable and may not be completely dependable.27 Pharmacists are opposed to the colouring of tablets, because this tends to encourage identifying tablets by appearance instead of by scrutiny of the label ; and also because anything should be avoided which makes the pills attractive playthings for young children. But tablets do not always remain in welllabelled containers ; indeed once they are in a patient’s possession they are generally found in a carton which carries no indication of their identity. A possible solution would be for tablets to be stamped with an identity number. This problem is important and is becoming more
important.
_________
Dame JANET CAMPBELL, formerly a senior medical officer at the Ministry of Health, died in London on Sept 27.
WE also regret to announce the death, on Sept. 26, at the age of 74, of Dr. A. W. FALCONER, formerly vicechancellor and principal of the University of Cape Town. Prof. A. BRADFORD
HILL,
D.SC., F.R.S., Prof. G. F.
MARRIAN, D.SC., F.R.S., Prof. G. W. PICKERING, F.R.C.P., and the Hon. R. F. WOOD, M.p., have been appointed members of the Medical Research Council. 26. Russell,
Ibid, 1952, ii, 1254. Cronk, P. G. B., Thorne, N. A. Ibid, 1953, i, 147. 27. Smith, J. C. Ibid, 1953, i, 298. Forster, A. Ibid, p. 445.
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