158 SA MEDIESE TYDSKRIF 2 Februarie 1980

Neutralizing Capacity of Commercially Availableand their Role in the Treatm'ent of

Peptic Ulcer

In vitroAntacid Mixtures,

J. E. CLAIN, J. P. WRIGHT, R. N. PRICE, I. N. MARKS

SUMMARY

An in vitro technique has been used to determine theneutralizing capacity of liquid antacids. Many locally avail­able preparations have been tested, and the results indicatethat they vary strikingly in both neutralizing capacity andcost. This study re-emphasizes the place of antacids in

peptic ulcer therapy.

bility was assessed by titrating a single antacid on sixseparate occasions, with a coefficient of variation of 4,1'%.Sodium in each antacid suspension was estimated induplicate in the supernatant of a centrifuged sample usinga flame photometer (Instrumentation Laboratory Inc.,Watertown, Mass) with an internal lithium standard.

RESULTSS. Afr. med. l., 57, 158 (1980).

In spite of the advent of newer agents for the treatment orpeptic ulcer, notably the histamine H,-receptor blockers,antacids remain the most frequently used therapy. Antacidsused in clinical practice are not identical in composition,neutralizing capacity, palatability or price. In this articlewe have set out to evaluate the neutralizing capacity ofmany of the commercially available liquid antacids forcomparative purposes, using a previously described in vitrotechnique.'

MATERIAL AND METHODS

Titrations were performed as follows: each bottle of freshliquid antacid was placed on a mechanical shaker for 10minutes to ensure thorough mixing of the suspension. Onemillilitre of antacid was added to 100 ml of distilled waterat 3JOC in a 250 ml beaker stirred on a magnetic stirrer(Voss Instruments, Essex, UK) at 60 rpm with a 2,5 cmmagnet. A pH electrode attached to an automatic titrator(Radiometer, Copenhagen) recorded the pH constantly inthe stirred mixture. At time zero and at each 5-minuteinterval thereafter O,lM HCl was titrated into the antacidsolution to a pH of 3, and the volume of HCI added wasrecorded. After 1 hour the procedure was performed atlO-minute intervals for a further hour. For each antacidthe experiment was performed in duplicate. The neutra­lizing capacity of an antacid tablet (Gelusil) was similarlyestimated using a crushed aqueous suspension of the tablet.The titration end-point of pH 3 was chosen, since it haspreviously been shown to correlate with the in vivopotency of antacid suspensions.' Experimental reproduci-

Fig. 1 depicts typical titration curves obtained with fourantacid preparations. It will be seen that neutralizationis not immediate, and that for most antacids up to 60minutes is required before all antacid in suspension isneutralized. In the case of Riopone, the titration was notcomplete at 2 hours.

___a-._e_a-.-. CAMAlOX,.---.a

/

ila o_o_o_o-o-o-O-OASllONE

E 30 i 1/_0

-

u a /

; 25 / 0

o • / ...._._.__e-.-.-.-.AMPHOJEl

~ / /0 //a-O~ a /

> / 0 i~ 15/

a/ / ._._.- __.-_GELUS1l

:< ;O/a .•_._~ . ..... .......,. .....,.

~ 10 /i ",.".-.". .If"·

5~V ~

Fig. 1. Titration of 4 antacids with O,lM hydrochloric acid(HCI). One millilitre of antacid was added to 100 ml ofwater at 37° in a 250 ml beaker and the mixture wasstirred at exactly 60 rpm with a magnetic stirrer and a 2,5cm magnet. The pH end-point was 3,0.

TIME (MINUTES)

Gastro-int~tinal Clinic, Groote Schnur Hospital, and De-partment of Medicine, University of Cape Town

J. E. CLAIN, M.B. rn.B.,F.C.P.(S.A.), Senior SpecialistJ. P. WRIGHT, M.B. rn.B., M.R.C.P., SpecialistR. N. PRICE, TechnicianI. N. MARKS, B.se., M.B. rn.B., F.R.C.P., F.A.C.G., Head

Date received: 7 May 1979.Reprint requests to: Dr J. E. Clain. Gastro-intestinal Clinic, OraoleSchuur Hospital, Observatory, 7925 RSA.

20 40 60 se 100 120

2 February 1980 SA MEDICAL JOURNAL 159

TABLE I. TITRATION TO pH 3 OF 1 ml ANTACID WITH O.lM HYDROCHLORIC ACID AT 60 rpm AT 37°C

Volume(0,1tv1 Hel) Neutralizing Volume

capacity required foro min 15 min 60 min 120 min (mmol{ml) 80 mmol

Camalox*t:j: 14,5 23.5 40,2 40.5 4.1 19.5

Asilone*§ 4.0 14,9 32.8 33.6 3,4 23,7

Aludrox*t 4.7 16.9 32.7 32.7 3.3 24.5

Mucaine*t~ 4.6 16.7 31.2 31.3 3,1 26,0

Altacite:j::j: 3,7 12,4 27.9 29,0 2,9 27,8

Maalox*t 5,0 13,8 25,5 26,4 2,6 31.0

Silgastrin Gel'"§tt 8,5 18,8 26,0 26,2 2.6 31.0

Amphojel* 3,0 11,3 23,6 24.0 2,4 33.6

Mylanta'*t§ 4.1 11,5 21.4 22,9 2.3 35,1

Merasyn*t§ 4,3 6.0 20,7 22,7 2,3 35,1

Rlibragel 4,5 12,7 21,1 22,1 2.2 36,7

Kolantyl Gel'tll 4,2 10,3 20,3 20.7 2,1 38,4

Medigel*t§II 5,4 13.7 19,4 20,1 2,0 40,0

Propan Gel-S·tll 4,6 12,8 19,1 19.1 1,9 42,5

Riopone*t 2,3 4,5 11.0 16,5 1,7 47,5

Gelusil* ** 4.3 8,4 13.9 16.0 1,6 50,4

• Aluminium hydroxide. § Methylpolysiloxane. ... Magnesium trisilicate.t Magnesium hydroxide. 1I Dicyclomine HCI. tt Magnesium carbonate.* Calcium carbonate. ~ Oxethazaine. H Not stated.

TABLE 11. COST OF 100 ml AND 80 mmol OF ANTACID

Table I shows the volume of O,lM Hel required tomaintain the pH of 3 at 0, 15, 60 and 120 minutes for allthe antacids tested. The neutralizing capacity of 1 mlantacid under the conditions of this technique is listed indecreasing order. The calculated volume of each prepa­ration required to neutralize 80 mmol of acid is also given.

In Fig. 2 the calculated neutralizing capacity of a 30ml dose of a liquid antacid is compared with that of 2antacid tablets. Table 11 depicts the cost of 100 rnl ofantacid for the various preparations, and the cost ofneutralizing 80 mrnol of acid in increasing order of cost.The sodium content of 30 rnl and 80 mmoI of antacidis shown in Table lIT.

Fig. 2. Relative neutralizing capacities of 30 ml Getusilliquid and 2 Gelusil tablets.

twoGELU.SILTABLETS

JOmlGElUSILLIQUID

50

40

30

48

20

1014

0

-"0EE-

Cost per80 mmol(cents)

1316

1820242526262731

3132

33424453

Cost per100 ml(cents)

55845578797267646584

10091

65180159112

AludroxCamaloxAmphojelMucaineMaaloxMerasynKolantyl GelMedigelPropan Gel-SRubragelSilgastrin GelMylantaGelusilAsiloneAltaciteRiopone

160 SA MEDIESE TVDSKRIF 2 Februarie 19~O

TABLE Ill. SODIUM CONTENT OF 30 rnl AND 80 rnrnolANTACID

Amount of sodium (mmol) in

30 ml antacid 80 mmol antacid

Riopone 0,04 0,07Asilone 0,17 0,13Medigel 0,22 0,29Merasyn 0,34 0,40Carnalox 0,41 0,27Propan Gel-S 0,46 0,65Mylanta 0,50 0,58Altaeite 0,61 0,57Maalox 0,65 0,67Rubragel 0,89 1,09Aludrox 1,09 0,89Mucaine 1,10 0,96Arnphojel 1,12 1,25Gelusil 1,25 2,09Silgastrin Gel 1,42 1,46Kolantyl Gel 1,46 1,87

23 mmol of sodium = 1 g.

DISCUSSION

Antacids have long been the cornerstone of peptic ulcertreatment in the belief that antacids relieve ulcer pain andthat neutralization of acid hastens ulcer healing. Mostclinicians use antacids in an empirical way in the treat­ment of peptic ulcer. Attention has recently been drawnto the magnitude of the neutralizing potential of ant­acids.'" The buffering capacity of food in the stomachmaintains the pH at around 6 for about 1 hour post­prandially.' Antacids given 1 and 3 hours after mealshave been shown to reduce gastric acid considerably,and pH levels are in fact comparable to those after a doseof cimetidine." Since typical duodenal ulcer patients secreteapproximately 40 010101 of acid per hour in response to ameal, it may be argued that a dose of antacid of at least80 010101 is necessary every 2 hours, i.e. 1 and 3 hourspostprandially, to neutralize the acid produced. FromTable I it will be noted that many antacids contain 2 - 3mmol of antacid per ml, and for most a dose of approxi­mately 30 mmol provides the necessary 80 mmol ofneutralizing capacity.

The advent of fibre-optic endoscopy has provided anopportunity for the first time to monitor ulcer healingcarefulty, and Peterson et al." have shown that 30 ml ofantacid given 1 and 3 hours after meals and at night, i.e.7 doses, with a total daily neutralizing capacity of 1 008010101, heals duodenal ulcers more effectively than pla­cebo. Healing on this antacid regimen is comparable tothat achieved with the histamine H,-receptor blocker,cim.etidine.' Such large-volume antacid regimens are cum­bersomeand the recent demonstration of ulcer healing onmuch smaller volumes' (15 011 after meals and at bedtime)and even frequent antacid tablets' (2 tablets, 1 and 3

hours after meals and at bedtime), both with a totalneutralizing capacity of about 175 mmol per day, suggeststhat antacids not only hasten ulcer healing, but may welldo so on more manageable regimens.

Against this background, we thought it relevant to mea­sure the neutralizing capacity of antacids widely used inthis country, using the method of Fordtran et al.' Ourresults are in keeping with those of Fordtran et al. andindicate that there is a marked difference in neutralizingcapacity for the various preparations. Furthermore, con­siderable price differences exist between some preparations,not always based on superior neutralizing capacities.

Some of the more expensive preparati6ns contain anti­cholinergics and/or defoaming agents, which mayor maynot be of therapeutic advantage.

However, cost is not the only factor to be consideredin the choice of an antacid. The sodium content of antacidstested is presented in Table Ill. Riopone and Asilone,although expensive, may be considered in cardiac patientswho require low-sodium antacids. Palatability of antacidsover long periods of time often leads to poor compliance,'·and the use of different antacids sometimes helps in thisrespect. The constipating effect of aluminium hydroxide,and the bowel-loosening effect of magnesium hydroxide,should be borne in mind in individual patients. The neu­tralizing advantage of large doses of calcium-containingantacids should be weighed against the demonstrated dan­gers of hypercalcaemia" and rebound acid secretion."'"

Despite the appreciable acid neutralization achie~ed

with the recommended 5 - 10 011 doses .of antaCIds,a large number of patients clearly require doses largerthan these to control their symptoms. Fig. 3 shows thecalculated neutralizing capacitY of 30 )Ill of the liquidantacid versus 2 antacid tablets, and indicates thatalthough there is considerably less neutralizing capacityin tablets, they still have a definite place in ulcertherapy. Indeed, the study of Lam et al: suggests. that2 antacid tablets given 1 and 3 hours after meals achIevesa duodenal ulcer healing rate similar to that found withintensive antacid or other recognized forms of treatment.In any event there would appear to be little doubtregarding the value of antacids as ulcer therapy.

This report was supported by a grant from the SouthAfrican Medical Research Council.

REFERENCES

1. Fordtran, J. S., Morawski, S. G. and Richardson, C. T. (1973): NewEngl. J. Med., 288. 923. .

2. Fordtran, J. S. and Collyn., J. A. H. (1966): IbId., 274, 921.3. Morri.sey, J. F. and Barrera., R. F. (1974).: IbId., 296, 550.4. Littman, A. and Pine, B. H. (1975): Ann. mtem. Med., 82, 544.5. Deering, T. B. and Malagelada, J-R (1977): Gastroenterology, 73. 11.6. Peter.on, W. L., Sturdevant, R. A. L., Frankl, H. D. et al. (1977):

New Engl. J. Med., 297, 341. . . .7. Ippoliti, A. F., Sturdevant, R. A. L., Isenberg, J. J: et al. (1978).

Gastroenterology, 74. 393.8. Marks, I. N. (1979): S. Afr. med. 1., 55, 331.9. Lam. S. K., Lam, K. C. and Lai, C. L. (1979): Gastroenterology, 76.

315.10. Roth. H. T. and Berger, B. G. (1960): Ibid., 38, 630.11. McMillan, D. E. and Freeman, R. B. (1965): MedICIne, 44, 485.12. Fordtran, J. S. (1'68): New Engl. J. Med., 279. 900.13. Barreras, R. F. (1970): Ihid., 282, 2402.