Indian J Pediatr 1989; 56 : 443-445

LETTER TO THE EDITOR

Towards Better Pediatric Drug Formulation The letter of Singhania et al regarding (mis) use of syrups and suspensions in pediatric practice made an interesting and informative reading. 1 However, while comparing the pros and cons of syrups/suspensions vis-a-vis tablets/capsules, they have tended to resort to some generalizations. First of all, the conclusive comment by them that "syrups have no pharmaceutical advantage over tablets", needs reconsideration in light of elaborated pharmacokinetic studies. Apart from various factors operating in gastrointestinal tract, the absorption of a drug ingested depends upon many intrinsic physico-chemical variables of the formulation itself, such as its solubility, rate of dissolution, concentration, partide size, molecular charge at physiologic pH, etc. 2 Usually tablets have to be administered to young children with some sweetened vehicle. Even if crushed, under these circumstances, they may not have predictable absorption, bioavailabUity and hence therapeutic effectiveness) Notterman et al conducted pharmacokinetic studies on three different isoniazid preparations in two young children. They reported that the syrup produced the highest peak ~ncentration (8.3 and 6.9 ~ g/ml), while the crushed tablet in apple-sauce produced the lowest peak concentrations (1.4 and 2.4 u g/ml). In fact this study was stimulated by encountering therapeutic failure with isoniazid tablet in a case of tuberculous meningitis. As far as economic aspect is concerned the cost difference between tablets and sus-

pensions is more marked in case of unpalatable, bitter medicines like furazolidone, metronidazole, chloroquine etc. ~ Though sugar-coating or f'dm-coating techniques have succeeded in disguising these untoward qualities, they do not provide an answer to those pediatric patients who cannot or would not swallow them. Moreover, it is rather impossible to divide these unscored, coated tablets into pieces of desired dosage suited to individual child's requirement. Liquid medications remain one of the most useful forms of drug therapy for such patients. I fully agree with Dr. Singhania et al that standard measures must be provided with liquid preparations for correct dosage administration. The committee on drugs, American Academy of Pediatrics (1975) has strongly recommended use of newer devices, such as molded plastic cylinders, measuring caps and oral syringes for this purpose alongwith use of calibrated droppers and teaspoons.4 Another practical approach to the problem of conventional tablets and syrups is introduction of unit dose sachets and dispersible 'kid' tablets. They are devoid of some of the common drawbacks of dry or prepared syrul?s like improper dilution, inadequate dosage, inappropriate measures, drug wastage etc. But at present their use is restricted mostly to the field of antibiotics. Thus, while pharmaceutical manufacturers should continue vigorous efforts to develop and promote cheap and better alternatives to syrups and suspensions, their usefulness under certain circumstances in 443

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THE INDIAN JOURNAL OF PEDIATRICS

pediatric practice cannot be denied. At the same time, it would be more fair in the larger interest of children if medical practitioners pursue ethical and judicious use of drugs rather than empirical one.s

Dr. B.S. Karnawat Asstt. Professor in Pediatrics ZL.N. Medical College, Ajmer-305001 REFERENCES

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Singhania RU, Bansal A, Sharma JN, Channa RN. Should we continue with the use of syrups and suspensions. Indian J Pediatr 1987; 54 : 126-127 Benet LZ, Sheiner LB. Pharmacokinetics : The dynamics of drug absorption, distribution, and elimination. In: Goodman and Gilman's The Pharmacological Basis of Therapeutics. Ed. Gilman AG, Goodman LS, Rail TW, Murad F. New York, Macmillan Publishing Company, 1985; 3-10 Notterman DA, Nardi M, Saslow JG. Effect of dose formulation on isoniazid absorption in two young children. Pediatrics 1985; 77 : 850-852 Committee on Drugs, American Academy of Pediatrics. Inaccuracies in administering liquid medication. Pediatrics 1975; 56 : 327-328 Karnawat BS. Child Care- Is It Fair? Indian Pediatr 1987; 24 : 171

REPLY BY AUTHOR We thank Dr. Karnawat for the interest shown by him in our article. 1 We endorse his views on better formulations. We have clearly mentioned the need for alternative formulations because of numbers of disadvantages of syrups and suspensions. However, we do agree that at present, we do not have any alternative choice in case of very

Vol. 56, No. 3

small children and infants under certain circumstances elaborated by him. Our statement that syrups and suspensions have no pharamaceutical advantages, over tablets is not an empirical one. A number of factors affect absorption of a drug. which include the physio chemical properties of the drug as well the age of the child and certain behavioural characteristics of children. Certain drugs like phenobarbitone and dilantin are poorly absorbed from the gut whereas those like theophylline and lanoxin are better absorbed in neonates and infantsA 3,4 Quoting from Godman 'n' Gilman "Drugs given in aqueous solutions are more rapidly absorbed than those given in oily base, suspension or solid form because they mix more readily with aqueous phase at the absorptive site". If suspension is not shaken vigarously before use, the amount of drug in the first dose is minimum and the quantity increases in subsequent doses, which may result in non efficiency in early stage and may lead to toxicity in later part of therapy. As for the study by Notterman et al,s we wonder, if it is the vehicle, apple sauce which is interfering with the absorption rather than the drug in tablet form. After exhaustive review of literature we could not locate any other study coroborating the findings of Notterman et al. In our country no liquid preparation of INH has a measure and the cost of equivalent dose is 8 times that of a tablet. We congratulate Dr. Karnawat for giving a be fitting title to the article.

Dr. Rajeshree Singhania Director, L.S.S Pediatric Hospital and Research Centre Jaykaynagar, Kota 324 00. Rajasthan