PAEDIATRIC FORMULATIONS OR EXTEMPORANEOUS DOSAGE FORM FOR ORAL LIQUIDS
About Author: Riddhi M. Katira1, Vipul P. Patel3, Tushar R. Desai4
1. Authour, R.K. College of Pharmacy, Kasturbadham, Rajkot.
2. Assistant professor, Department of pharmaceutics, R.K. College of Pharmacy, Kasturbadham, Rajkot.
3. Principal, Department of pharmacology, R.K. College of Pharmacy, Kasturbadham, Rajkot.
Appropriate for use in this population. These drugs may be prepared extemporaneously for use in individual patients. Physical and chemical properties of drugs and excipients should be considered when preparing extemporaneous formulations. These formulations, however, may lack studies to document stability, bioavailability, pharmacokinetics, pharmacodynamics, efficacy, and tolerability.
Drug substances are usually administered as part of a formulation in combination with; nonmedical agents (otherwise known as inactive pharmaceutical ingredients or excipients) that have varied, specialized pharmaceutical functions. The proper design and formulation of a dosage form requires consideration of the physical, chemical, and biological characteristics of all drug substances and pharmaceutical ingredients to be used in formulating the product. The drug and pharmaceutical materials utilized must be compatible with one another to produce a drug product that is stable, efficacious, palatable, easy to administer, and well tolerated. The age of the intended patient also plays a role in dosage form design. Infants and children aged ~5 years or younger are unable to swallow a solid dosage form (eg, tablet, capsule). A solid dosage form containing a fixed dose (eg, 250 mg) would also be impractical to use in these patients because the dosage requirements vary based on body weight (eg, milligram, kilogram) or surface area (milligram!meter2 ). Thus, pharmaceutical liquids, rather than solid dosage forms, are preferred for oral administration to infants and young children. A single liquid pediatric preparation may be used for infants and children of all ages, with the dose of the drug varied by the volume administered. 
In the absence of a ready-made product a frequent approach by pharmacists is to prepare an oral liquid from tablets, capsules or powdered drug dispersed or dissolved in a suitable base. These are often referred to as extemporaneously prepared formulations and the practice occurs on an international scale. A survey of 210 pharmacists in the USA identified the eleven most frequently compounded preparations and the authors concluded that efforts by manufacturers and professional associations are required to supply pharmacists with information on the compounding and stability of extemporaneous preparations. 
Stewart and Tucker surveyed Australian hospitals and showed that 116 drugs were extemporaneously compounded into 270 different formulations for paediatric use. Frequent problems identified in this survey included disguising unpleasant taste, achieving dose uniformity and a lack of chemical and physical stability data. This lack of stability information is a common problem and formularies of extemporaneous formulations have been published in an attempt to provide some guidance on the preparation of paediatric oral liquids. 
LACK OF COMMERCIAL PRODUCTS AND THE IMPLICATIONS FOR INFANTS AND CHILDREN
Unless an illness largely affects infants and children, most drugs are not labeled for use in the pediatric population for a variety of reasons. These include relatively small market size (thus limiting return on investment), potential delay in marketing a drug for adults, and perception of greater legal liability and regulatory requirements for conducting studies in children instead of in adults. Consequently, nearly 75% of the drugs available in the United States for adults have not been labeled for use in infants and children (ie, those aged <12 years), even though these drugs may be needed in this population. [4,5] For example, seizure disorders occur in both adult and pediatric patients, but certain drugs-gabapentin, lamotrigine, tiagabine, and topiramate-were not fully labeled or available in a liquid dosage form for use in young pediatric patients (ie, those aged <12 years) at the time of their marketing for adults. Also, sildenafil was found to be effective in adults for the treatment of pulmonary hypertension, but it was not available in a liquid dosage form for use in neonates with this condition. Extemporaneous liquid formulations prepared from solid dosage forms were needed to make these drugs accessible to infants and children. 6 IV drugs (eg, morphine, phenobarbital) marketed for adults are too concentrated for accurate measurement of the small volumes (doses) needed for the treatment of neonates or infants. These drugs need to be diluted to minimize underdosing or overdosing; however, stability and sterility of these extemporaneously prepared formulations for parenteral use must be documented before administration to patients. 
When drugs are not commercially available in appropriate dosage forms, options include the following: delaying or omitting potentially effective therapies; us-ing a dosage form intended for adults without alteration; contacting the manufacturer for recommendations; and preparing an extemporaneous formulation, if reasonable, based on data in the literature or in consultation with peers. Examples of drugs not commercially available in suitable dosage form (ie, a liquid formulation) for infants and young children are listed in the table. 
NEED FOR PEDIATRIC DRUG FORMULATIONS
Based on a survey of 57 hospitals, with 36 to 350 licensed pediatric beds, there was a need for >100 liquid formulations for use in pediatric patients. Similarly, a United States Pharmacopeia (USP) survey identified the need for >70 formulations for oral administration in infants and children (personal communication, Claudia Okeke, PhD, Rockville, Maryland, January 15, 2008). The need is expected to grow because the majority of newly approved drugs are not labeled for use in pediatric patients, and an appropriate formulation usually does not exist unless the drug is approved for that population.