Pediatric dosage forms

Extemporaneous production of pediatric dosage forms is commonly undertaken in hospitals. Without the sophisticated formulation capabilities of pharmaceutical manufacturers, alcohol-based vehicles have been recommended for extemporaneous preparation of liquid dosage forms [73]. There is a critical need to conduct research studies to assist the pharmacist in replacing current formulations with stable, alcohol-free preparations [74]. 

Smell, taste, texture, and aftertaste, therefore, are important factors in the development of pediatric dosage forms. In a study of six brands of OTC chewable vitamins, flavor type and intensity, soft texture, and short aftertaste were critical factors in product preference. The flavor and texture attributes of the bestselling product were significantly different from the other brands [97]. 

The critical void in pediatric drug therapy now lies in effective drug-delivery systems. Some inroads have been made in the manufacturing of pediatric dosing systems, particularly OTC preparations. There needs to be a redirection of the focus in nonparenteral drug formulations towards pediatric dosage forms with proven stability and bioavailability that can be easily and accurately administered to infants and children. 

Suspensions are two-phase systems consisting of a finely divided solid dispersed in a liquid, solid, or a gas (Table 6). They are appropriate when the drug to be incorporated is not sufficiently soluble in an ordinary solvent or cosolvent system. They are used orally and topically. Examples of compounded suspensions include pediatric oral liquids where a commercial pediatric dosage form is not available. Commercial tablets and capsules are formulated into a vehicle and can be individually flavored to the patient s preference. 

The early commercial penicillin was a yellow to brown amorphous powder that was so unstable that refrigeration was required to maintain a reasonable level of activity for a short time. Improved purification procedures provided the white crystalline material in use today. Crystalline penicillin must be protected from moisture, but when kept dry, the salts will remain stable for years without refrigeration. Many penicillins have an unpleasant taste, which must be overcome in the formation of pediatric dosage forms. All of the... 

In this chapter some changes that are pertinent in the development of pediatric dosage forms will be highlighted. 

Drug absorption is highly variable in neonates and infants [21,22]. Older children appear to have absorption patterns similar to adults unless chronic illness or surgical procedures alter absorption. Differences in bile excretion, bowel length, and surface area probably contribute to the reduced bioavailability of cyclosporine seen in pediatric liver transplant patients [22a]. Impaired absorption has also been observed in severely malnourished children [22b]. A rapid GI transit time may contribute to the malabsorption of carbamazepine tablets, which has been reported in a child [23]. Selection of a more readily available bioavailable dosage form, such as chewable tablets or liquids, should be promoted for pediatric patients. 

Both solid and liquid dosage forms may contain saccharin. Saccharin is a nonnutritive sweetening agent, which is 300 times as sweet as sucrose. In a survey of sweetener content of pediatric medications, seven out of nine chewable tablets contained saccharin (0.45-8.0 mg/tablet) and sucrose or mannitol. Seventy-four of the 150 liquid preparations investigated contained saccharin (1.25-33 mg/5 mL) [62], Saccharin is a sulfanamide derivative that should be avoided in children with sulfa allergies [54],... 

Because of the high incidence of lactose intolerance in the general population, lactose is not recommended as a sweetener for pediatric populations [70]. Aspartame, a phenylalanine derivative, is incorporated in many chewable tablets and sugar-free dosage forms. Aspartame-containing products should be avoided in children with autosomal recessive phenylketonuria [54]. 

Oral Administration. Oral administration is the preferred route of administration. There is a general consensus among pediatricians and parents that children younger that 5 years of age have great difficulty with, or are unable to swallow, a solid oral dosage form. Manufacturers, therefore, have developed liquid formulations for many of the commonly used pediatric products. The liquid dosage form, however, is not free of problems. Liquid products are often unstable and have short expiration dates accurate measurement and administration of the prescribed dose is also a problem, especially in infants. 

Rectal Administration. The administration of drugs by a solid rectal dosage form (i.e., suppositories) results in a wide variability in the rate and extent of absorption in children [79]. This fact, coupled with the inflexibility of a fixed dose, makes this a route that should not be promoted for pediatric patients. At least one death involving a 7-month-old infant can be directly attributed to the use of solid rectal dosage form of a therapeutic dose of morphine [80]. 

The dosage forms most commonly employed for pediatric formulations are liquids and chewable tablets. A perceived unpleasant taste is much more evident with these dosage forms than when a drug is administered as a conventional solid oral dosage form. Second, it is widely believed that children younger than the age of 6 years have more acute taste perception than older children and adults. Taste buds and olfactory receptors are fully developed in early infancy. Loss of taste perception accompanies the aging process. 

The development of oral dosage forms that disintegrate or dissolve in the mouth is providing LCM opportunities for pediatric, geriatric, or bedridden patients who have difficulty in swallowing. They are also being used by active adult patients who may not have ready access to water for swallowing tablets or capsules. 

Even if a medication is available in multiple formulations and dosage forms, the prescriber must consider the absorption and distribution differences between adult and pediatric patients. Blood supply at injection or infusion site, available blood supply for unit muscle mass, and skeletal muscle mass relative to body mass vary with patient age and size, causing drug absorption to vary, as well. A rapid intravenous bolus in a pediatric patient might result in acute toxicity a slow intravenous infusion, often required in neonates, can cause erratic, unreliable drug delivery in an older child. In addition, the volume of fluid tolerated for intravenous delivery varies significantly with the age and size of the patient. The blood supply and blood flow to and from the injection site are of prime importance since a gradual decrease in blood supply per unit muscle mass is seen with maturation. In addition, the skeletal muscle mass relative to... 

Dosage forms Lupron Injection and Lupron Injection Pediatric are sterile. 

The usual adult dosage of the micronized ("microsize") form of the drug is 500 mg daily in single or divided doses with meals occasionally, 1 g/d is indicated in the treatment of recalcitrant infections. The pediatric dosage is 10 mg/kg of body weight daily in single or divided doses with meals. An oral suspension is available for use in children. 

Drug Strength Dosage form Pediatric dosing Therapy or prophylaxis Disease... 

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