Extemporaneous liquid preparations

Hydroxyurea is available in 200-, 300-, 400-, and 500-mg capsules. Extemporaneous liquid preparations can be prepared for children who cannot swallow capsules. Doses should start at 10 to 15 mg/kg daily in a single dose, which can be increased... 

A medication available only as a solid dosage form, may be prepared as an extemporaneous liquid (e.g., suspension) or it may be modified for oral use, for example, by crushing. As mentioned previously, a sustained-release product should not be crushed or chewed. For a solid, non-sustained-release medication, the product can be crushed and mixed with a small amount of food just prior to administration. Examples of foods that may be used for mixing include applesauce, yogurt, or instant pudding, but the medication should not be added to an entire dish of food or to infant formula, because the infant or child may not eat/drink the entire portion and thus not receive the total amount of medication. 

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]. 

Quercia RA, Fan Cr Liu X, etaf. Stability of omeprazole in an extemporaneously prepared oral liquid Am J Health SystPharm 1997 54 1833-1836 and Dunn A, White M, Reddy P, et al Delivery of omeprazole and lansoprazole granules through a nasogastric tube in vitro. Am J Health Syst Pharm 1999 56 2327-2330. 

Quercia et al. [171] studied the stability of omeprazole 2 mg/ml in an extemporaneously prepared oral liquid. The contents of five 20-mg omeprazole capsules were mixed with 50 ml of 8.4% sodium bicarbonate solution in a Luer-Lok syringe. Three vials of this liquid were prepared for storage at 24,5, and — 20 °C. A 3-ml sample of each was taken initially and on days 1, 2, 3, 4, 6, 8, 10, 12, 14, 18, 22, 26, and 30 and assayed by HPLC. The liquids stored at 5 and — 20 °C did not change color during the study period, but the color of the liquid stored at 24 °C changed from white to brown. 

Matrix mini-tablets based on starch/microcellulose wax mixtures have been described (31,32). The possibility with these and other mini-tablets is that different dose levels can be administered by changing the number of mini-tablets within a capsule for adults or using single units for children. It is also possible to utilize fast-dissolving mini-tablets to prepare liquid dosages extemporaneously. 

Yamreudeewong, W. Lopez-Anaya, A. Rappaport, H. Stability of fluconazole in an extemporaneously prepared oral liquid. Am.J.Hosp.Pharm., 1993, 50, 2366-2367 [methyl p-hydroxybenzoate (IS) stability-indicating]... 

After water, ethanol is most commonly used in the formulation of oral liquids and is not without risk of acute overdose or chronic intoxication in children. There are still many extemporaneous and commercial preparations containing ethanol as co-solvents administered to children. Adverse effects to the central nervous system because of high blood-brain barrier permeability in children are reported, along with drug interactions linked with acute or chronic exposure. In the USA, the limits are set to a maximum of 10% alcohol in products for 12 year olds and over, a maximum of 5 % alcohol in products intended for children aged 6-12 years and less than 0.5% alcohol content in products intended for children under 6 years of age. Nevertheless, further longterm research is needed to evaluate safety when this excipient is present in the drug formulation. 

Compared to tablets and capsules, oral liquids have some disadvantages as well. Their extemporaneous formulation and preparation is not so easy. They may have an tmpleasant taste, the use of solvents and preservatives is restricted due to their toxicity (especially for children), and the safe use of suspensions requires proper shaking. 

For extemporaneous preparation an aseptic procedure is suitable for the preparation of eye ointments and eye creams in pharmacies. It requires 2 or more Luer-Lock-syringes consecutively conjoined by a sterile Luer-Lock-coimector [127]. By pushing liquid and semisolid intermediate product from one syringe to the other and back through the connector, homogeneous ointments or creams can be prepared (see Fig. 10.5b, c). With the help of additional syringes. 

Extemporaneous preparations, with unknown or uncertain chemical or physical stability, carmot be kept on stock in the pharmacy. They have a maximum usage period according to Table 22.15, but this period is not more than 1 month for liquid and semisolid preparations, and not more than 6 months for dry forms. If the formula is similar to a standardised one, the maximum shelf life of that standardised formula can be used. 

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