Extemporaneous suspensions

A decision tree approach for reducing the time to develop and manufacture formulations for the first oral dose in humans has been described by Hariharan et al.86 and is reproduced in Scheme 3.1. The report summarized numerous approaches to the development and manufacture of Phase I formulations. Additional examples of rapid extemporaneous solution or suspension formulations for Phase I studies have been reported.87,88... 

Aubry, A.F., Sebastian, D., Hobson, T., Xu, J.Q., Rabel, S., Xie, M., and Gray, V., In-use testing of extemporaneously prepared suspension of second generation non-nucleoside reversed transcriptase inhibitors in support of Phase I clinical studies, /. Pharm. Biomed. Anal., 23,535,2000. 

Extemporaneous oral suspension Grind four 500 mg oral tablets to a fine powder with a mortar and pestle. Add approximately 10 mL of cherry syrup to the powder and mix until smooth. Transfer the suspension to a graduated amber container. Use several small rinses of cherry syrup to transfer any remaining drug in the mortar to the final suspension for a final volume of 30 mL. The suspension of crushed tablets in artificial cherry syrup (Humco) is stable for 7 days at room temperature. When this suspension is used, shake well before each administration. 

In this book, a number of formulations for made-up suspensions or extemporaneous suspensions produced from instant granules or dry syrups... 

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 preparation of suspensions of drugs available commercially only in other dose forms is widely practised in hospital pharmacy, particularly for paediatric use. Dmgs such as acetazolamide, amiodarone and mercaptopurine are examples. In such formulations, alternatives to traditional suspending agents such as tragacanth should be examined. The ideal suspending agent should ... 

Mathur, L.K. and Wickman, A. (1989) Stability of extemporaneously compounded spironolactone suspensions, Am. J. Hosp. Pharm., 46, 2040-2042. 

Among single drug component studies, usual vehicles for dilution are 5% dextrose (D5W), 0.9% sodium chloride (normal saline, NS), aqueous buffers, peritoneal dialysis fluid, nonaqueous solvents, water for injection, phosphate-buffered saline, bacteriostatic water for injection, bacteriostatic sodium chloride. Ringer s injection, and lactated Ringer s. Stability studies can also be carried out on the drug product solution as such or in specific containers or injection devices. Solutions and suspensions can also be prepared extemporaneously and stability tested to show worthiness for oral, ophthalmic, or rectal administration. The following is an example of the first... 

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. 

To get an idea of the stability of an extemporaneous preparation the only possibility is to keep a part of the preparation in the pharmacy in order to be able to recall if necessary or to have some information in case of a second prescription. For background information on the instability of disperse systems (suspensions, emulsions) and the ways to overcome those stability problems, see Sect. 18.4. For a useful review about the changes in dissolution rate during shelf life and how to prevent them, reference is made to [4]. 

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