Formulations and Delivery Systems

TABLE 5.3 Conversion of Animal Dose to Hnman Eqnivalent Dose (HED) Based on Body Snrface Area 

Species To Convert Animal Dose in mg/kg to Dose in mg/m. Multiply by kg/m below To Convert Animal Dose in mg/kg to HED in mg/kg. Either Divide Animal Multiply Animal Dose by Dose by  

Note Column 2 is for information only. For FTED calculations, either column 3 or column 4 is used. 

Apart from pharmacological and toxicological studies, the drug development process encompasses meticulous and methodical work in the following areas  

Most drugs that are prescribed to us are formulated with active pharmaceutical ingredients and excipients. The formulations of selected drugs are presented in Exhibit 5.11. According to the US Pharmacopoeia and National Formulary definition, excipients are any component, other than the active substance(s), intentionally added to the formulation of a dosage form. There are many reasons for the addition of excipients  

HED = animal dose in mg/kg x (animal weight in kilograms / human weight in kilograms)0 33. b This is provided for reference only, as healthy children will rarely be volunteers for Phase I 

Excipients cellulose, disodium hydrogen phosphate, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose, mannitol, sodium lauryl sulfate, etc. 

Excipients starch, gelatin, silicone, titanium dioxide, iron oxide etc. 

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As part of the design proeess, it is neeessary to inelude features in the formulation and delivery system to provide as mueh proteetion as possible against microbial eontaminahon and spoilage. Beeause of potenhal toxicity and irritancy problems, anhmicrobial preservatives should only be considered where there is clear evidence of posihve benefit. Manipulahon of physico-chemical parameters, such as A, the eliminahon of particularly suscephble ingredients, the selection of a preservahve or the choice of container may contribute significantly to overall medicine stability. 

Because dinoprostone produces cervical ripening along with stimulation of the uterus, it has been used as an alternative to oxytocin for the induction of labor. Preparations of dinoprostone can be placed in either the cervix or the posterior fornix. Prepidil is a formulation and delivery system of dinoprostone that delivers a dose of 0.5 mg into the cervix, while Cervidil consists of the drug embedded in a plastic matrix. The matrix is designed to deliver a dose of 0.3 mg per hour for 12 hours. 

Development of improved formulations and delivery systems requires a good understanding of the physical pharmacy of these molecules if we are to avoid typical problems of degradation, unwanted adsorption to glassware and plastics and aggregation in delivery devices such as reservoirs or pumps. 

There are diverse formulations and delivery systems for macrocylic lactones in ruminants, including injectable, oral, sustained-release bolus and transdermal ("pour on") products. In Europe, it is popular clinical practice to administer injectable solutions of ivermectin intravenously (i.v.) to horses. This constitutes extra-label (unlicensed) use and there are no objective data to support the perceived improved efficacy following administration by this route. Specifically, in relation to hypobiotic cyathostome larvae, Klei et al (1993) reported no increase in efficacy when horses were administered 10 pg/kg, which is five times the recommended dose rate. 

Gordon, D.B. (2007) New opioid formulations and delivery systems. Pain Management Nursing, 8, S6—S13. 

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