Dosage replacement factor

Most active substances possess a higher density than the suppository base. As a result, if dispersed in the base a weight quantity of active substance occupies less volume than the same weight quantity of base. The ratio between both densities is designated as the dosage replacement factor f ... 

If a dosage replacement factor cannot be found in literature it has to be determined. This may be done as follows ... 

The dosage replacement factor f is the displaced amoimt of base per gram of the active substance, so f = (d — c)/a. 

About Dosage Replacement Factor, Density Displacement Factor and Displacement Value... 

In textbooks about suppository preparation not only dosage replacement factors are used but there are also tables with density factors and displacement values. The relation between these terms needs to be clarified. 

The dosage replacement factor (f) of an active substance is the number of parts by weight of hard fat displaced by one part of the active substance. 

Regularly, for the dosage replacement factor (f) other terms are used, for example replacement factor, dose-replacement factor and even displacement factor. The density displacement factor (DDF) is frequently called displacement value the terms displacement factor and density factor are used too. To recognise what authors mean, it is good to realise that mostly f < 1 and DDF = 1/f > 1. 

Sometimes the replacement value is used. This is the weight of base displaced by the active substance (per suppository). Used is also the term displacement value. The replacement value is calculated by multiplying the weight of active substance per suppository by the dosage replacement factor or by dividing the weight of active substance per suppository by the density displacement factor [44]. 

Active substances that are soluble in the suppository base at room temperature, or liquids that are miscible with the suppository base, are incorporated into the base by dissolving in or mixing with the melted base. The calculation of the amount of suppository base is almost the same as with suspension suppositories. In solution-suppositories replacement plays a role if concentrations of active substances are relatively high. If a dosage replacement factor is unknown it has to be determined experimentally. The quantity of excess suppository mass needed may be somewhat smaller than for suspension-suppositories, because the mass can be poured out completely and all the suppositories have the same content. The preparation process steps are almost the same as for fat-based suspension-suppositories, just no dispersion is necessary in summary (see also Sect. 11.5) ... 

Suppose suppositories with 100 mg paracetamol are prepared, incorporated in a fatty base and with a dosage replacement factor f = 0.7 and a suppository weight of 2.00 g. Suppose also that mie cavity of the mold has been filled completely, but as a result of separation during pouring contains 200 mg of paracetamol instead of 100 mg. 

Dosage replacement factor Use standardised batch preparation instruction, use table for dosage replacement factms, determine unknown replacement factors (see 11.5.1)... 

With so many causes of deficiency as just delineated, obviously replacement measures must be matched against ihe causes. A primary objective, where feasible, of course, is to remove or alleviate the causative factors. Also, where Ihere are no contraindication factors, folic acid can be administered in therapeutic dosages. Very small dosages (I mg orally per day) can often be effective. 

As with all forms of long-term therapy, adherence to the prescribed dosage of levothyroxine is not always optimal, and an unwarranted fear of thyroid-induced osteoporosis can add to this lack of adherence. Inadequacy of thyroxine replacement therapy is not always easily recognized. Several patients were reported with clearly inadequate or excessive consumption of levothyroxine despite a correct prescription. All patients had depression, which could be an additional susceptibility factor by promoting lack of adherence, and the resulting hypothyroidism or hyperthyroidism could further aggravate the depression (12). 

Fresh frozen plasma (FFP) 250 ml at six-hour intervals (10-20 ml/kg BW = 1,000-1,500 ml/day). Administration of 10 ml/kg BW (about 600-1,200 rnl) serves to elevate the concentrations of coagulation factors and inhibitors by 15—20%. The half-life of factor VII is only 6 hours, which is why dosage intervals of 6 to 12 hours must be maintained. IgA deficiency is a known contraindication. Adverse transfusion reactions may occur with a frequency of 1-5% of cases. Improvement in coagulopathy generally lasts 1 to 2 days. Caution is called for, since accentuated coagulation entails the danger of thrombosis (if necessary, AT III replacement of up to 60-80%), and an overload of the intra-... 

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