Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5576_Библиотеки_им_академика_М_И_Перельмана
.pdf
Common instruments for the pharmaceutical measurement of volume
range from micropipettes and burettes used in analytic procedures to large,
industrial-size calibrated vessels. The selection of measuring instrument
should be based on the level of precision required. In pharmacy practice,
the most common instruments for measuring volume are cylindrical and
conical (cone-shaped) graduates (Fig. 3.1). For the measurement of small
volumes, however, the pharmacist often uses a calibrated syringe or, when
required, a pipette.
FIGURE 3.1 Examples of conical and cylindrical graduates, a
pipette, and a pipette-filling bulb for volumetric measurement.
Whereas cylindrical graduates are calibrated in SI or metric units, conical
graduates are usually dual scale, that is, calibrated in both metric and
apothecary units of volume. Both glass and plastic graduates are
commercially available in a number of capacities, ranging from 5 to 1000
mL and greater.
As a general rule, it is best to select the graduate with a capacity equal
to or just exceeding the volume to be measured. Measurement of small
volumes in large graduates increases the potential for error. The design of a
volumetric apparatus is an important factor in measurement accuracy; the
narrower the bore or chamber, the lesser the error in reading the meniscus
and the more accurate the measurement (Fig. 3.2). According to the United
States Pharmacopeia, a deviation of ±1 mm in the reading of the meniscus
when using a 100-mL cylindrical graduate results in an error of
approximately 0.5 mL and 1.8 mL at the 100-mL mark when using a 125mL conical graduate.
1
FIGURE 3.2 Volume error differentials due to instrument
diameters. (A) Volumetric pipette; (B) cylindrical graduate; and
(C) conical graduate.
It is essential for the pharmacist to select the proper type and capacity of
instrument for volumetric measure and to carefully observe the meniscus at
eye level to achieve the desired measurement.
Measurement of Weight
There is a wide range of weights, balances, and scales available for
pharmaceutical measurement. The proper selection depends upon the
particular task at hand. Standard prescription balances and highly sensitive
electronic balances generally suffice in traditional pharmaceutical
compounding, whereas large-capacity scales are used in the industrial
manufacture of pharmaceutical products. Whichever instrument is used,
however, it must meet established standards for sensitivity, accuracy, and
capacity.
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
A differentiation may be made between a scale and a balance. A scale
measures a single object’s weight (think of a bathroom scale). A scale
reading will differ if the gravity is different, that is, less at higher
elevations and greater at sea level. A balance uses a lever and fulcrum, or a
pivoting point, to compare the masses of two different objects. A weight of
known mass is used to measure the substance being weighed. A balance is
more precise than a scale. Analytical balances are characterized by a
precision/capacity ratio of 1/500,000 or better and a readability of 0.1 mg
or better. Microbalances have readabilities as low as 0.001 mg, and
ultramicrobalances have readabilities as low as 0.0001 mg.
a
a
Balances of all types are available from several manufacturers including OHAUS
Corporation (https://us.ohaus.com/en-US/products-13), Sartorius Corporation
(https://www.sartorius.com/us-en/products/weighing), and A&D Weighing
(http://www.andonline.com/weighing/).
Some terminology associated with balances and scales is presented in
Table 3.1.
TABLE 3.1 SOME TERMINOLOGY ASSOCIATED WITH
BALANCES AND SCALES
a
a
Sources: Scales Online, https://www.scalesonline.com/ScaleTerminology;
and USP 43/NF 38, General Chapters. <1251> Weighing on an Analytical
Balance.
Class A prescription balances (Fig. 3.3) are designed for the weighing of
medicinal or pharmaceutical substances required in the filling of
prescriptions or in small-scale compounding. Some prescription balances
have a weighbeam and rider, and others a dial, to add up to 1 g of weight.
As required, additional external weights may be added to the right-hand
balance pan. The material to be weighed is placed on the left-hand pan.
Powder papers are added to each pan before any additions, and the balance
is leveled by leveling feet or balancing screws. Weighings are performed
through the careful portion-wise (by spatula) addition and removal of the
material being weighed, with the balance being arrested (pans locked in
place by the control knob) during each addition and removal of material
and unarrested with the lid closed for determinations of balance rest points.
When the unarrested pans neither ascend nor descend, and the index plate
shows the needle is in the center, the material and balance weights are
considered equivalent. The student may wish to refer to other sources, such
as the United States Pharmacopeia, for more detailed information on the
proper use and testing of the prescription balance.
1
FIGURE 3.3 Torbal torsion balance. (Courtesy of Scientific
Industries, Torbal Division.)
Minimally, a Class A prescription balance should be used in all
prescription compounding procedures. Balances of this type have a
sensitivity requirement (SR) of 6 mg or less with no load and with a load
of 10 g in each pan. To avoid errors of >5% when using this balance, the
pharmacist should not weigh <120 mg of material (i.e., a 5% error in a
weighing of 120 mg = 6 mg). Most commercially available Class A
balances have a maximum capacity of 120 g.
The term sensitivity requirement is defined as the load that will cause
a change of one division on the index plate of the balance. It may be
determined by the following procedure:
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
1. Level the balance.
2. Determine the rest point of the balance.
3. Determine the smallest weight that causes the rest point to shift one
division on the index plate.
For greater accuracy than a Class A prescription balance allows, many
pharmacies utilize high-precision electronic analytical balances to weigh
very small quantities (Fig. 3.4). Many of these balances are capable of
accurately weighing 0.1 mg, are self-calibrating, and are equipped with
convenient digital readout features. The usual maximum capacities for
balances of this precision range from about 60 to 210 g depending upon the
model. A set of metric weights that may be used to weigh materials on a
prescription balance and/or used to calibrate an analytical balance is shown
in Figure 3.5.
FIGURE 3.4 Sartorius BasicLite analytical balance. (Copyright
© Sartorius AG. Image provided by courtesy of Sartorius AG.)
FIGURE 3.5 Set of metric weights. (Courtesy of MettlerToledo, Inc.)
Aliquot Method of Weighing and Measuring
When a degree of precision in measurement that is beyond the capacity of
the instrument at hand is required, the pharmacist may achieve the desired
precision by calculating and measuring in terms of aliquot parts. An
aliquot is a fraction, portion, or part that is contained an exact number of
times in another.
Weighing by the Aliquot Method
The aliquot method of weighing is a method by which small quantities of
a substance may be obtained within the desired degree of accuracy by
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
weighing a larger-than-needed portion of the substance, diluting it with an
inert material, and then weighing a portion (aliquot) of the mixture
calculated to contain the desired amount of the needed substance. A
stepwise description of the procedure is depicted in Figure 3.6 and is
described as follows:
FIGURE 3.6 Depiction of the aliquot method of weighing using
the example described in the text.
Preliminary Step. Calculate the smallest quantity of a substance that
can be weighed on the balance with the desired precision.
The equation used:
On a balance with an SR of 6 mg, and with an acceptable error of no >5%,
a quantity of not <120 mg must be weighed.
Step 1. Multiply the desired quantity by a factor that will produce a
quantity that can be weighed with the required precision.
If the quantity of an active ingredient is less than the minimum
weighable amount determine a “multiplier” for the required quantity that
will yield an amount equal to or greater than the minimum weighable
amount. Ideally, the amount to be weighed should be a quantity that can be
accurately measured by the instrument to be used (i.e., a whole number
rather than a decimal fraction). A larger-than-necessary multiplier may be
used to exceed the minimum accuracy desired, but should not produce an
amount that is more than two times greater than the minimum weighable
amount to avoid using an unnecessary amount of active ingredient.
Example:
Using the balance in the example in the preliminary step, what
multiplier should be used to weigh 5 mg of a drug substance?
A multiplier of 24 can be used as follows:
5 mg × 24 = 120 mg, which would produce an amount that can be
weighed with the desired 5% accuracy
A multiplier of 30 can also be used:
5 mg × 30 = 150 mg, which would produce an amount that can be
accurately weighed without too much waste
A multiplier of 20 would produce the following result:
5 mg × 20 = 100 mg, which would be an amount less than the
minimum weighable amount
A multiplier of 50 would produce an excessive amount of the drug as
shown:
5 mg × 50 = 250 mg, which is more than twice the minimum
weighable amount
STEP 2. Select an aliquot amount that can be weighed with the required
precision.
The guidelines for selecting the aliquot amount are as follows:
The amount should be equal to or greater than the minimum
weighable amount determined in the preliminary step.
The amount should be a quantity that can be accurately measured by
the instrument to be used (i.e., a whole number rather than a decimal
fraction).
The amount should not be larger than twice the minimum weighable
amount to avoid using an unnecessary amount of diluent.
Example:
According to the preliminary step, 120 mg or more must be weighed
for the desired accuracy. Therefore, any whole number between 120
and 240 mg (e.g., 140 mg) can be chosen for the aliquot.
STEP 3. Determine the amount of inert diluent to add to the active
ingredient.
The total weight to which to dilute the active ingredient is determined
by multiplying the weight of the aliquot selected in Step 2 by the multiplier
used in Step 1. The amount of diluent is then calculated by subtracting the
amount of active ingredient determined in Step 1 from the total weight of
the dilution.
Example:
If we decide on 140 mg for the aliquot portion in Step 2, and multiply
it by the multiplier selected in Step 1 (i.e., 24), we arrive at 3360 mg
for the total quantity of the drug–diluent mixture to prepare.
Subtracting 120 mg of drug weighed in Step 1, we must add 3240 mg
of diluent to prepare the 3360 mg of drug–diluent mixture.
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
STEP 4. Clearly convey the quantities calculated and check for
accuracy.
The quantities calculated previously should be clearly written,
preferably in steps, as follows:
1. Weigh amount determined in Step 1 of active ingredient.
2. Weigh amount determined in Step 3 of diluent.
3. Combine active ingredient and diluent. Mix thoroughly.
4. Weigh aliquot amount determined in Step 2 from mixture.
The steps mentioned can be checked for accuracy using the following
formula:
If the answer to this formula results in the amount of active ingredient
initially required in the preparation, then the correct numbers have been
conveyed and calculated in the process.
Example:
Listing the quantities calculated in clear instructions:
Weigh 120 mg of drug
Weigh 3240 mg of diluent
Combine drug and diluent. Mix thoroughly.
Weigh 140 mg from the mixture to obtain 5 mg of drug.
Proof:
Example Problems
1. A torsion prescription balance has a sensitivity requirement of 6 mg.
Explain how you would weigh 4 mg of atropine sulfate with an
accuracy of ±5%, using lactose as the diluent.
Because 6 mg is the potential balance error, 120 mg is the smallest
amount that should be weighed to achieve the required precision as
shown in the previous example problem.
STEP 1. Choosing 30 as the multiplier, the amount of drug to weigh
would be:
4 mg atropine sulfate × 30 = 120 mg atropine sulfate to weigh
STEP 2. The weight of the aliquot can arbitrarily be set as 150 mg.
STEP 3. The weight of lactose can be determined as follows:
150 mg aliquot × 30 = 4500 mg dilution
4500 mg dilution – 120 mg atropine sulfate = 4380 mg × 1 g/1000 mg
= 4.38 g lactose
STEP 4. The directions for weighing utilizing the amounts calculated
previously are shown here:
Weigh 120 mg of atropine sulfate.
Weigh 4.38 g of lactose.
Combine atropine sulfate and lactose. Mix thoroughly.
Weigh 150-mg aliquot from mixture to obtain 4 mg atropine sulfate.
Proof:
In this example, the weight of the aliquot was arbitrarily set as 150
mg, which exceeds the weight of the multiple quantity. If 120 mg had
been set as the aliquot, the multiple quantity should have been diluted
with 3480 mg (3.48 g) of lactose to get 3600 mg of dilution, and the
aliquot of 120 mg would have contained 4 mg of atropine sulfate.
2. An electronic balance has a sensitivity requirement of 2.5 mg. Explain
how you would weigh 1.5 mg of hyoscyamine sulfate with an accuracy
of ±5%, using lactose as the diluent.
Preliminary Step.
STEP 1. Choosing 40 as the multiplier, the amount of drug to weigh
would be:
1.5 mg hyoscyamine sulfate × 40 = 60 mg hyoscyamine sulfate to
weigh
STEP 2. The weight of the aliquot can be set as 50 mg.
STEP 3. The weight of lactose can be determined as follows:
50 mg aliquot × 40 = 2000 mg dilution
2000 mg dilution – 60 mg hyoscyamine sulfate = 1940 mg × 1 g/1000
mg = 1.94 g lactose
Step 4. The directions for weighing utilizing the amounts calculated
previously are shown here:
Weigh 60 mg of hyoscyamine sulfate.
Weigh 1.94 g of lactose.
Combine hyoscyamine sulfate and lactose. Mix thoroughly.
Weigh 50-mg aliquot from mixture to obtain 1.5 mg hyoscyamine
sulfate.
Proof:
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Соседние файлы в папке Библиотека им академика М.И. Перельмана