Quality Control Lab Manual Answers

INSTRUMENTAL METHOD

#9

1. Define Spectrometry? Spectrophotometry?

Spectrometry may be defined as methods of analysis which deals with the
measurement of spectra. In pharmaceutical analysis the more common
measurements which are made of spectra and which are aspects of
spectrometry are measurements of the position in the electromagnetic
spectrum where radiant energy has interacted with a chemical species and
measurement of transmitted, fluorescent reflected or emitted energy.
Spectrophotometry is a branch of spectrometry which embraces the
measurements of the absorption by chemical species of radiant energy of
definite and narrow wavelength approximating monochromatic radiation.
2. What are the difficult ranges of the wavelength of radiant energy?
The ranges of the wavelength of radiant energy of importance in the practice
of spectrophotometry are:
UV-220-380nm
Visible-380-780nm
Near IR-780-3000nm
Medium-3.0-15um
Far IR-15-300um
3. State the general spectrophotometric procedure?
The general spectrophotometric procedure involves the preparation of the
spectral absorbance curve (SA curve) of the analyte. This curve is made
plotting the absorbance of the analyte versus the wave length. The
absorbance value is usually determined at 5nm increments except in the
region of the maximum where 2nm increments are used after the SA curve
has been prepared the wavelength at which maximum absorption occurs is
chosen for the purpose of measuring absorbance values of a series of
reference solute concentrations.

INSTRUMENTAL METHOD

#10

1. What is pH?
A special name is given to the acid or base characteristic that a
substance has. p stands for potential and H stands for hydrogen;
hence, the potential of a substance to attract hydrogen ions.
pH is a measure of the activity of hydrogen ions (H+) in a solution and
therefore its acidity or alkalinity. Though a pH value has no unit it is not
an arbitrary scale; the number arises from a definition based on the
activity of hydrogen ions in the solution.
2. What are the mathematical formulas of pH?
pH Formula is mathematically expressed as:

Calculating the Hydronium Ion Concentration from pH

The hydronium ion concentration can be found from the pH by the
reverse of the mathematical operation employed to find the pH.
[H3O+] = 10-pH or [H3O+] = antilog (- pH)

3. What is the relationship between hydrogen ion concentration,

hydroxyl ion concentration and the pH of a solution?

 As the H+ ion concerntration increases, the pH decreases.

As the OH- ion concerntration increases, the pH increases.
4. What is the significance of determining the pH of an antacid
preparation?
There are two other important considerations. First, the rate at which the
neutralization reaction occurs is very important. It should be relatively fast.
The second consideration is the fact that some of these antacids produce
carbon dioxide gas as one of the products of the neutralization reaction. In
this case, the reaction must occur quickly enough to relieve pain, but slowly
enough to allow the gas to dissipate and not build up in one's system.
5. What is the USP requirement for the pH of different antacid
preparation?
Antacid ingredients:
The minimum recommended dosage must provide a minimum acid
neutralising capacity (ANC) of 5 mEq and result in a pH of 3.5 or greater at
the end of the initial ten minute period as measured by the procedure
outllined in the United States Pharamacopeia XXII/National Formulary XVII.
Evidence that a product meets this standard must be available on request.

INSTRUMENTAL METHOD

#11

1. Why should the temperature of the sample be controlled during the

refractive index measurements?
Because it control improves the reliability of the results by removing
inconsistencies such as correction factors and rounding errors from the
process.
2. What is the significance of the refractive index measurement of
pharmaceutical substances?
The significance is it can be used as an aid in (1) identifying a pure
substance, (2) establishing the purity of some substances, (3) determining
the concentrations of some simple solutions (i.e., alcohol solutions, sugar
solutions [percent of sugar in syrup]), and (4) quickly determining the
uniformity of final compounded preparations, once a refractometric standard
has been established. RI (refractometry) is also used as a general,
nonspecific, method of detection in high-performance liquid chromatography
(HPLC). Refractometry is a basic and simple technique that can be used for
both qualitative and quantitative analysis.
3. Discuss the principle involved in the analysis
Measurement of RI of unknown substance by measuring angle of refraction
made when the substance is brought into contact with the medium (prism) of
a known refractive index
4. What are the different types of refractometers. Describe each

INSTRUMENTAL METHOD

#12

1. Define complete disintegration

Complete disintegration is defined as that state in which any residue of the
unit, except fragments of insoluble coating or capsule shell, remaining on the
screen of the test apparatus or adhering to the lower surface of the discs, if
used, is a soft mass having no palpably firm core.
2. What are the different parts of the disintegration apparatus
The apparatus consists of a basket-rack assembly, a 1000 mL, low-form
beaker, 138160 mm in height and having an inside diameter of 97115 mm
for the immersion fluid, a thermostatic arrangement for heating the fluid
between 35 C and 39 C and a device for raising and lowering the
basket in the immersion fluid at a constant frequency rate between 29 and
32 cycles per minute, through a distance of not less than 53 mm and not
more than 57 mm. The volume of the fluid in the vessel is such that at the
highest point of the upward stroke the wire mesh remains at least 15 mm
below the surface of the fluid and descends to not less than 25 mm from the
bottom of the vessel on the downward stroke. At no time should the top of
the basketrack assembly become submerged. The time required for the
upward stroke is equal to the time required for the downward stroke and the
change in stroke direction is a smooth transition rather than an abrupt
reversal of motion. The basket-rack assembly moves vertically along its axis.
There is no appreciable horizontal motion or movement of the axis from the
vertical.
3. What is the significance of this test for uncoated tablets
The rationale for using disintegration test is the fact that as the tablet
breakdown into small granules, it offers a greater surface area to the
dissolving media and thus must be related to the availability of the drug in
the body. But this test offers no assurance that the resultant particles will
release the drug in solution at appropriate rate, thats why the dissolution
test has been developed
4. Would disintegration test be the same for coated tablets, capsules
and enteric coated tablets. Why
Yes, Enteric coated tablets are similarly tested . Except that the tablets are
tested in simulated gastric fluid for one hour , after which no sign of
disintegration , cracking or softening must be seen. They are immersed in
simulated intestinal fluid for the time specified in the monograph, during
which time the tablets disintegrate completely for a positive test.
5. What factors affect the disintegration of tablets and capsules
1. Content : especially the quantity and quality of the disintegrant and
lubricant (mixing condition and time of addition of lubricant), the lubricant
increase the disintegration time by decreasing the wettability of the tablets
due to its hydrophobicity.
2. Hardness: amount of binder , compression force.
3. Design of granulation procedure which will affect the physical properties of
the granules.

INSTRUMENTAL METHOD

#13

1. In the dissolution test for tablets, why is it necessary to use the

paddle instead of the cylindrical basket?
Easy to use
Robust
pH change possible
Can be easily automated which is important for routine investigations
2. What are the important considerations in performing a dissolution
test?
Distilled water is the preferred medium
If deemed necessary because of the nature of the drug buffered
aqueous solution having a pH between 4-8 should be used. Where its
can be justified, dilute acid may be selected.
No enzymes should be incorporated
Quantity should be not less than three times that required to form a
saturated solution of the drug substance present in the dosage unit.
3. Define dissolution testing and give the significance of the test?
Dissolution in the broad sense is more than simple measurement of the
rate of solubility. It may be more accurately described as a physical
test to predict drug delivery to a target area in the proper amount at
the right time.
Significance
1. To meet legal requirements for compential drugs
2. As quality control tool for drug product manufacturing.
3. As dosage formulations optimization tool.
4. For stability- bioavailability of drug over shelf-life

INSTRUMENTAL METHOD

#14

1. Define friability test

Also called as Drop Test or Abrasion Test
It is a tablet property related to hardness.
It is the ability to withstand abrasion in packaging, handling and
shipping.
It is the tendency of tablets to powder, chip, or fragment
Attrition Resistance Test
Friability is the tendency for a tablet to chip, crumble or break
following compression. This tendency is normally confined to uncoated
tablets and surfaces during handling or subsequent storage
2. What is the significance of friability testing?
The strength of a tablet plays a very important role in its marketing and
dissolution. The mechanical strength of tablet or granules can be determined
by its hardness and through friability test.Measuring the hardness of a tablet
is not a reliable indicator for tablet strength as some formulations when
compressed into very hard tablets tend to 'cap' or lose their crown portions
on attrition. Such tablets tend to powder, chip and fragment.
3. What are the factors affecting friability of the tablet?

Punches that are in poor condition or worn at their surface edges,

resulting in whiskering at the tablet edge and show higher than
normal friability values.
internal factors like the moisture content of tablet granules and
finished tablets. Moisture at low and acceptable level acts as a binder
4. Describe the drum part of the friabilator
The drum has an inside diameter of 287mm and is about 38mm in depth,
made of a transparent synthetic polymer with polished internal surface. A set
of pre weighed tablets [if one tablet weigh 650mg or less then approx 6.5g of
total weight should be taken and for more than 650mg/tablet weight, 10
tablets should be taken] (3) are placed in the plastic chamber revolving at 2425rpm for 4 min. The tablets are subjected to combined effects of abrasion
and shock. The tablets are dropped at a distance of six inches on each
revolution.If the tablet size or shape becomes irregular adjust the drum so
that base forms an angle of about 10 degrees with bench top and the tablets
fall freely when drum is rotated.