Transcript quality control lect..

Quality control of capsules
Definition:
- Capsules are solid dosage forms in which the medication contained
within gelatin shells. The medication may be a powder, a liquid or a
semisolid mass.
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- Capsules are usually intended to be administered orally by swallowing
them whole. Occasionally, capsules may be administered rectally or
vaginally.
Visual examination of capsules
● Capsules within one lot shall be of the same color, transparency,
size and shape.
● If one capsule bears the identifying markings, all capsules shall bear
the identical marking.
● Any coloring material employed in the capsules shall be uniformily
and homogenously distributed.
● Capsules shall show no evidence of defects.
Some of the major defects in capsules
 Capsules not free from cracks, breaks, pinholes or splits where
leakage of contents may occur (fracture in the surface of the capsule).
 Capsules empty.
 Capsule fill not free from foreign matter (foreign materials contained
in the capsule and not visible from the surface).
 Capsules not intact (i.e. cap is separated from the body).
 Non-uniformity of color.
 Surface spots (contamination)
● Defined particles which are embedded in or on the
surface of the capsule.
● Defined particles which adhere to the surface but
can be wiped or blown off of the surface.
Compendial Requirements for Capsules
1. Added Substances
a. Harmless in the quantities used.
b. Do not exceed the minimum amounts required to provide
their intended effect.
c. Do not impair the product’s therapeutic efficacy,
bioavailability or safety.
d. Do not interfere with requisite compendial assays
and test.
2. Containers for dispensing
Containers depending on the item tight, well closed and light
resistant.
Evaluation of commercial capsules
1- content uniformity:
- 30 capsules are selected and 10 of these are assayed individually.
- At least 9 of these contain 85 – 115 % of drug and none contain below
75-125% of drug.
- If 1 to 3 of them fall outside of 85 – 115% limits, the remaining 20
capsules are individually assayed and the requirements are met if no few
than 27 contain 85 – 115 % of drug and none contain less than 75 – 125
% of drug.
2- Weight Uniformity :
- This test applies to all types of capsules and it is to be done on 20
capsules.
Method: ( Hard gelatin capsules)
1- Weigh an intact capsule.
2- Open the capsule without losing any part of the shell and remove the
contents as completely as possible.
3- Weigh the shell.
4- The weight of the contents is the difference between the weighing.
5- Repeat the procedure with a further 19 capsules selected at random.
6- Determine the average weight.
Weight Variation
Soft Gelatin:
The gross weight of 10 intact capsules is determined individually. Then
each capsule is cut open and the contents removed by washing with
suitable solvent. The solvent is allowed to evaporate at room
temperature over about 30 minutes. The individual shells are weighed
and net contents calculated.
Limit:
Not more than two of the individual weights deviate from the average
weight by more than the percentage deviation shown in the table below,
and none deviates by more than twice that percentage.
Average Weight of
Capsule Content
Less than 300 mg
Percentage deviation
300 mg or more
7.5
10
3- Disintegration:
The disintegration test determines whether tablets or capsules
disintegrate within a prescribed time when placed in a liquid
medium under the prescribed experimental conditions.
Method:
According to the B.P. and applies to hard and soft capsules.
1- Introduce one capsule into each tube and suspend the apparatus in
a beaker containing 600 ml water at 37 °C.
If hard capsules float on the surface of the water, the discs may be
added.
2- Operate the apparatus for 30 minutes; remove the assembly from
the liquid.
3-The capsules pass the test if
– No residue remains on the screen of the apparatus or,
– If a residue remains, it consists of fragments of shell or,
– Is a soft mass with no palpable core.
– If the disc is used, any residue remaining on its lower surface should
only consist of fragments of shell.
4- Dissolution:
- The dissolution test is carried out using the dissolution apparatus
official in the USP.
- The capsule is placed in a basket formed from 40-mesh stainless
steel fabric.
- A stirrer shaft is attached to the basket, and the basket is immersed in
the dissolution medium and caused to rotate at a specified speed.
- The dissolution medium is held in a covered 1000 ml glass vessel
and maintained at 37°C ± 0.5°C by means of a suitable constant
temperature water bath.
- The stirrer speed and type of dissolution medium are specified in the
individual monograph.
5. Content Labeling Requirement
 All official capsules must be labeled to express the quantity of active
ingredient in each dosage unit.
6. Stability Testing
 To determine the appropriate conditions for storage and the
product’s anticipated shelf life.
7. Moisture Permeation Test
 determined by packaging the dosage unit together with a colorrevealing dessicant pellet, exposing the packaged unit to known relative
humidity over a specified time, observing the dessicant pellet for color
change ( indicating absorption of moisture) and comparing the pretest
and posttest weight of the package unit.
Semi solid dosage forms
 Semisolid dosage forms are products of semisolid consistency
and applied to skin or mucous membranes for therapeutic or
protective action or cosmetic function.
1. CREAMS : They are viscous semisolid emulsion system with opaque appearance compared
with the translucent ointments. Consistency and rheological characters
depend on whether the cream is w/o or o/w.
Properly designed O/W creams are elegant drug delivery system, pleasing in both
appearance and feel after application.
O/W creams are non greasy and are rinsable.
They are good for most topical purposes.
2. OINTMENTS:They are soft hydrocarbon based semisolid preparations, e.g. pertrolatum
Since they are mostly of greasy nature so they stain cloths, are generally poor
solvent for most drugs, and usually decrease the drug delivery capabilities of the
system.
IDEAL PROPERTIES OF SEMISOLID DOSAGE
FORMS
1.PHYSICAL PROPERTIES: a) Smooth texture
b) Elegant in appearance
c) Non dehydrating
d) Non gritty
e) Non greasy and non staining
f) Non hygroscopic
2. PHYSIOLOGICAL PROPERTIES: a) Non irritating
b) Do not alter membrane / skin functioning
c) Miscible with skin secretion
d) Have low sensitization effect
3. APPLICATION PROPERTIES: a) Easily applicable with efficient drug release
b) High aqueous washability
Evaluation of ointment and cream
preparations
pH
 Drug content
Viscosity
Spreadability
 In vitro release study
Measurement of pH
The pH of various topical preparations was determined by using
digital pH meter. One gram of the topical preparation was
dissolved in 100 ml of distilled water and stored for 2 hrs. The
measurement of pH was done in triplicate and average values are
calculated.
N.B For ointments it is difficult to check the pH because they are
oily.
Drug content :
Stock solution is prepared and aliquots of different concentration
were prepared by suitable dilutions after filtering the stock solution
and the absorbance is measured and the drug content was
calculated using the equation, which was obtained by linear
regression analysis of calibration curve.
Viscosity study :
The measurement of viscosity of the prepared topical preparation
was done with Brookfield viscometer. The preparations are rotated
at different speeds and shear rates. At each speed the
corresponding dial reading is noted.
Minimum fill:
 It is the determination of the net weight of the contents of filled containers to
ensure proper contents compared to the labeled amount. Select a sample of 10
filled containers, and remove any labeling that might be altered in weight during
the removal of the container contents. Thoroughly cleanse and dry the outside of
the containers by a suitable means, and weigh individually.
 Quantitatively remove the contents from each container, cutting the latter open
and washing with a suitable solvent, if necessary, taking care to retain the closure
and other parts of each container.
 Dry, and again weigh each empty container together with its corresponding
parts. The difference between the two weight is the net weight of the contents of
the container.
 The average net content of 10 containers is not less than the labeled amount,
and the net content of single container is not less than 90% of the labeled amount
where the labeled amount 60 g or less. Not less than 95% of the labeled amount
where the labeled amount is more than 60 g but not more than 150 g.
Spreadability :
 It is the term expressed to denote the extent of area to which the
preparation readily spreads on application to skin or affected area.
 The therapeutic efficiency of the formulation also depends upon its
spreading value. Hence, determination of spreadability is very
important in evaluating topical application characteristics.
 For the determination of spreadability, excess of sample was
applied in between two glass slides and was compressed to uniform
thickness by placing weight load for certain time. Thereafter the top
plate was subjected to pull with the help of string attached to the hook.
The time in which the upper glass slide moves the lower plate to cover
a distance of 10 cm is noted. Lesser the time taken for separation of
the two slides better the spreadability.
The in vitro release test:
 This test is done to ensure within lot and lot-to-lot uniformity. In
vitro release tests include diffusion cell studies to determine the
drugs release profile from the semisolid product.
 This test is carried out in Franz diffusion cell for studying
dissoluion release through a cellophane membrane.
 Certain weight of the preparation for example 0.5 g is taken in
cellophane membrane and the diffusion studies were carried at 37±1
degree, using 250 ml of phosphate buffer pH 7.4 as dissolution
medium.
 Samples are withdrawn periodically and the samples analysed for
drug content.
Packaging, storage, and labeling:
● Ointments and other semisolid preparations are packaged either
in large-mouth ointment jars or in metal or plastic tubes. Semisolid
preparations must be stored in well-closed containers to protect
against contamination and in a cool place to protect against
product separation in heat.
● When required, light-sensitive preparations are packaged in
opaque or light-resistant containers.
● The USP directs that the labeling for certain ointments and
creams include the type of base used (e.g., water soluble or water
insoluble)