Quality control of capsulesQuality control of capsules

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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.

-Capsules are usually intended to be administered orally by swallowing them whole. Occasionally, capsules may be administered rectally or vaginally.

Visual examination of capsulesVisual 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 capsulesSome 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 .

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.

Compendial Requirements for Capsules

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 averageweight by more than the percentage deviation shown in the table below, and none deviates by more than twice that percentage.

Average Weight ofAverage Weight of

Capsule ContentCapsule Content

Percentage deviationPercentage deviation

Less than 300 mgLess than 300 mg1010

300300 mg or moremg or more7.57.5

3 -Disintegration:

The disintegration test determines whether tablets or capsulesdisintegrate 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 ina 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 fromthe 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 apparatusofficial in the USP.

- The capsule is placed in a basket formed from 40-mesh stainlesssteel 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 vesseland 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 color-revealing 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 formsSemi solid dosage forms Semisolid dosage forms are products of semisolid consistency Semisolid dosage forms are products of semisolid consistency and applied to skin or mucous membranes for therapeutic or and applied to skin or mucous membranes for therapeutic or protective action or cosmetic functionprotective action or cosmetic function..

1 .CREAMS- : They are viscous semisolid emulsion system with opaque appearance compared with the translucent ointments. Consistency and rheological charactersdepend 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. pertrolatumSince they are mostly of greasy nature so they stain cloths, are generally poorsolvent for most drugs, and usually decrease the drug delivery capabilities of the system.

IDEAL PROPERTIES OF SEMISOLID DOSAGE FORMS

1.PHYSICAL PROPERTIES: -

a) Smooth textureb) Elegant in appearancec) Non dehydratingd) Non grittye) Non greasy and non stainingf) Non hygroscopic

2 .PHYSIOLOGICAL PROPERTIES: -

a) Non irritatingb) Do not alter membrane / skin functioningc) Miscible with skin secretiond) Have low sensitization effect

3. APPLICATION PROPERTIES: -

a) Easily applicable with efficient drug releaseb) High aqueous washability

Evaluation of ointment and cream Evaluation of ointment and cream preparationspreparations

pHpH Drug content Drug content ViscosityViscosity SpreadabilitySpreadability In vitroIn vitro release study release study

Measurement of pHMeasurement of pH

The pH of various topical preparations was determined by using The pH of various topical preparations was determined by using digital pH meter. One gram of the topical preparation was digital pH meter. One gram of the topical preparation was dissolved in 100 ml of distilled water and stored for 2 hrs. The dissolved in 100 ml of distilled water and stored for 2 hrs. The measurement of pH was done in triplicate and average values are measurement of pH was done in triplicate and average values are calculated. calculated. N.B For ointments it is difficult to check the pH because they are N.B For ointments it is difficult to check the pH because they are oily.oily.

Drug content :Drug content :

Stock solution is prepared and aliquots of different concentration Stock solution is prepared and aliquots of different concentration were prepared by suitable dilutions after filtering the stock were prepared by suitable dilutions after filtering the stock solution and the absorbance is measured and the drug content was solution and the absorbance is measured and the drug content was calculated using the equation, which was obtained by linear calculated using the equation, which was obtained by linear

regression analysis of calibration curveregression analysis of calibration curve..

Viscosity study :Viscosity study :

The measurement of viscosity of the prepared topical preparation The measurement of viscosity of the prepared topical preparation was done with Brookfield viscometer. The preparations are was done with Brookfield viscometer. The preparations are rotated at different speeds and shear rates. At each speed the rotated at different speeds and shear rates. At each speed the corresponding dial reading is notedcorresponding dial reading is noted..

Minimum fill:Minimum fill:

It is the determination of the net weight of the contents of filled containers to 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 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 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 removal of the container contents. Thoroughly cleanse and dry the outside of the containers by a suitable means, and weigh individually.the containers by a suitable means, and weigh individually.

Quantitatively remove the contents from each container, cutting the latter open 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 washing with a suitable solvent, if necessary, taking care to retain the closure and other parts of each container.and other parts of each container.

Dry, and again weigh each empty container together with its corresponding 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 parts. The difference between the two weight is the net weight of the contents of the container.the container.

The average net content of 10 containers is not less than the labeled amount, and 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 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 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 gwhere the labeled amount is more than 60 g but not more than 150 g..

Spreadability :Spreadability :

It is the term expressed to denote the extent of area to which the It is the term expressed to denote the extent of area to which the preparation readily spreads on application to skin or affected area.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:The in vitro release test:

This test is done to ensure within lot and lot-to-lot uniformity. In This test is done to ensure within lot and lot-to-lot uniformity. In vitro release tests include diffusion cell studies to determine the vitro release tests include diffusion cell studies to determine the drugs release profile from the semisolid product. drugs release profile from the semisolid product.

This test is carried out in Franz diffusion cell for studying This test is carried out in Franz diffusion cell for studying dissoluion release through a cellophane membrane.dissoluion release through a cellophane membrane. Certain weight of the preparation for example 0.5 g is taken in Certain weight of the preparation for example 0.5 g is taken in cellophane membrane and the diffusion studies were carried at 37±1 cellophane membrane and the diffusion studies were carried at 37±1 degree, using 250 ml of phosphate buffer pH 7.4 as dissolution degree, using 250 ml of phosphate buffer pH 7.4 as dissolution medium.medium. Samples are withdrawn periodically and the samples analysed for Samples are withdrawn periodically and the samples analysed for

drug contentdrug content . .

Packaging, storage, and labeling:Packaging, storage, and labeling:

●● Ointments and other semisolid preparations are packaged either Ointments and other semisolid preparations are packaged either in large-mouth ointment jars or in metal or plastic tubes. Semisolid in large-mouth ointment jars or in metal or plastic tubes. Semisolid preparations must be stored in well-closed containers to protect preparations must be stored in well-closed containers to protect against contamination and in a cool place to protect against against contamination and in a cool place to protect against product separation in heat.product separation in heat.

● When required, light-sensitive preparations are packaged in ● When required, light-sensitive preparations are packaged in opaque or light-resistant containers.opaque or light-resistant containers.

●● The USP directs that the labeling for certain ointments and The USP directs that the labeling for certain ointments and creams include the type of base used (e.g., water soluble or water creams include the type of base used (e.g., water soluble or water insoluble)insoluble)