IN PROCESS QUALITY CONTROL: A REVIEW

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IN PROCESS QUALITY CONTROL: A REVIEW

The development of a drug product is a lengthy process involving drug discovery, laboratory testing, animal studies, clinical trials and regulatory registration. To further enhance the effectiveness and safety of the drug product after approval, many regulatory agencies such as the United States Food and Drug Administration (FDA) also require that the drug product be tested for its identity, strength, quality, purity and stability before it can be released for use. For this reason, pharmaceutical validation and process controls are important in spite of the problems that may been countered. Process controls include raw materials inspection, in-process controls and target so for final product. IPQC stands for in process quality control. These are checks that are carried out before the manufacturing process is completed. The function of of in-process controls is monitoring and if necessary adaption of the manufacturing process in order to comply with the specifications .this may include control of equipment and environment too. Inprocess materials should be tested for identity, strength, quality and purity as appropriate and approved or rejected by the quality control unit during the production process. Rejected in-process materials should be identified and controlled under a quarantine system designed to prevent their use in manufacturing

DEFINITION OF IPQC

IPQC stands for IN PROCESS QUALITY CONTROL . These are checks that are carried out before the manufacturing process is completed. The function of in-process controls is monitoring and if necessary adaption of the manufacturing process in order to comply with the specifications .this may include control of equipment and environment too. In-process materials should be tested for identity, strength, quality and purity as appropriate and approved or rejected by the quality control unit during the production process. Rejected in-process materials should be identified and controlled under a quarantine system designed to prevent their use in manufacturing .Written procedure should be established and followed that describe the inprocess controls and tests as specified:

  • Tablet or capsule weight variation.
  • Disintegration time.
  • Content uniformity and homogenecity.
  • Dissolution time and rate.
  • Clarity,Completeness or pH of solutions.

IPQC TESTS FOR VARIOUS DOSAGE FORMS:

Tablets:

  1. Drug contents determination.
  2. Moisture contents of granules.
  3. Assay of active ingredients.
  4. Weight variation of uncoated tablets.
  5. Hardness test.
  6. Disintegration test.

Drug Content Determination

A physically sound tablet may not produce the desired effects. To evaluate a tablet potential for efficiacy, the amount of drug per tablet needs to be monitored from tablet to tablet and batch to batch, and a measure of the tablets ability to release the drug needs to be ascertained.

Moisture Content of granules

Granules should possess sufficient strength to withstand normal handling and mixing processes without breaking down and producing large amounts of fine powder. On the other hand, some size reduction during compaction into tablets is desirable to expose the areas of clean surface necessary for optimum bonding to take place so moisture content is the very important factor for producing god pharmaceutical product.

Assay of active ingredient

In a tablet an active ingredient is present which is called active pharmaceutical ingredient (A.P.I).So to prepare the tablet assay has to be done to produce good finished product.

Hardness test

The monitoring of tablet hardness is especially important for drug products that possess real or potential bioavailability problems that are sensitive to altered dissolution release profiles as a function of the compressive force employed .One of the earliest testers to evaluate tablet hardness was the Monsanto hardness tester to evaluate tablet hardness tester.

Disintegration test

A generally accepted maximum is that drug to be readily available to the body, it must be in solution. For most tablets, the first important step towards solution is break down of the tablet into smaller particles or granules, a process known as disintegration .The U.S.P device to test disintegration uses 6 glass tubes that are 3 inches long, open at the top, and held against a 10 mesh screen at the bottom end of the basket rack assembly. To test for disintegration time, one tablet is placed in each tube , and the basket rack is positioned in a 1-L beaker of water ,simulated gastric fluid and at 37°-+2°c ,such that tablet remains 2.5cm below the surface of the liquid on their upward movement and descend not closer than 2.5cm from the bottom of the beaker. A standard motor driven device is used to move the basket assembly containing the tablets up and down through distance of 5 to 6cm at a frequency of 28 to 32 cycles per minute.

I.P.Q.C TEST FOR SYRUPS AND SUSPENSION

  1. Drug contents determination.
  2. Assay of active ingredients.
  3. pH.
  4. Weight per ml.
  5. particle size

Drug content determination

Determination of drug content in suspension and syrups are important because their concentration has to be sufficient itself that it produce the pharmacological action. A suspension is much prescribed to pediatrics so their concentration has to be sufficient not to less not to large.

Assay of active ingredient

Active ingredient means pure drug present in the product .An assay of active ingredient must be done because it is the only which is responsible for pharmacological action and in syrups and suspension a small and fine particles are included in syrups and suspension

pH of the product

pH affects the stability of the product so before filling and after filling of suspension and syrups pH has to be checked out for consistency of the product.

Particle size

In suspension and syrups a solute particles is dispersed in a suitable solvent so particle size becomes the important factor for the suitability of the product and all the particles has to be of same size and shape for proper dispersing in the solvent.

I.P.Q.C TEST FOR SEMI- SOLIDS

  1. Drug contents determination.
  2. Assay of active ingredients.
  3. Uniformity and homogeneity test.
  4. Viscosity and specific gravity test.
  5. Filling test.

Drug content determination

As all have discussed earlier drug content becomes important factor for active pharmaceutical product. Drug content has to be of very suitable ratio that it can give the pharmacological action.

Homogenecity test

The semi-solid preparations require further treatment are transferred or pumped to the proper homogenizer, the selection of which is governed by the degree and rate of shear stress required.

Viscosity and Specific gravity test

Once the desired semi-solid preparation have been chosen, a consistency that provides the desired stability and has appropriate flow characterstics must be attained. For emulsion it is routinely observed that the building up of viscosity in a freshly prepared emulsion requires some time. The is recommended, therefore that newly formulation emulsion be allowed to rest undisturbed for 24 to 48 hours before it is determined whether its rheologic properties correspond to those that are required. The viscosity of emulsions responds to changes in composition in accordance with the following generalizations.

  • There is a linear relationship between emulsion viscosity and viscosity of continous phase.
  • The greater the volume of the internal phase, the greater is the apparent viscosity.
  • To control emulsion viscosity, three interacting effects must be balanced by the formulator.
  • The viscosity of o/w and w/o emulsions can be increased by the reducing the particle size of
  • the dispersed phase.
  • Emulsion stability is improved by a reduction in particle in particle size.
  • Flocculation or clumping which tends to structure the internal phase ,can be stabilizing
  • effect, it increases the viscosity .

I.P.Q.C TEST FOR INJECTABLES

  1.  Drug contents determination.
  2.  Clarity test.
  3.  pH.
  4.  Pyrogen test.
  5.  Stability test.
  6.  Leakage test.
  7.  Check up of particulate matters.

Pyrogen test

The presence of pyrogenic substance in parentrals is determined by a qualitative biologic test based on the fever response of the rabbits. Rabbits are used as test animal because they show a physiologic response to pyrogens similar to that of human beings. If a pyrogenic substance is injected into the vein of a rabbit, an elevation of temperature occurs in a period of three hours.

Sterility test

All products labeled “sterile” must pass through sterility test, having been subjected to an effective process of sterilization. The traditional concept of sterilization is the absolute condition of total elimination of all the microorganisms. With a terminal methods of sterilization of a parenteral product, particularly steam under pressure, a probability of no more than one sterile unit in a million is readily achievable. The term aseptic indicates a controlled process in which the level of microbial contamination is reduced to the degree that microorganisms can be excluded from a product during processing. It describes apparently sterile state.

Leaking test

Ampules are intended to provide hermetically sealed container for a single dose of a product, thereby completely barring any interchange between the contents of the sealed ampule and its environment. Should capillary pores or tiny cracks be present, microorganisms or other dangerous contaminants may enter the ampule or the contents may leak to the outside and spoil the appearance of the package. Changes in temperature during storage cause expansion and contraction of the ampule and contents, thereby accentuating interchange if an opening exists. Leakers usually detected by producing a negative pressure with an incompletely sealed ampule, usually in a vaccum chamber, while the ampule is entirely submerged in a deeply coloured dye solution ,usually 0.5 to 0.1% methylene blue. Subsuequent atmospheric pressure then causes dye to penetrate an opening, being visible after the ampule has been washed externally to clear it of dye. The vaccum (27 inches Hg or more) should be sharply released after30 min. Only a tiny drop of dye may penetrate a small opening. Vials and bottles are not subjected to such a leaker test because the rubber closure is not rigid; however, bottles are often sealed while a vacuum is being pulled so that the bottle remains evacuated during its shelf life.

Clarity test

Clarity is the relative term, the meaning of which is markedly affected by the subjective evaluation of the observer. Unquestionly a clean solution having a high polish conveys to the observer that the product is of exceptional quality and purity .It is practically impossible, however, to prepare a lot of a sterile product so that every unit of that lot is perfectly free from visible particulate matter, that is , from particles that are 30 to 40 micrometer and larger in size. Consequently it is the responsibility of the quality control department to detect and discard individual containers of a product that the ultimate user would consider to be unclean. This clarity test is performed in industry by visual inspection machine by the light baffles against reflection into the eyes, and views against a black and white background, with the contents set in motion with a swirling action

Stability

To enhance the assurance of successful manufacturing operations, all process steps must be carefully reduced to writing after being shown to be effective. These process steps are often called standard operating procedures(SOPs).No extemporaneous changes are permitted to be made in these procedures; any change must go through the same approval steps as the original written SOP. Further external records must be kept to give assurance at the end of the production process that all steps have been performed as prescribed. Such in-process control is essential to assuring the quality of the product, since these assurances are even more significant than those from product release testing.

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