quality control of parenterals

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By: parneyshruthi (30 month(s) ago)

hello sir i liked your qc on parenterals ppt please allow me to download

By: parneyshruthi (30 month(s) ago)

Hello i liked your presentation please allow me to download it please sir please

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QUALITY CONTROL OF PARENTERALS, SUPPOSITORIES, CREAMS & OINTMENT, SUSTAIN RELEASE DOSAGE FORM Facilitated by, Sudha mallapur Asst.Professor Presented by, Masood Mohammad, Dept. of pharmaceutical analysis, EAST WEST COLLEGE OF PHARMACY

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INTRODUCTION The quality of finished product depends on quality assurance and quality control Quality assurance : it relates to the studies made and the plans developed for assuring quality of product prospectively. Quality control : QC is a concept which strives to produce a perfect product by series of measures designed to prevent & eliminate errors at different stages of production.

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QUALITY CONTROL OF PARENTERALS : There are mainly five Quality Control test for the PARENTERALS are performed. STERILITY TEST PYROGEN TEST PARTICULATE EVALUATION LEAKER TEST UNIFORMITY OF CONTENT

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STERILITY TEST All lots of injections in their final containers must be tested for sterility. The USP prescribes the requirements for this test for official injections. The FDA uses these requirements as a guide for testing unofficial sterile products. The primary official test is performed by means of filtration, but direct transfer is used if membrane filtration is unsuita ble .

Methods for testing:

Methods for testing Membrane filteration method Direct inoculation method Media suitable for sterility tests are: Fluid thioglycollate medium Soya-bean casein digest medium

Membrane filtration method:

Membrane filtration method Parenteral preparation ( 5cmdm,0.45mi pore ) membrane filter (sterile and free from microorganisms ) Wash the filters with fluids to remove inhibitory properties, cutting the membranes aseptically into equal parts and transferring one of the parts to each type of culture medium used. The media are then incubeted under prescribed conditions.

DIRECT INOCULATION METHOD:

DIRECT INOCULATION METHOD Parenteral preparations . Culture medium If no growth the test will be positiv e

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(B) PYROGEN TEST Evaluates the presence of pyrogens in parenteral preparations. The Bacterial Endotoxins Test (BET) is an in vitro test based on the formation of a gel or the development of color in the presence of bacterial endotoxins and the lysate of the amebo cytes of the horseshoe crab (Limulus polyphemus). The Limulus Amebocyte Lysate (LAL) test, as it also is called, is a bio chemical test.

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LAL test Principle : The addition of solution containing endotoxins to a solution of lysate produce turbidity, precipitation or gel formation of the mixture. The rate of reaction depends on the concentration of the endotoxin. The reaction requires the presence of contain bivalent cations such as preclotting enzyme system and clottable protein all of which are provided by lysate. The quantities of endotoxins are expressed as endotoxins units . Reagents used:- Lysate Water 0.1m HCl 0.1m NaOH Trichloride buffer of pH 7.4

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Procedure: Carry out the following procedure in duplicate receptacles. Into each test tubes dispense a volume appropriate to the chosen receptacle of negative control, standard endotoxin concentration or positive control, test solution. Add to each receptacles and equal volume of the appropriately constituted lysate . place in an incubating device at 37 ± 1 0 C undisturbed and avoiding lose of water by evaporation, for 60 ± 2 minutes Compare the result.

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Interpretation of result: The substance or preparation being examined complies with pyrogen test if the positive product control is positive and negative control are negative. The test is invalid if the positive control is negative or if any negative control is positive. The LAL test is cheaper, quicker and more accurate than the other test.

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(C) PARTICULATE EVALUATION: It has been shown that particles of lint, rubber, insoluble chemicals, and other foreign matter can produce emboli in the vital organs of animals and human beings. The USP specifies that good manufacturing practice (GMP) requires that each final container of an injection be subjected individually to a visual inspection and that containers in which visible particles can be seen should be discarded. Therefore, all of the product units from a production line currently are being inspected individually by human inspectors under a good light, baffled against reflection into the eye and against a black-and-white background.

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The USP has identified two test methods. The first test to be used is the light obscuration test , which uses an electronic instrument designed to count and measure the size of particles by means of a shadow cast by the particle as it passes through a high- intensity light beam. If the injection formulation is not a clear, colorless solution , it exceeds the limits specified for the light obscuration test, it is to be subjected to the microscopic count test.

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(D) LEAKER TEST Ampoules that have been sealed by fusion must be subjected to a test to determine whether or not a passageway remains to the outside If all or a part of the contents may leak to the outside and spoil the package or microorganisms or other contaminants may enter. This test usually is performed by producing a negative pressure within an incompletely sealed ampoule while the ampoule is submerged entirely in a deeply colored dye solution. Most often, approximately 1% methylene blue solution is employed. .

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After carefully rinsing the dye solution from the outside, color from the dye will be visible within a leaker (E)UNIFORMITY OF CONTENT Determine the content of active ingredient of each of 10 containers taken at random using the method given in the monograph or by any other suitable analytical method. The preparation being examined complies the test if the individual values thus obtained are all between 85 and 115 % of the average value.

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QUALITY CONTROL OF SUPPOSITORIES: Testing of Suppositories: Finished suppositories are routinely inspected for appearance, and after being sliced length wise & for uniformity of the mix. They are assayed for active ingredients to ensure that they individually conform to labeled content. There are mainly five Quality Control test for the suppositories. (A) Uniformity of content. (B) Uniformity of weight. (C) Breaking Test. (D) Melting Range Test. (E) Liquefaction or Softening Time Tests

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Weight Uniformity: - Weigh 20 suppositories individually. w1, w2, w3….w20 - Weigh all the suppositories together = W. - Calculate the average weight = W/20. Limit: Not more than 2 suppositories differ from the average weight by more than 5%, and no suppository differs from the average weight by more than 10%.

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(C) Breaking Test The breaking test is designed as a method for measuring the fragility or brittleness of suppositories. The apparatus used for the test consists of a double-wall chamber in which the test suppository is placed. Water at 37°C is pumped through the double walls of the chamber and the suppository contained in the dry inner chamber supports a disc to which a rod is attached.

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The other end of the rod consists of another disc to which weights are applied. The test is conducted by placing 600 g on the platform. At 1-mm intervals, 200 g weights are added and the weight at which the suppository collapses is the breaking point, or the force that determines the fragility or brittleness characteristics of the suppository. Differently shaped suppositories have different breaking points.

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(D) Melting Range Test This test is also called the macro melting range test and is a measure of the time it takes for the entire suppository to melt when immersed in -a constant-temperature (37°C) water bath. The apparatus commonly used for measuring the melting range of the entire suppository is a USP Tablet Disintegration Apparatus. The suppository is completely immersed in the constant water bath, and the time for the entire suppository to melt or disperse in the surrounding water is measured.

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(E) Liquefaction or Softening Time Tests of Rectal Suppositories It consists of a U-tube partially submersed in a constant-temperature water. A constriction on one side holds the suppository in place in the tube. A glass rod is placed on top of the suppository, and the time for the rod to pass through to the constriction is recorded as the “ softening time .” This can be carried out at various temperatures from 35.5 to 37°C, as a quality control check and can also be studied as a measure of physical stability over time. A water bath with both cooling and heating elements should be used to assure control within 0.1°C. The “softening test” measures the liquefaction time of rectal suppositories in an apparatus that simulates in vivo conditions.

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Water at 37°C is circulated through the condenser at such a rate that the lower half of the cellophane tube collapses and the upper half gapes. The hydrostatic pressure of the water in the apparatus is approximately zero when the tube starts to collapse. When the water temperature is stabilized at 37°C, the suppository is dropped into it so that it sits at the level shown in Figure and the time is measured for the suppository to melt completely in the tube.

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QUALITY CONTROL OF SUSTAIN RELEASE DOSAGE FORM Properly designed in vitro tests for drug release serve two important functions: Data from such tests are required as a guide to formulation during the development stage, prior to clinical testing. In vitro testing is necessary to ensure batch-to-batch uniformity in the production of a proven dosage form Tests developed for the purpose of quality control are generally limited to USP dissolution testing methods; Using either the rotating basket The paddle The modified disintegration testing apparatus

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The methods used to measure drug release profiles should have the following characteristics. Analytic technique should be automated so that the complete drug release profile can be directly recorded. Allowance should be made for changing the release media from simulated gastric to simulated intestinal fluid at variable programmed time intervals to establish the effect of retention of the dosage form in gastric fluid as well as to approximate more closely the pH shifts that the dosage form is likely to encounter in vivo.

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3.The apparatus should be calibrated using a non disintegrating dissolution standard (e.g., salicylic acid com pacts). 4.Besides the USP dissolution testing apparatus including the rotating bottle, stationary basket/rotating filter, Sartorius absorption and solubility simulator, and column-type flow-through assembly. 5. The rotating bottle method was developed for evaluation of sustained release formulations. Samples are tested in 90-ml bottles containing 60 ml of fluid, which are rotated end over end in a 37 °C bath at 40 rpm.

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6.The Sartorius device includes an artificial lipid membrane, which separates the “dissolution” chamber from a simulated plasma compartment in which drug concentrations are measured. 7. The column flow-through apparatus possesses similar advantages since drug release is confined to a relatively small chamber by highly permeable membrane filters. This apparatus is flexible, well-defined, and meets all the necessary requirements for measurement of drug release profiles from sustained release dosage forms.

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QUALITY CONTROL OF CREAMS & OINTMENT ( A) Particle Size Number Analysis: Changes of the average particle size or of the size distribution of droplets are important parameters for evaluating emulsions. Particle size analysis may be carried out by a number of methods, each giving a somewhat different average for heterodisperse systems. For example, Microscopic measurements of the apparent diameter give an average value dependent on the number of particles of each size. .

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On the other hand, some Electronic counting devices measure particle volume, and since the volume of a sphere is give greater weight to larger particles when volume is converted to diameter. Such counting devices. e.g., the Coulter counter Light scattering and related reflectance relationships have been used for particle size determinations. Thus, the change of reflectance at wave length at which the colored internal phase partially absorbs the incident light has been found to be inversely proportional to a power of the particle diameter.

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( B) Uniformity of weight : OINTMENTS, CREAMS, PASTES, GARANULES & POWDER FOR ORAL LIQUIDS The following tests and specifications apply to oral dosage forms and preparations intended for topical use that are packaged in containers in which the labeled net quantity is not more than 100 gm or 300 ml. Determine the weight / ml and calculate the net volume of the contents of each container.

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The average net volume of the contents of the 10 containers is not less than the labeled amount. If labeled amount where the labeled amount is 50 ml or less than NLT 91 % and NMT 109 % If labelled amount is more than 50 ml but not more than 200 ml than NLT 95.5% and NMT 104.5 % If the labelled amount is more than 200 ml but not more than 300 ml than NLT 97% and NMT 103 % IF THE REQUIREMENT IS NOT MEET THAN Additional 10 containers are taken and the average net volume of the contents of the 20 containers is not less than the labeled amount.

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(C) Sterility: When the cream is labeled as sterile, it complies with the tests for sterility. Membrane Filtration: The method needs exceptional skill and special knowledge. It also calls for the routine use of positive and negative controls. A suitable positive control is the occasional use of a known contaminated solution containing a few micro-organisms of different types. Diluting fluids FLUID A : Dissolve 1 g of peptic digest of animal tissue (bacteriological peptone) or its equivalent in water to make 1 liter. filter or centrifuge to clarify, adjust to pH 7.1 ± 0.2, dispense into flasks in 100 ml quantities and sterilize at 121° for 20 minutes.

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Diluting fluids: FLUID A : Dissolve 1 g of peptic digest of animal tissue (bacteriological peptone) or its equivalent in water to make 1 liter. Filter or centrifuge to clarify. Adjust to pH 7.1 ± 0.2, and sterilize at 121° for 20 minutes. FLUID B: If the test sample contains lecithin or oil, use fluid A to each litre of which has been added 1 ml of polysorbate 80. Adjust to pH 7.1 ± 0.2 and sterilize at 121° for 20 minutes.

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Method of test: ( for ointments and creams) Dilute ointments in a fatty base and emulsions of the water-in-oil type to give a fluid concentration of 1% w/v. Sterile diluents such as isopropyl myristate previously rendered sterile by filtration through a 0.22µm membrane filter that has been shown not to have anti-microbial properties under the conditions of test. Filter as rapidly as possible and complete the test as described under for oils and oily solutions beginning wash by the membrane filter.

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REFERENCES: Remington, vol.1 Indian pharmacopoeia Theory and practice of industrial pharmacy Dispensing for pharmaceutical student,by: cooper and guns