Pharmacopoeial quality control PDF

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Pharmacopoeial quality control tests for tablets •      

Pharmacopoeial quality control tests for tablets Uniformity of weight (mass) (BP Appendix XII G, Ph. Eur. 2.9.5) Uniformity of content (BP Appendix XII H, Ph. Eur. 2.9.6) Disintegration test (BP Appendix XII A, Ph. Eur. 2.9.1) Dissolution test (BP Appendix XII D, Ph. Eur. 2.9.3) Resistance to Crushing of Tablets (BP Appendix XVII H, Ph. Eur. 2.9.8) Friability (BP Appendix XVII G, Ph. Eur. 2.9.7)

• Uniformity of weight and content  Does the dosage form contain the correct amount of drug?  Is the drug content reproducible between tablets?  Is the manufacture of the dosage from reproducible?

IS THE PATIENT GOING TO RECEIVE THE CORRECT AMOUNT OF DRUG FROM EACH DOSE? • Uniformity of weight (mass) Procedure: 

Weigh 20 tablets selected at random and determine the average and individual weight.

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PASS if no more than two of the individual weights deviate from the average weight by more than the percentage deviation shown in the table and none may deviate by more than twice that percentage.

• Uniformity of content (flow diagram) • Determining drug content  Prepare tablets for analysis  Grind, dissolve and filter  Make up to known volume  Assay by comparing against suitable standards  UV absorbance  λmax of drug  Calibration curve with known standards • Determining drug content  Prepare tablets for analysis  Grind, dissolve and filter  Make up to known volume  Assay by comparing against suitable standards  UV absorbance  λmax of drug  Calibration curve with known standards • Disintegration and dissolution

• Disintegration and dissolution testing  Will the tablet disperse and dissolve in the correct environment?  Will the tablet disperse and dissolve in the optimum time? WILL THE PATIENT BE ABLE TO ABSORB A THERAPEUTIC DOSE OF THE DRUG? • Disintegration Procedure: 

6 tablets taken at random are placed individually in a tube. Repeat three times, so, a total of 18 tablets.

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The tubes are vertically raised and lowered 50-60 mm, 28-32 times a minute, in a “water” bath.

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PASS if all 18 tablets have completely disintegrated within the specified time (see table on next slide). FAIL if any tablet has not disintegrated.

• Disintegration testing parameters • Dissolution testing Procedure: •

Individually place 3 - 6 tablets into a dissolution vessel containing 900 ml medium (36.5°C37.5 °C). Set paddles or basket rotating at a defined rpm.

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Withdraw samples at 45 min, prescribed intervals or continuously. Samples should be taken from a point halfway between the surface and the top of the paddle, not less than 10 mm from the vessel wall.

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Replace volume with an equal amount of medium.

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Determine the amount of active ingredient in the sample. Pass if >70% has dissolved by 45 min. If one fails, a further 6 tablets may be tested. To pass, all must comply • Dissolution data interpretation  Shape of the dissolution graph can tell you a lot about the nature of drug bioavailability and the controlling factors of this process • Determining drug content for dissolution assays  Similar methodology to drug content analysis  Assay development using UV spectroscopy  Samples already in solution  λmax of active  Calibration curve with known standards

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Crushing and Friability Testing

 How robust are the tablets?  Is the quality of the tablets reproducible?  Will the tablets withstand handling, processing and transport?

WILL THE PATIENT RECEIVE A GOOD QUALITY DOSAGE FORM DELIVERING 100% OF THE INTENDED DOSE?

• Crushing strength measurements Procedure: 

Select 10 tablets at random and place in a reproducible manner between the jaws of the instrument. Denote orientation of tablet with regard to shape, break marks or inscriptions.

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Apply pressure and measure the force at the break.

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Expression of results: Mean force is expressed in Newtons (N). Also provide the maximum and minimum force measured, as well as information regarding the instrument and tablet orientation.

Calculate the tensile strength of each tablet and the mean ± standard deviation. • Resistance to crushing of tablets Crushing strength = Hardness = The minimum diametric compression force required to fracture a tablet  Tablet diameter and thickness affect the force necessary to break it. Tensile strength  

Where  is the tensile strength (N/m2), P the crushing strength (N), D the diameter (m) and H the tablet thickness (m) Tensile strength is expressed in N/m2 or Pa, MPa.

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Crushing strength measurements Kilogram (kg) – The kilogram is recognised by the SI system as the primary unit of mass.

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Newton (N) – The Newton is the SI unit of force and is the unit that should be used for tablet hardness testing. 9.807 Newtons = 1 kilogram.

Pound (lb) – Technically a unit of mass but can also be used for force and should be written as pound force or lbf in this case. Sometimes used for tablet strength testing in North America, but it is not an SI unit. 1 kilogram = 2.204 pounds • Friability: Resistance to abrasion • Friability measurements Procedure: •

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If a single tablet weighs < 0.65 g, select 20 tablets at random. If a single tablet weighs > 0.65 g, select 10 tablets at random.

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Tablets are de-dusted, weighed [W0], placed in a Perspex drum (Copley Friabilator) and tumbled (rotated 100 times [4min]).

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After de-dusting they are reweighed [W].

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PASS if...