Scopeia

• Monitor periodically the critical test parameters of the dissolution test equipment during use including volume and temperature of the dissolution medium and rotation Speed.

 

• Testing procedures for Conventional-release (or immediate-release) solid dosage forms:

  • Place the stated volume of the dissolution medium (± 1 per cent) in the vessel of the specified apparatus.
  • Assemble the apparatus, equilibrate the dissolution medium to 37 ± 0.5 °C, and remove the thermometer.
  • The test may also be carried out with the thermometer in place, provided it shows that results equivalent to those obtained without the thermometer are obtained.
  • Place 1 dosage unit in the apparatus, taking care to exclude air bubbles from the surface of the dosage unit.
  • Operate the apparatus at the specified rate. Within the time interval specified, or at each of the times stated, withdraw a specimen from a zone midway between the surface of the dissolution medium and the top of the rotating basket or blade, not less than 1 cm from the vessel wall.
  • Where multiple sampling times are specified, replace the aliquots withdrawn for analysis with equal volumes of fresh dissolution medium 37 °C or, where it can be shown that replacement of the medium is not necessary, correct for the volume change the calculation.
  • Keep the vessel covered for the duration the test and verify the temperature of the medium at suitable times. Perform the analysis using a suitable assay method. Repeat the test with additional dosage units if needed.
  • If automated equipment is used for sampling or the apparatus is otherwise modified, verification that the modified apparatus will produce results equivalent to those obtained with the apparatus described in this chapter, is necessary.
  • Dissolution medium: A suitable dissolution medium shall be used. The volume specified refers to measurements made between 20 °C and 25 °C. If the dissolution medium is a buffered solution, adjust the solution so that its pH is within 0.05 units of the specified pH.
  • Dissolved gases can cause bubbles to form, which may change the results of the test. In such cases, dissolved gases must be removed prior to testing Time. Where a single time specification is given, the test may be concluded in a shorter period if the requirement for minimum amount dissolved is met. Samples are to be withdrawn only at the stated times, within a tolerance of ± 2 per cent.

 

• Testing procedures for Prolonged-release solid dosage forms:

  • Proceed as described for conventional-release dosage forms.
  • Dissolution medium. Proceed as described for conventional-release dosage forms.
  • The test-time points, generally 3, are expressed in hours.
  • Testing procedures for Delayed-release solid dosage forms:
• Use Method A or Method B as mentioned in the individual product monograph.

 

•   Method A:
  • Acid stage. Place 750 ml of 0.1 M hydrochloric acid in the vessel, and assemble the apparatus.
  • Allow the medium to equilibrate to a temperature of 37 ± 0.5 °C.
  • Place 1 dosage unit in the apparatus, cover the vessel and operate the apparatus at the specified rate.
  • After of operation in 0.1 M hydrochloric acid, withdraw an aliquot of the fluid and proceed immediately as directed under Buffer stage.
  • Perform an analysis of the aliquot using a suitable assay method.
  • Buffer stage. Complete the operations of adding the buffer and adjusting the pH within 0.05 mm.
  • With the apparatus operating at the rate specified, add to the in the vessel 250 ml of 0.20 M solution of trisodium phosphate dodecahydrate R that has been equilibrated 37 ± 0.5 °C.
  • Adjust, if necessary, with 2M hydrochloric acid or 2M sodium hydroxide to a pH of 6.8 ± 0.05.
  • Continue to operate the apparatus for 45 mm, or for specified time. At the end of the time period, withdraw an aliquot of the fluid and perform the analysis using suitable assay method.

 

• Method B:
  • Acid Stage. Place 1000 ml of 0.1 M hydrochloric acid in the vessel and assemble the apparatus.
  • Allow the medium to equilibrate to a temperature of 37 ± 0.5 °C.
  • Place 1 dosage unit in the apparatus, cover the vessel, and operate the apparatus at the specified rate.
  • After of operation in 0.1 M hydrochloric acid, withdraw an aliquot of the fluid, and proceed immediately as directed under Buffer stage.
  • Perform an analysis of the aliquot using a suitable assay method.
  • Buffer stage. For this stage of the procedure use buffer that has previously been equilibrated to a temperature of 37 ± 0.5 °C.
  • Drain the acid from the vessel and add 1000 ml of pH 6.8 phosphate buffer, prepared by mixing 3 volumes of 0.1 M hydrochloric acid with 1 volume 0.20 M solution of trisodium phosphate dodecahydrate and adjusting, if necessary, with 2 M hydrochloric acid or 2 M sodium hydroxide to a pH of 6.8 ± 0.05.
  • This Also be accomplished by removing from the apparatus the vessel containing the acid and replacing it with another vessel, containing the buffer and transferring Dosage unit to the vessel containing the buffer.
  • Continue to operate the apparatus for 45 mm, or for the specified time. At the end of the time period, withdraw an aliquot of the fluid and perform the analysis using a suitable assay method. Time.
  • All test times stated are to be observed within a tolerance of ± 2 per cent, unless otherwise specified.

 

• Interpretation
  • Conventional-release solid dosage forms criteria:
    • Unless otherwise specified, the requirements are met if the quantities of active substance dissolved from the dosage units tested conform to Table-1.
    • Continue testing through the 3 levels unless the results conform at either S1 or S2.
    • The quantity Q, is the specified amount of dissolved active substance, expressed as a percentage of the labeled content; the 5 percent, 15 percent, and 25 percent values in the Table are percentages of the labeled content so that these values and Q are in the same terms.

Table-1

 

Level	Number tested	Acceptance criteria
S1	6	Each unit is not less than Q + 5 percent
S2	6	Average of 12 units (S1 + S2) is equal to or greater than Q. and no unit is less than Q – 15 percent
S3	12	Average of 24 units (S1 + S2 + S3) is equal to or greater than Q. Not more than 2 units are less than Q – 15 percent and no is less than Q – 25 percent.

• Prolonged-release dosage forms criteria
  • Unless otherwise specified, the requirements are met the quantities of active substance dissolved from the dosage units tested conform to Table-2.
  • Continue testing through the 3 levels unless the results conform at either L1 or L2 Limits on the amounts of active substance dissolved are expressed in terms of the percentage of labeled
  • The limits embrace each value of Q the amount dissolved at each specified fractional dosing interval. Where more than one range is specified, the acceptance criteria apply individually to each range.

Table-2

Level	Number tested	Acceptance criteria
L1	6	No individual value lies outside each of the stated ranges and no individual value is less than the stated amount at the final test time.
L2	6	The average value of the 12 units (L1 + L2) lies within each of the stated ranges and is not less than the stated amount at the final test time; None is more than 10 percent of labeled content outside each of the stated ranges; and none is more than 10 of labeled below the stated amount at the final test time.
L3	12	The average value of the 24 units (L1 + L2 + L3) lies within each of the stated ranges, and is not less than the stated amount at the final test time; Not more than 2 of the 24 units are more than 10 percent of labeled content outside each of the stated ranges; Not more than 2 of the 24 units are more than 10 percent of labeled content below the stated amount of the final test time; and none of the units is more than 20 percent of labeled content outside each of the stated ranges or more than 20 percent of labeled content below the stated amount at the final test time.

• Delayed-release dosage forms criteria
  • Acid stage. Unless otherwise specified, the requirements of this portion of the test are met if the quantities, based on percentage of the labeled content of active substance dissolved from the units tested conform to Table-3.
  • Continue testing through the 3 levels unless the results of both acid and buffer stages conform at an earlier level.

Table-3

Level	Number tested	Acceptance criteria
A1	6	No individual value exceeds 10 percent dissolved
A2	6	The average of value of the 12 units (A1 + A2) is not more than 10 percent dissolved, and no individual unit is greater than 25 percent dissolved.
A3	12	The average value of the 24 units (A1 + A2 + A3) is not more than 10 percent dissolved, and no individual unit is greater than 25 percent dissolved.

• Buffer stage. Unless otherwise specified, the requirements met if the quantities of active substance dissolved from units tested conform to Table -4.
• Continue testing through the 3 levels unless the results of both stages conform to an earlier level.
• The value of Q in Table-4 is 75 percent dissolved unless otherwise specified. The quantity, Q, is specified total amount of active substance dissolved in both the acid and buffer stages, expressed as a percentage of the labeled content.
• The S per cent, 15 percent and 25 percent values in the Table are percentages of the labeled content so that these values and Q are in the same terms.

 

Table-4

Level	Number tested	Acceptance criteria
B1	6	No unit is less than Q + 5 percent
B2	6	The average of value of the 12 units (B1 + B2) is equal to or greater than Q, and no unit is less than Q – 15 percent
B3	12	The average value of the 24 units (B1 + B2 + B3) is equal to or greater than Q, not more than 2 units are less than Q – 15 percent, and no unit is less than        Q – 25 percent