Doxycycline Hyclate Delayed-Release Tablets
DEFINITION
Doxycycline Hyclate Delayed-Release Tablets contain an amount of Doxycycline Hyclate equivalent to NLT 90.0% and NMT 120.0% of the labeled amount of doxycycline (C22H24N2O8).
IDENTIFICATION
• The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
[NoteThroughout the following procedure, protect the Standard solution and Sample solution from light. ]
Mobile phase:
Transfer 0.77 g of ammonium acetate, 0.75 g of sodium hydroxide, 0.50 g of tetrabutylammonium hydrogen sulfate, and 0.40 g of edetate disodium to a 1000-mL volumetric flask. Add 850 mL of water, and dissolve. Add 70 g of tertiary butyl alcohol with the aid of water, dilute with water to volume, and adjust with acetic acid or ammonium hydroxide to a pH of 9.00 ± 0.05.
Standard solution:
1.16 mg/mL of doxycycline hyclate in methanol and water (1:9). [NoteTransfer USP Doxycycline Hyclate RS to a suitable volumetric flask, and add methanol to 10% of the final volume. Sonicate for 5 min or until dissolved. Dilute with water to volume. ]
Sample solution:
Equivalent to 1 mg/mL of doxycycline in a mixture of methanol and water (1:9) from NLT 10 Tablets, crushed. [NoteWeigh and crush NMT 2 Tablets at a time in a suitable mortar. Transfer a weighed portion of the powder to a suitable volumetric flask, add methanol to 10% of the final volume, and sonicate. Dilute with water to volume, sonicating as necessary. Pass through a suitable filter. ]
Chromatographic system
Mode:
LC
Detector:
UV 270 nm
Column:
4.6-mm × 25-cm; packing L21
Column temperature:
52 ± 2
Flow rate:
1 mL/min
Injection size:
15 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0% from six replicate injections
Analysis
[NoteThe run time is 1.7 times the retention time of the doxycycline peak. ]
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of C22H24N2O8 in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
90.0%120.0%
PERFORMANCE TESTS
• Dissolution, Method B 711
Acid stage
Medium:
0.06 N hydrochloric acid; 900 mL, degassed with helium
Apparatus 1:
50 rpm
Time:
20 min
Standard solution:
0.128 mg/mL of USP Doxycycline Hyclate RS in Medium. Calculate the concentration, CS, in mg/mL of doxycycline, using the designated potency, in µg of doxycycline/mg of USP Doxycycline Hyclate RS. [NoteSonicate if necessary to dissolve. ]
Sample solution:
Pass portions of the solution under test through a suitable PVDF filter of 0.45-µm pore size.
Detector:
UV 346 nm
Cell:
0.1-cm quartz
Blank:
Medium
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of doxycycline (C22H24N2O8) dissolved:
Result = (AU/AS) × (CS/L) × V × 100
Tolerances
Level 1 (6 Tablets tested):
No individual value is more than 30% of the labeled amount of doxycycline (C22H24N2O8) dissolved in 20 min.
Level 2 (6 Tablets tested):
NMT 2 individual values of the 12 tested are greater than 30% of the labeled amount of doxycycline (C22H24N2O8) in 20 min.
Buffer stage
[NoteConduct this stage of testing on separate Tablets, selecting those that were not previously subjected to the Acid stage testing. ]
Medium:
pH 5.5 neutralized phthalate buffer (see Reagents, Indicators, and SolutionsBuffer Solutions); 900 mL, degassed
Apparatus 1:
50 rpm
Time:
30 min
Standard solution:
0.128 mg/mL of USP Doxycycline Hyclate RS in Medium. Calculate the concentration, CS, in mg/mL of doxycycline, using the designated potency, in µg of doxycycline/mg of USP Doxycycline Hyclate RS. [NoteSonicate if necessary to dissolve. ]
Sample solution:
Pass portions of the solution under test through a suitable PVDF filter of 0.45-µm pore size.
Analysis:
Determine the percentage of doxycycline (C22H24N2O8) dissolved by the procedure described for the Acid stage.
Tolerances:
NLT 85% (Q) of the labeled amount of doxycycline (C22H24N2O8) is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
IMPURITIES
Organic Impurities
[NoteThroughout the following procedure, protect solutions containing doxycycline from light. ]
• Procedure
Mobile phase, Sample solution, and Chromatographic system:
Proceed as directed in the Assay.
Standard stock solution:
1.16 mg/mL of doxycycline hyclate in methanol and water (1:9). [NoteTransfer USP Doxycycline Hyclate RS to a suitable volumetric flask, and add methanol to 10% of the final volume. Sonicate for 5 min or until dissolved. Dilute with water to volume. ]
Standard solution:
0.02 mg/mL of doxycycline from Standard stock solution
Sensitivity solution:
1 µg/mL of doxycycline from the Standard solution
System suitability stock solution:
0.04 mg/mL each of USP Oxytetracycline Hydrochloride RS, USP Methacycline Hydrochloride RS, and USP Doxycycline Related Compound A RS
System suitability solution:
Transfer 5 mL of the Standard stock solution into a 25-mL volumetric flask. Heat on a steam bath for 60 min, and gently evaporate to dryness on a hot plate (partial degradation of doxycycline to 4-epidoxycycline). Add 3 mL of the System suitability stock solution to the flask, and dilute with water to volume. Pass through a suitable filter.
System suitability
Samples:
Standard solution, Sensitivity solution, and System suitability solution
Suitability requirements
Signal-to-noise ratio:
NLT 10 for doxycycline, Sensitivity solution
Resolution:
NLT 1.5 between doxycycline and 6-epidoxycycline, System suitability solution
Tailing factor:
NMT 2.0, Standard solution
Relative standard deviation:
NMT 5.0%, Standard solution
Analysis
[NoteThe run time is 1.7 times the retention time of the doxycycline peak. ]
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Impurity Table 1
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers. Store at controlled room temperature.
• USP Reference Standards 11
USP Doxycycline Related Compound A RS
6-Epidoxycycline, or (4S,4aR,5S,5aR,6S,12aS)-4-(dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide. C22H24N2O8 444.43
USP Oxytetracycline Hydrochloride RS
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 2988
Pharmacopeial Forum: Volume No. 36(4) Page 912
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