Isotretinoin Capsules

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Isotretinoin Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of isotretinoin (C₂₀H₂₈O₂).

[Caution—Isotretinoin is teratogenic. Avoid inhalation and skin contact.]

Avoid exposure to strong light, and use low-actinic glassware in the performance of the following procedures.

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

Procedure

Protect the solutions containing isotretinoin (IRA 1-Mar-2023) from direct light.

Solution A: 0.5% acetic acid in methanol

Solution B: 0.5% acetic acid in water

Mobile phase: Solution A and Solution B (71:29)

Procedure 1 (IRA 1-Mar-2023)

Diluent: Heat 0.1 N sodium hydroxide to about 60°–70°. Cool to room temperature, purge with helium or nitrogen, and store in a plastic container.

System suitability solution: 0.04 mg/mL of USP Isotretinoin RS and 0.02 mg/mL of USP Tretinoin RS in Diluent

Standard solution: 0.04 mg/mL of USP Isotretinoin RS in Diluent

Sample stock solution: Nominally 0.4 mg/mL of isotretinoin in Diluent, prepared as follows. Transfer Capsules (NLT 10) to a suitable volumetric flask. Add Diluent to the volumetric flask to fill about 50% of the volume, sonicate for 1 h with occasional shaking to disperse all of the contents, and dilute with Diluent to volume.

Sample solution: Nominally 0.04 mg/mL of isotretinoin in Diluent from the Sample stock solution. Pass the solution through a suitable membrane Filter of 0.45-μm or finer pore size.

Procedure 2

Procedure 2 may be more suitable for formulations that do not contain surfactant.

Protect solutions containing isotretinoin from light and store at 2°–8°.

Solution C : 0.28 mg/mL of alpha tocopherol in methanol. [Note—Alpha tocopherol is used to prevent the oxidation of isotretinoin in the

Standard solutions.]

Standard stock solution A: About 0.25 mg/mL of USP Isotretinoin RS prepared as follows. Transfer about 25 mg of USP Isotretinoin RS to a 100-mL volumetric flask. Add 1.0 mL of Solution C and about 20 mL of tetrahydrofuran to the same flask. Shake and swirl to dissolve.

Dilute with methanol to volume.

Standard stock solution B: 0.2 mg/mL of USP Tretinoin RS in methanol. Sonicate to dissolve.

System suitability solution: 0.04 mg/mL of USP Isotretinoin RS from Standard stock solution A and 0.02 mg/mL of USP Tretinoin RS from

Standard stock solution B in methanol

Standard solution: 0.005 mg/mL of USP Isotretinoin RS from Standard stock solution A in methanol.

Sample stock solution: Follow the steps given below and the information provided in the Table 1 to prepare the Sample stock solution.

Table 1

1. Pierce one end of each capsule with an awl, cut the capsule and transfer the capsule contents and shells into a 250-mL separating funnel.

2. Rinse the utensils used with the specified volume of methylene chloride into the separating funnel. Swirl and shake vigorously, and transfer the liquid into the volumetric flask with the specified size.

3. Add the same volume of methylene chloride into the separating funnel, swirl and shake vigorously, and transfer the liquid into the same volumetric flask.

4. Rinse the separating funnel several times with the speci fied volume of isopropyl alcohol, transfer each rinsing into the flask, and dilute with isopropyl alcohol to volume.

Sample solution : Nominally 0.005 mg/mL of isotretinoin from the Sample stock solution in methanol. Place the sample flask in a freezer for at least 1 hr to aid the solidi cation of the fat. Upon removing the flask from the freezer, immediately pass the supernatant through a suitable

Filter of 0.2-μm pore size, discarding the first few milliliters of filtrate. (IRA 1-Mar-2023)

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 353 nm. For Identification B, use a diode array detector in the range of 230–400 nm.

Column: 4.6-mm × 25-cm; 10-μm (IRA 1-Mar-2023) packing L1

Autosampler temperature: 5° (for Procedure 2 only) (IRA 1-Mar-2023)

Flow rate: 1.5 mL/min

Injection volume: 20 μL

Run time: NLT 1.5 times the retention time of isotretinoin (IRA 1-Mar-2023)

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for isotretinoin and tretinoin are 1.0 and 1.3, respectively.]

Suitability requirements

Resolution: NLT 2.0 between isotretinoin and tretinoin

(IRA 1-Mar-2023) , System suitability solution

Tailing factor: NMT 2.0 for isotretinoin

(IRA 1-Mar-2023) , System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of isotretinoin () in the portion of Capsules taken:

Result =  (r_U/r_S)  x (C_S/C_U ) × 100

r_U = peak area of isotretinoin (IRA 1-Mar-2023) from the Sample solution

r_S = peak area of isotretinoin (IRA 1-Mar-2023) from the Standard solution

C_S = concentration of USP Isotretinoin RS in the Standard solution (mg/mL)

C_U = nominal concentration of isotretinoin in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Protect the solutions containing isotretinoin from light.

Test 1

Medium

Stage 1: Simulated gastric fluid with pepsin, prepared fresh and purged with nitrogen

Stage 2: 0.13 N sodium hydroxide (5 g/L of sodium hydroxide in water). Prepare fresh, and purge with nitrogen.

Apparatus (see Disintegration 〈701〉): No disks; the apparatus is adjusted so that the bottom of the basket-rack assembly descends to 1.0 ± 0.1 cm from the inside bottom surface of the vessel on the downward stroke; the 10-mesh stainless steel cloth in the basket-rack assembly is replaced with a 40-mesh stainless steel cloth; a 10-mesh stainless-steel cloth is fitted to the top of the basket-rack assembly.

Time: 60 min

Standard solution: Transfer 10 mg of USP Isotretinoin RS to a 200-mL volumetric flask. Add 25.0 mL of Stage 1 Medium and about 150 mL of Stage 2 Medium, sonicate until completely dissolved (about 20 min), and dilute with Stage 2 Medium to volume. Pass 20 mL of this solution through a suitable Filter, discarding the first 5 mL. Dilute 5.0 mL of the filtrate with Stage 2 Medium to 50 mL.

Sample solutions: Perform a dissolution test on each of 6 Capsules. Place 1 Capsule in one of the tubes in each of six basket-rack assemblies. Place each basket in a 1-L beaker containing 100 mL of Stage 1 Medium in a bath having a temperature of 37.0 ± 0.5°. Allow to stand for 30 min. Carefully add 800 mL of Stage 2 Medium to each beaker. With the disintegration apparatus operating, connect each basket-rack assembly to the drive rod in a timed sequence. After 60 min, withdraw 20 mL of Medium (Stage 1 and Stage 2), and immediately pass the solution through a suitable membrane Filter of 0.45-μm pore size. Discard the first 5 mL, and collect the solution in argon-charged glassware. Dilute, if necessary, with Stage 2 Medium to obtain a theoretical concentration of 5.5 μg/mL of isotretinoin, assuming complete dissolution, based on the label claim.

Capsule shell correction solution: Empty the contents of 3 Capsules. Wash the Capsule shells in several 20-mL aliquots of chloroform.

Allow the Capsule shells to air dry. Place the Capsule shells in a 1-L flask containing 100 mL of Stage 1 Medium and 800 mL of Stage 2 Medium. Allow the ask to stand for about 1 h in a bath with a temperature of 37.0 ± 0.5°, stirring occasionally. Filter, and dilute as described for the Sample solutions.

Analysis

Detector: UV 343 nm

Blank: Medium (Stage 1 and Stage 2)

Samples: Standard solution, Sample solutions, and Capsule shell correction solution

Determine the amount of isotretinoin (C₂₀H₂₈O₂ ) dissolved, correcting for the Capsule shell absorbance.

Calculate the percentage of the labeled amount of isotretinoin (C₂₀H₂₈O₂) dissolved:

Result = [(A_U− A_C )/A_S] × (C_S /L) × D × 100

A_U = absorbance of the Sample solutions

A_C = absorbance of the Capsule shell correction solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Isotretinoin RS in the Standard solution (mg/mL)

L = label claim (mg/Capsule)

D = dilution factor for the Sample solutions

Tolerances: NLT 80% (Q) of the labeled amount of isotretinoin (C₂₀H₂₈O₂) is dissolved.

Test 2: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.

Medium: 0.05 M phosphate buffer, pH 7.8, containing 0.5% (w/v) solid N,N-dimethyldodecylamine N-oxide; 900 mL

Apparatus 1: 20-mesh basket; 100 rpm

Time: 90 min

Buffer solution: 3.4 mg/mL of monobasic potassium phosphate. Adjust with phosphoric acid to a pH of 2.10 ± 0.05.

Mobile phase: Methanol and Buffer solution (81:19)

Standard solution: Transfer about 44 mg of USP Isotretinoin RS to a 100-mL volumetric flask. Add 15 mL of 1-propanol, and sonicate for about 15 min. Add 50 mL of Medium, and sonicate for 10 min. Dilute with Medium to volume. Transfer 5.0 mL of the resulting solution to a 100-mL volumetric flask, and dilute with Medium to volume. Dilute this solution with Medium to obtain a final concentration of about (L/1000) mg/mL, where L is the label claim, in mg/Capsule.

Sample solution: Pass a portion of the solution under test through a suitable membrane

Filter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 358 nm

Column: 4.6-mm × 5-cm; 5-μm packing L1

Flow rate: 2.0 mL/min

Injection volume: 10 μL

Run time: NLT 1.5 times the retention time of isotretinoin (IRA 1-Mar-2023)

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of isotretinoin (C₂₀H₂₈O₂) dissolved:

Result = (r_U/r_S)  x (C_S /L) × V × 100

r_U = peak response of isotretinoin (IRA 1-Mar-2023) from the Sample solution

r_S = peak response of isotretinoin (IRA 1-Mar-2023) from the Standard solution

C_S = concentration of USP Isotretinoin RS in (IRA 1-Mar-2023) the Standard solution (mg/mL)

L = label claim (mg/Capsule)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of isotretinoin () is dissolved.

Test 3: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 3.

Medium: Borate buffer, pH 8.0, containing 0.5% cetrimide and 50 mg/L of pancreatin. Dissolve 12.37 g of boric acid and 14.91 g of potassium chloride in water, and dilute with water to 1 L. To 250 mL of this solution, add 19.5 mL of 0.2 M sodium hydroxide solution, and dilute with water to 1 L. Adjust with 0.2 M sodium hydroxide to a pH of 8.00 ± 0.05, if necessary. Add 5 g of cetrimide. Just before starting the test, dissolve a quantity of pancreatin to obtain a final concentration of 50 mg/L; 900 mL.

Apparatus 2: 75 rpm, with sinkers

Time: 90 min

Mobile phase: 0.5% acetic acid in methanol and 0.5% acetic acid in water (71:29)

Standard solution: 0.45 mg/mL of USP Isotretinoin RS in 0.1 N sodium hydroxide. Dilute this solution with Medium to obtain a final concentration of (L/1000) mg/mL, where L is the label claim, in mg/Capsule.

Sample solution: Pass a portion of the solution under test through a suitable membrane

Filter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 353 nm

Column: 4.6-mm × 25-cm; 10-μm packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 μL

Run time: NLT 1.5 times the retention time of isotretinoin (IRA 1-Mar-2023)

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of isotretinoin (C₂₀H₂₈O₂) dissolved:

Result = ( r_U/r_S)  x (C_S /L) × V × 100

r_U = peak response of isotretinoin (IRA 1-Mar-2023) from the Sample solution

r_S = peak response of isotretinoin (IRA 1-Mar-2023) from the Standard solution

C_S = concentration of USP Isotretinoin RS in (IRA 1-Mar-2023) the Standard solution (mg/mL)

L = label claim (mg/Capsule)

V = volume of Medium, 900 mL

Tolerances: NLT 70% (Q) of the labeled amount of isotretinoin (C₂₀H₂₈O₂) is dissolved.

Test 4: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 4.

Medium: 50 mM potassium phosphate, monobasic at pH 7.4 containing 70 mg/L of pancreatin and 4.5% (v/v) lauryl dimethyl amine oxide as a 30% solution, prepared as follows. Dissolve 6.8 g of potassium phosphate, monobasic in 920 mL of water. Adjust by the addition of approximately 35 mL of 1 N sodium hydroxide to a pH of 7.4 ± 0.1. Add 70 mg of pancreatin and 45 mL of 30% solution of lauryl dimethyl amine oxide, and stir gently to mix. The pancreatin should be added on the day of use; 900 mL. [Note—Not all of the pancreatin visibly dissolves.]

Apparatus 2: 75 rpm, with spiral coated sinker1

Time: 90 min

Mobile phase: Methanol, water, and glacial acetic acid (80: 20: 0.5)

Standard stock solution 1: 0.28 mg/mL of USP Isotretinoin RS, prepared as follows. Transfer USP Isotretinoin RS to a suitable volumetric flask, and add methanol equivalent to 10% of the final volume. Sonicate to dissolve, and dilute with Medium to volume.

Standard stock solution 2: 8.8 μg/mL of USP Tretinoin RS, prepared as follows. Transfer USP Tretinoin RS to a suitable volumetric flask, and add methanol equivalent to 20% of the final volume. Sonicate to dissolve, and dilute with Medium to volume to obtain a 0.22-mg/mL solution. Transfer 2 mL of this solution to a 50-mL volumetric flask, and dilute with Medium to volume.

System suitability solution: 45 μg/mL of USP Isotretinoin RS and 0.88 μg/mL of USP Tretinoin RS in Medium from Standard stock solution 1 and Standard stock solution 2

Standard solution: 0.028 mg/mL of USP Isotretinoin RS in Medium, from Standard stock solution 1

Sample solution: Pass a portion of the solution under test through a suitable PVDF membrane

Filter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 353 nm

Column: 4.6-mm × 10-cm; 3-μm packing L1

Temperatures

Autosampler: 4°

Column: 40°

Flow rate: 1.5 mL/min

Injection volume: 10 μL

Run time: NLT 1.5 times the retention time of isotretinoin (IRA 1-Mar-2023)

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for isotretinoin and tretinoin are 1.0 and 1.2, respectively.]

Suitability requirements

Resolution: NLT 3.0 between isotretinoin and tretinoin

(IRA 1-Mar-2023) , System suitability solution

Tailing factor: 0.8–1.3 for isotretinoin

(IRA 1-Mar-2023) , System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of isotretinoin (C₂₀H₂₈O₂) dissolved:

Result = (r_U/r_S)  x (C_S /L) × V × 100

r_U = peak response of isotretinoin (IRA 1-Mar-2023) from the Sample solution

r_S = peak response of isotretinoin (IRA 1-Mar-2023) from the Standard solution

C_S = concentration of USP Isotretinoin RS in the Standard solution (mg/mL)

L = label claim (mg/Capsule)

V = volume of Medium, 900 mL

Tolerances: NLT 75% (Q) of the labeled amount of isotretinoin (C₂₀H₂₈O₂) is dissolved.

Test 5: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 5.

Solution A: 27.2 g/L of potassium phosphate, monobasic in water

Solution B: 8 g/L of sodium hydroxide in water (IRA 1-Mar-2023)

Medium: pH 7.7 phosphate buffer containing 50 mg/L of pancreatin and 1.5% N,N-dimethyldodecylamine-N-oxide, prepared as follows. (IRA 1-Mar-2023) Transfer 250 mL of Solution A and 215 mL of Solution B to a 1000-mL volumetric flask, and dilute with water to volume.

Adjust with Solution B to a pH of 7.7. Add 50 mg of pancreatin and 15 g of N,N-dimethyldodecylamine-N-oxide to this solution (the pancreatin should be added on the day of use); degassed; 900 mL.

Apparatus 2: 75 rpm, with sinkers

Time: 60 min

Mobile phase: Acetonitrile, water, and glacial acetic acid (85: 15: 0.5)

Standard solution: Prepare (IRA 1-Mar-2023) 0.45 mg/mL of USP Isotretinoin RS in methanol. Dilute this solution with Medium to obtain a final concentration of (L/900) mg/mL, where L is the label claim, in mg/Capsule.

Sample solution: Pass a portion of the solution under test through a suitable PVDF membrane

Filter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 353 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 μL

Run time: NLT 1.5 times the retention time of isotretinoin (IRA 1-Mar-2023)

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of isotretinoin (C₂₀H₂₈O₂) dissolved:

Result = (r_U/r_S)  x (C_S/L) × V × 100

r_U = peak response of isotretinoin (IRA 1-Mar-2023) from the Sample solution

r_S = peak response of isotretinoin (IRA 1-Mar-2023) from the Standard solution

C_S = concentration of USP Isotretinoin RS in the Standard solution (mg/mL)

L = label claim (mg/Capsule)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of isotretinoin (C₂₀H₂₈O₂) is dissolved.

Test 6: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 6.

Medium: 1% cetrimide (w/v) in pH 6.8 phosphate buffer containing an amount of pancreatin equivalent to 1750 USP Units of protease activity per liter; degassed; 900 mL

Apparatus 2: 100 rpm

Time: 120 min

Standard stock solutions: Prepare three solutions containing 0.08, 0.2, and 0.32 mg/mL of USP Isotretinoin RS in methanol. Sonicate if necessary.

Standard solutions: Prepare three solutions containing 0.8, 2.0, and 3.2 μg/mL of USP Isotretinoin RS in Medium from the Standard stock solutions. Pass a portion of the solutions through a suitable PVDF membrane Filter of 0.45-μm pore size, and discard the first few milliliters of the filtrate.

Sample stock solution: Pass a portion of the solution under test through a suitable polyethylene full flow Filter of 35-μm pore size, and then through a suitable PVDF membrane Filter of 0.45-μm pore size. Discard the first few milliliters of the filtrate.

Sample solution: Transfer the Sample stock solution to a suitable volumetric flask and dilute with Medium to volume according to Table 2.

Table 2 (IRA 1-Mar-2023)

Instrumental conditions

Mode: UV

Analytical wavelength:

(IRA 1-Mar-2023) 348 nm

Blank: Medium

Analysis

Samples: Standard solutions and Sample solution

Calibration curve: Construct a calibration curve of the concentration of USP Isotretinoin RS (μg/mL) versus absorbance from the Standard

solutions. The linear regression coe

cient is NLT 0.99.

Determine the concentration of isotretinoin in the Sample solution from the Calibration curve, and calculate the percentage of the labeled amount of isotretinoin (C H O ) dissolved:

Result = C_U× V × (D/L) × (1/F) × 100

C_U = (IRA 1-Mar-2023) concentration of isotretinoin in the Sample solution determined from the Calibration curve (IRA 1-Mar- 2023) (μg/mL)

V = volume of Medium, 900 mL

D = dilution factor for the Sample solution (see Table 2 (IRA 1-Mar-2023) )

L = label claim (mg/Capsule)

F = conversion factor, 1000 μg/mg

Tolerances: NLT 80% (Q) of the labeled amount of isotretinoin (C₂₀H₂₈O₂) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Change to read:

Organic Impurities

Mobile phase: Hexanes, ethyl acetate, and glacial acetic acid (970: 30: 0.1)

Diluent: (IRA 1-Mar-2023) Transfer 50 g of sodium bicarbonate to 1000 mL of methylene chloride, shake, and allow to stand overnight. At the time of use, Filter suitable portions of this solution, and add 10 mg of butylated hydroxytoluene per milliliter of solution.

System suitability stock solution: 1 mg/mL each of USP Isotretinoin RS and USP Tretinoin RS in Diluent (IRA 1-Mar-2023)

System suitability solution: 0.01 mg/mL each of USP Isotretinoin RS and USP Tretinoin RS in hexanes, from the System suitability stock solution

Standard stock solution: 0.5 mg/mL of USP Tretinoin RS in Diluent (IRA 1-Mar-2023)

Standard solution: 1.0 μg/mL of USP Tretinoin RS in hexanes, from the Standard stock solution

Sample stock solution: Take a number of Capsules equivalent to about 200 mg of isotretinoin, and with a sharp blade carefully open the

Capsules without loss of material. Transfer the contents by pipetting 5 mL of Diluent (IRA 1-Mar-2023) over each Capsule, and rinsing with hexanes. Collect the washings in a 500-mL volumetric flask, dilute with hexanes to volume, and mix.

Sample solution: Nominally 0.1 mg/mL of isotretinoin from Sample stock solution (IRA 1-Mar-2023) in hexanes.

(IRA 1-Mar-2023)

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 365 nm

Column: 4.6-mm × 25-cm; packing L3

Flow rate: 1 mL/min

Injection volume

System suitability: 20 μL

Analysis: 50 μL

Run time: NLT 2 times the retention time of isotretinoin

System suitability

Sample: System suitability solution

[Note—The relative retention times for isotretinoin and tretinoin are about 0.75 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between isotretinoin and tretinoin

Tailing factor: NMT 2.5 for isotretinoin (IRA 1-Mar-2023)

Relative standard deviation: NMT 2.0% for tretinoin (IRA 1-Mar-2023)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Capsules taken:

Result = (r_U/r_S)  x (C_S/C_U) × 100

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of tretinoin from the Standard solution

C_S = concentration of USP Tretinoin RS in the Standard solution (mg/mL)

C_U = nominal concentration of isotretinoin in the Sample solution (mg/mL)

Acceptance criteria

Any individual impurity: NMT 1.0%

Total impurities: NMT 1.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, protected from light. Store at controlled room temperature in a dry place.

Change to read:

Labeling: The label states with which Procedure in the Assay the product complies only if Procedure 1 is not used. (IRA 1-Mar-2023) When

more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Isotretinoin RS

USP Tretinoin RS

1 A suitable sinker is available as catalog #CAPWHT-02 from www.qla-llc.com.