Dexamethasone
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The document discusses dexamethasone, a synthetic corticosteroid, detailing its properties, manufacturing processes, testing methods, and regulatory compliance for tablet and ophthalmic suspension forms. It describes procedures for content uniformity, dissolution testing, and chromatographic assays to ensure that products contain the appropriate amount of dexamethasone and meet quality standards. It also lists specifications for packaging, storage, and testing results confirming that products comply with the required ranges for efficacy and safety.
Dexamethasone
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- 4. Dexamethasone is a synthetic (man-made) corticosteroid. Corticosteroids are naturally- occurring chemicals produced by the adrenal glands located above the kidneys. Corticosteroids affect the function of many cells within the body and suppress the immune system. Corticosteroids also block inflammation and are used in a wide variety of inflammatory diseases affecting many organs. The FDA approved dexamethasone in October 1958. DEXAMETHASONE
- 5. Dexamethasone Tablets Contain Dexamethasone. CONTENT OF DEXAMETHASONE: 95.0 to 105.0% of the stated amount. ACTION AND USE: Glucocorticoid. DEXAMETHASONE TABLETS
- 6. Powdered Tablets containing 20 mg of dexamethasone + 5ml of 0.1M NaOH. Add 50ml dichlorometh ane mix with aid of ultrasound (20min) Filter layer of dichlorometh ane , evaporate it with using a rotary evaporator Dry residue at 105℃ for 2 hours. Check the absorption at infrared spectrum of the dried residue. IDENTIFICATION
- 7. Tablets containing less than 2mg or less than 2% w/w of dexamethasone comply with the requirement Carry out the method for liquid chromatography UNIFORMITY OF CONTENT Tablet +sufficient methanol (50%) solution of 0.0025% w/v of dexamethasone shake (10min) filter
- 8. (2) CHROMATOGRAPHICCONDITIONS: Stainless steel column Isocratic elution Flow rate of 1.4ml/min Ambient column temperature Detection wavelength of 238nm Inject 20µL of each solution 0.0025% w/v of dexamethasone in methanol (50%)
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- 10. Tablets containing less than 2mg or less than 2% w/w of dexamethasone ASSAY Use the average of the 10 individual results obtained in the test for uniformity of content
- 11. Tablets containing 2mg or more than 2% w/w of Dexamethasone: (1) ASSAY Powdered tablets + 2.5 mg dexamethasone + 20ml methanol shake (20min) filter
- 12. (2) STORAGE: Dexamethasone tablets should be protected from light 0.0125% w/v of dexamethasone BPCRS in methanol 50%
- 13. USP
- 14. Dexamethasone tablet contains not less than 90.0 %and not more than 110.0% of the label amount of dexamethasone. Packaging And Storage: preserve in well close container. Introduction
- 15. Process by which solvent enter solid substance to yield a solution. Dissolution medium: solvent or medium in which substance is dissolve. Medium: dilute hydrochloric acid (1 in100ml). Apparatus 1:100 RPM. Time:45min. Standard solution: prepare as directed for std. preparation and assay of steroids, using dexamethasone RS. Dissolution
- 16. Extract a filtered aliquot (dissolution medium) about200 micro gm. of dexamethasone with 3 portions of chloroform(15ml).Evaporate this extract to dryness on steam bath, cool it and dissolve the residue(extract) in 20ml of alcohol. Calculate the portion in mg of dexamethasone dissolve. Tolerance: not less than 70% label amount of dexamethasone is dissolve in 45 minutes. Procedure
- 17. DIFFERENCE B/W CONTENT UNIFORMITY & ASSAY Uniformity of content is by two methods by weight variation and by content uniformity. Weight variation means performing assay and relating with individual unit of dosage form. Content uniformity means for ten sample (dosage unit) individually analysed.
- 18. PROCEDURE FOR CONTENT UNIFORMITY STANDARD SOLUTION: Prepare as directed for Standard Preparation under Assay for steroids using USP Dexamethasone RS. TEST SOLUTION: Place 1 tablet in a separator with 15ml of water and swirl to disintegrate completely. Extract with four 10ml portion through chloroform-washed cotton into 50ml volumetric flask. Add chloroform to volume and mix. Pipette a volume of this solution equivalent to 200microgram of dexomethasone into a glass stoppered 50ml conical flask.
- 19. Proceed as directed for Procedure under Assay for steroids, except to allow to stand in the dark for 45 mins. Calculate the quantity in mg of total steroids as C22H29FO5 in the tablet by the formula: (C/V)(AU / AS) In which V is the volume in ml of the aliquot taken to prepare the Test solution.
- 20. ASSAY MOBILE SOLVENT: Prepare a suitable aqueous solution of acetonitrile approximately 1 in 3 , such that the retention time of dexomethasone is b/w 3 mins and 6 mins. STANDARD PREPARATION: Dissolve an accurately weighd quantity of USP Dexamethasone RS in dilute methanol to obtain a solution having a known concentration of about 0.1 mg per ml.
- 21. ASSAY PREPARATION: Weigh and finely powder not fewer than 10 tablets. Weigh accurately a portion of powder equivalent to about 5 mg of dexamethasone. Transfer to a 50ml volumetric flask and add 30 ml of dilute methanol. Sonicate the flask for about 2 mins , shake by mechanical means for 30 mins. Dilute with the same solvent to volume. Filter a portion of mixture through a suitable filter to obtain a clear filtrate.
- 22. PROCEDURE Introduce equal volumes of the Assay preparation and the Standard preparation into a high pressure liquid chromatograph operated at room temperature by means of a loop injector, adjusting the specimen size other operating parameters such that the peak obtained with the Standard preparation is about 0.6 full scale. The apparatus is fitted with a 4.6 mm × 30 cm column packed with packing L1 and is equipped with an UV detector capable of monitoring absorption at 254 nm and a suitable recorder. In a suitable chromatogram , the coefficient of variation for five replicate injections of a single specimen is not more than 3 %.
- 23. Measure the responses of the peaks at identical retention times obtained with the Assay preparation and the Standard preparation. Calculate the quantity in mg of C22H29FO5 in the portion of tablets taken by the formula: 50C(ru/rs) In which C= is the concentration in mg per ml of USP Dexamethasone RS in the Standard preparation . ru and rs = are the peak responses obtained from the Assay preparation and the Standard preparation.
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- 25. Dexamethasone suspension: a sterile suspension of dexamethasone in a suitable vehicle. CONTENT OF DEXAMETHASONE: 95.0 to 105.0% of the stated amount. ACTION AND USE: Glucocorticoid. Introduction:
- 26. Eye drop containing 20 mg of dexamethasone + 5ml of 0.1M NaOH. Add 50ml dichloromethane mix with aid of ultrasound (20min) Filter layer of dichloromethane , evaporate it with using a rotary evaporator Dry residue at 105℃ for 2 hours. Check the absorption at infrared spectrum of the dried residue. IDENTIFICATION
- 27. PARTICLE SIZE Examine using an automated light obscuration instrument Not more than 20 particle >25µm Not more than 2 particle >50µm No particles >90µm. ACIDITY pH,5.0 to 6.0 TESTS:
- 28. •Carry out the method for Liquid chromatography •Dispense a quantity of eye drop containing 20mg of dexamethasone in 70ml of mobile phase, mix the aid of ultrasound for 10 min, dilute with sufficient water to produce 100 ml and filter. •0.02% w/v of dexamethasone BPCRS •0.01% w/v of dexamethasone impurity standard BPCRS. ASSAY
- 29. Related susbstance may be used : SYSTEM STABILITY: Test in not valid unless chromatogram obtained with solution (3). Resolution factor between the peaks id due to impurity 3 and dexamethasone is atleast 1.5 the chromatogram supplied with dexamethasone impurity standard BPGRS. CHROMATOGRAPHIC CONDITIONS:
- 30. •Calculate the content of C22H29FO5 in the eyedrop using the declared content of C22H29FO5 in dexamethasone BPGRS. DETERMINATION OF CONTENT •Should be stored in accordance with manufacturer’s instructions. STORAGE
- 32. USP
- 33. 131027
- 34. Dexamethasone ophthalmic suspension of dexamethasone containing a suitable antimicrobial preservative It may contain suitable buffers, stabilizers and suspending and viscosity agent It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of 22H29FO5 INTRODUCTION
- 35. Preserve in tight containers PACKAGING AND STORAGE
- 36. Transfer a volume of ophthalmic suspension equivalent to about 2.5 mg of dexamethasone to a test tube ,add ml of chloroform and shake. Centrifuge and apply 10µL of the chloroform layer and 10µL of a standard solution of usp .Dexamethasone RS in chloroform containing 500µg per ml on a thin layer chromatographic plate coated with a 0.25mm layer of chromatographic silica gel mixture Develop the chromatogram in solvent A as directed under single steroid assay IDENTIFICATION:
- 37. Mark the solvent front and locate the spots on the plate by spraying with a 1 in 5 solution of p-toluene sulfonic acid in a mixture of 9 volume of alcohol and volume of propylene glycol and heating until spots appear The Rf value of the principal spot obtained from the solution under test corresponds to that obtained from the standard solution
- 38. STERILITY Should be meet the requirement Media Membrane Filtration Aqueous Solutions Direct Inoculation of the Culture Media Observation And Interpretation Of Results Rabbit Pyrogen Test Pyrogen Test Spark Test Leaker Test
- 39. The pH should be between 5.0 and 6.0
- 40. ASSAY MOBILE PHASE water acetonitrile (60:40) STANDARD PREPARATION USP Dexamethasone RS mobile phase dilute if necessary concentration of 0.12 mg/mL
- 41. ASSAY ASSAY PREPARATION measured volume of Opthalmic Suspension (3mg of dexamethasone) 25 mL volumetric flask dilute with mobile phase to volume & mix CHROMATOGRAPHIC SYSTEM 254-nm detector 4.6-mm*25-cm column (packing L1) Flow rate is about 2 mL/min Chromatograph standard preparation & record peak response column efficiency is not < 1750 , tailing factor is not > 3.0 & the relative SD for replicate injection is not > 3.0%
- 42. Separately inject equal volumes of the standard preparation and the assay preparation into the chromatograph, record the chromatographs and measure the responses for the major peaks.Calculate the quantity in mg of Dexamethasone in each mL of the opthalmic suspension using formula: 25(C/V)(ru/rs)
- 44. TEST RANGE/ LIMIT RESULT COMMENTS/ REMARKS Identification IR spectrum Concordant with RS 089 Concordant. Identified. Uniformity of content L1 (maximum allowed acceptance value) is 15 A.V= 5.6 Accepted. Assay 95-105% 97% Accepted. Dexamethasone tablets BP
- 45. TEST RANGE/ LIMIT RESULT COMMENTS/ REMARKS Identification RF value corresponds to standard. Corresponded. Identified. Dissolution Not less than 70% of labeled amount of C22H29FO5 is dissolved in 45minutes. 85% C22H29FO5 is dissolved. Passed. Uniformity of dosage units L1 (maximum allowed acceptance value) is 15 A.V = 5.6 Accepted. Assay 90-110 % 97% Accepted. Dexamethasone tablets USP
- 46. DEXAMETHSONE OPTHALMIC SUSPENSION BP TEST RANGE/ LIMIT RESULT COMMENTS/ REMARKS Identification IR spectrum Concordant with RS 089 Concordant. Identified. Particle size Not more than 20 particles >25µm Not more than 2particles >50µm No particle >90µm 19paricles are >25µm 1 particle is >50µm No particle is >90µm Accepted. Acidity pH 5.0-6.0 pH is 5.6 Accepted. Assay 95-105% 97% Accepted.
- 47. DEXAMETHSONE OPTHALMIC SUSPENSION USP TEST RANGE/ LIMIT RESULT COMMENTS/ REMARKS Identification RF value corresponds to standard. Corresponded. Identified. Sterility Should be no evidence of microbial growth. The product complies with the test for sterility. Passed the sterility test. pH 5.0-6.0 pH is 5.6 Accepted. Assay 90-110 % 97% Accepted.
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