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VIN NN DICLOFENAC Tabellae Diclofenaci natrii L vin nn bao tan trong rut cha diclofenac natri.

Ch phm phi p ng cc yu cu trong chuyn lun "Thuc vin nn" mc "Vin bao" (Ph lc 1.20) v cc yu cu sau: Hm lng diclofenac natri, C14H10Cl2NNaO2, t 90,0% n 110,0% so vi hm lng ghi trn nhn. Tnh cht Vin bao mu ng nht, kh. nh tnh Loi b lp bao ca vin, nghin thnh bt mn. Ly mt lng bt tng ng vi khong 150 mg diclofenac natri. Thm 0,5 ml acid acetic (TT) v 15 ml methanol (TT), lc siu m. Lc dung dch qua giy lc vo cc ng 15 ml nc, xut hin ta. Lc ly ta di p sut gim. Ra ta li 4 ln, mi ln vi 5 ml nc. Sy 105 oC trong 2 n 3 gi. Ph hng ngoi (Ph lc 4.2) ca ta sy kh phi ph hp vi ph i chiu ca diclofenac. ho tan (Ph lc 11.4) Giai on trong mi trng acid: Thit b: Kiu cnh khuy. Mi trng ho tan: 900 ml dung dch acid hydrocloric 0,1 M (TT). Tc quay: 50 vng/pht. Thi gian: 2 gi. Cch tin hnh: Sau thi gian qui nh, ly vin ra khi mi trng ha tan v chuyn ngay sang thc hin Giai on trong mi trng m. Thm 20 ml dung dch natri hydroxyd 5 M (TT) vo cc th dng mi trng ha tan cn li trn, trn u, lc nu cn. o hp th ( Ph lc 4.1) ca dung dch thu c bc sng cc i khong 276 nm, mu trng l hn hp dung dch acid hydrocloric 0,1M (TT) v dung dch natri hydroxid 5 M (900 : 20). So snh vi dung dch chun c chun b nh sau: Cn chnh xc khong 68 mg diclofenac natri chun vo bnh nh mc 100 ml, thm 10 ml dung dch natri hydroxid 0,1 M, thm nc va , lc u. Ht chnh xc 2 ml dung dch ny vo mt bnh nh mc 100 ml khc, thm mu trng va n vch, lc u. Yu cu: Khng qu 10% lng diclofenac natri, C14H10Cl2NNaO2, so vi lng ghi trn nhn ha tan trong 2 gi. Giai on trong mi trng m: Thit b: Kiu cnh khuy. Mi trng ha tan: 900 ml dung dch m phosphat pH 6,8. Dung dch m phosphat pH 6,8: Ha tan 76 g natri phosphat tribasic (TT) trong va 1000 ml nc. Trn u 250 ml dung dch ny vi 750 ml dung dch acid hydrocloric 0,1 M (TT), iu chnh n pH 6,8 0,1 bng dung dch acid hydrocloric 2 M (TT) hoc dung dch natri hydroxyd 2 (TT). Tc quay: 50 vng/ pht. Thi gian: 60 pht. Cch tin hnh: Ly mt phn dung dch mi trng sau khi ha tan, lc, b 20 ml dch lc u. Pha long vi dung dch m phosphat pH 6,8 c dung dch c nng diclofenac natri khong 0,02 mg/ml. o hp th (Ph lc 4.1) ca dung dch thu c bc sng cc i khong 276 nm trong cc o dy 1 cm, dng dung dch m phosphat pH 6,8 lm mu trng. So snh vi dung dch chun c chun b nh sau: Cn chnh xc khong 68 mg diclofenac natri chun vo bnh nh mc 100 ml, thm 10 ml dung dch natri hydroxid 0,1 M, thm nc va n vch, lc u. Ht chnh xc 3,0 ml dung dch ny vo mt bnh nh mc 100 ml khc, thm dung dch m phosphat pH 6,8 va n vch, lc u. Yu cu: Khng t hn 80% lng diclofenac natri, C14H10Cl2NNaO2, so vi lng ghi trn nhn ho tan trong c hai giai on.

nh lng Cn 20 vin loi b lp bao, tnh khi lng trung bnh v nghin thnh bt mn. Cn chnh xc mt lng bt vin tng ng vi khong 50 mg diclofenac natri vo bnh nh mc 100 ml, thm 50 ml nc, lc u. Siu m 20 pht, thm nc va n vch, lc u, lc qua giy lc mn, loi b 20 ml dung dch lc u. Ly chnh xc 2 ml dung dch lc vo bnh nh mc 100 ml, thm ethanol 96% (TT) va n vch, lc u. o hp th (Ph lc 4.1) ca dung dch thu c bc sng cc i khong 282 nm trong cc o dy 1 cm, dng ethanol 96% (TT) lm mu trng. So snh vi mt dung dch chun c nng tng ng, tin hnh song song trong cng iu kin. Bo qun Trong bao b kn, ni kh mt, trnh nh sng. Loi thuc Thuc chng vim khng steroid Hm lng thng dng 25 mg, 50 mg.

Diclofenac Sodium Delayed-Release Tablets Diclofenac Sodium Delayed-Release Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of diclofenac sodium (C14H10Cl2NNaO2). Packaging and storage Preserve in tight, light-resistant containers. Identification A: The retention time of the diclofenac peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay. B: It meets the requirements of the flame test for Sodium 191 .

Unless otherwise specified in an individual monograph, prepare a solution to contain 0.1 g of the sodium compound in 2 mL of water. Add 2 mL of 15% potassium carbonate, and heat to boiling. No precipitate is formed. Add 4 mL of potassium pyroantimonate TS, and heat to boiling. Allow to cool in ice water and, if necessary, rub the inside of the test tube with a glass rod. A dense precipitate is formed. Sodium compounds impart an intense yellow color to a nonluminous flame.

Dissolution

711 Proceed as directed for Procedure for Method B under Apparatus

1 and Apparatus 2, Delayed-Release Dosage Forms.

acid stage Medium: 0.1 N hydrochloric acid; 900 mL. Apparatus 2 (paddles constructed of, or coated with, polytef being used): 50 rpm. Procedure At the end of 2 hours, remove each Tablet, or the major portion thereof if the Tablet is not intact, from the individual vessels, and subject them to the test in the Buffer stage. To the 0.1 N hydrochloric acid remaining in each vessel, add 20.0 mL of 5 N sodium hydroxide, and stir for 5 minutes. Determine the amount of C14H10Cl2NNaO2 dissolved from UV absorbances at the wavelength of maximum absorbance at about 276 nm on filtered portions of the solution under test in comparison with a Standard solution prepared as follows. Transfer about 68 mg of USP Diclofenac Sodium RS, accurately weighed, to a 100-mL volumetric flask, add 10.0 mL of 0.1 N sodium hydroxide, dilute with water to volume, and mix. Transfer 2.0 mL of this solution to a second 100-mL volumetric flask, dilute with a mixture of 0.1 N hydrochloric acid and 5 N sodium hydroxide (900:20) to volume, and mix. This Standard solution contains about 13.6 g of USP Diclofenac Sodium RS per mL. buffer stage pH 6.8 Phosphate buffer Dissolve 76 g of tribasic sodium phosphate in water to obtain 1000 mL of solution. Mix 250 mL of this solution with 750 mL of 0.1 N hydrochloric acid, and, if necessary, adjust with 2 N hydrochloric acid or 2 N sodium hydroxide to a pH of 6.8 0.05. Medium: pH 6.8 Phosphate buffer; 900 mL. Apparatus 2: 50 rpm. Procedure At the end of 45 minutes, determine the amount of C14H10Cl2NNaO2 dissolved from UV absorbances at the wavelength of maximum absorbance at about 276 nm on filtered portions of the solutions under test, suitably diluted with Medium, in comparison with a Standard solution prepared as follows. Transfer about 68 mg of USP Diclofenac Sodium RS, accurately weighed, to a 100-mL volumetric flask, add 10.0 mL of 0.1 N sodium hydroxide, dilute with water to volume, and mix. Transfer 2.0 mL of this solution to a second 100-mL volumetric flask, dilute with Medium, as obtained in the

Buffer stage, to volume, and mix. This Standard solution contains about 0.02 mg of USP Diclofenac Sodium RS per mL. Tolerances Not less than 75% (Q) of the labeled amount of C14H10Cl2NNaO2 is dissolved. Uniformity of dosage units Chromatographic purity pH 2.5 Phosphate buffer, Mobile phase, Diluent, Resolution solution, and Chromatographic system Proceed as directed in the Assay. Standard solution Prepare a solution having a known concentration of about 0.8 mg per mL of USP Diclofenac Related Compound A RS in methanol. Dilute an accurately measured volume of this stock solution with Diluent to obtain a solution having a known concentration of about 4 g per mL. Test solution Use the Assay preparation, prepared as directed in the Assay. Procedure Separately inject equal volumes (about 10 L) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses over a period of 40 minutes. Calculate the percentage of diclofenac related compound A in relation to the quantity of diclofenac sodium in the Tablets taken by the formula: 10(C/A)(rU / rS) in which C is the concentration, in g per mL, of USP Diclofenac Related Compound A RS in the Standard solution; A is the quantity, in mg, of diclofenac sodium (C14H10Cl2NNaO2) in the Tablets taken for the Assay, as determined in the Assay; and rU and rS are the diclofenac related compound A peak responses obtained from the Test solution and the Standard solution, respectively: not more than 0.5% is found. Calculate the percentage of each other impurity, other than diethyl phthalate, if present, in relation to the diclofenac sodium in the Tablets taken by the formula: 10(C/A)(ri / rS) 905 : meet the requirements.

in which ri is the peak response for each impurity obtained from the Test solution, and the other terms are as defined above: not more than 1.0% of any individual impurity is found, and not more than 1.5% of total impurities is found. Assay pH 2.5 Phosphate buffer Mix equal volumes of 0.01 M phosphoric acid and 0.01 M monobasic sodium phosphate. If necessary, adjust with additional portions of the appropriate component to a pH of 2.5 0.2. Mobile phase Prepare a filtered and degassed mixture of methanol and pH 2.5 Phosphate buffer (700:300). Make adjustments if necessary (see System Suitability under Chromatography resolution.] Diluent Prepare a mixture of methanol and water (70:30). Standard preparation Prepare a solution of USP Diclofenac Sodium RS in Diluent having a known concentration of about 0.75 mg per mL. Resolution solution Prepare a solution in Diluent containing 20 g of diethyl phthalate, 7.5 g of USP Diclofenac Related Compound A RS, and 0.75 mg of USP Diclofenac Sodium RS per mL. Assay preparation Transfer 20 Tablets to a volumetric flask of such capacity that when filled to volume, a concentration of about 0.75 mg of diclofenac sodium per mL is obtained. Add Diluent to about 70% of the capacity of the flask, and shake by mechanical means for not less than 30 minutes to disintegrate the Tablets. Cool to room temperature, dilute with Diluent to volume, and mix. Pass a portion of the solution through a filter having a 0.5-m or finer porosity, and use the filtrate as the Assay preparation. Chromatographic system (see Chromatography 621 ) The liquid chromatograph is 621 ). [noteIncreasing the proportion of buffer increases

equipped with a 254-nm detector and a 4.6-mm 25-cm column that contains packing L7 (end-capped). The flow rate is about 1 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.5 for diethyl phthalate, 0.6 for diclofenac related

compound A, and 1.0 for diclofenac; and the resolution, R, between diethyl phthalate and diclofenac related compound A is not less than 2.2, and between diclofenac related compound A and diclofenac is not less than 6.5. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%. Procedure Separately inject equal volumes (about 10 L) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the quantity, in mg, of diclofenac sodium (C14H10Cl2NNaO2) in each Tablet taken by the formula: (VC / 20)(rU / rS) in which C is the concentration, in mg per mL, of USP Diclofenac Sodium RS in the Standard preparation; V is the volume of the flask used, in mL; and rU and rS are the diclofenac peak responses obtained from the Assay preparation and the Standard preparation, respectively. Auxiliary Information Please check for your question in the FAQs before contacting USP. Topic/Question Monograph Contact Clydewyn M. Anthony, Ph.D. Scientist 1-301-816-8139 Lili Wang, Technical Services Scientist 1-301-816-8129 RSTech@usp.org (BPC05) Biopharmaceutics05 Expert Committee (MDCCA05) Monograph Development-Cough Cold and Analgesics

Reference Standards

Margareth R.C. Marques, Ph.D. Senior Scientist 1-301-816-8106 USP32NF27 Page 2124 711

Pharmacopeial Forum: Volume No. 31(3) Page 751 Chromatographic Column DICLOFENAC SODIUM DELAYED-RELEASE TABLETS Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.

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