197 11. LIST OF TABLES TABLE 2.2.1.1: COMPARISON OF DATA REQUIRED TO BE SUBMITTED IN CTD FORMAT FOR NDA, ANDA & BLA. CTD NDA: 21 CFR 314.50 ANDA: 21 CFR 314.94 (unless otherwise indicated) BLA: 21 CFR 601.2 (unless otherwise indicated) Module-1 (a) Application form (a)(1)Application form (a)Application form (c) (2) (i) annotated text of proposed (a)(2) table of contents (d) (1) (v) statement of field copy (a)(3) basis for ANDA submission (e) samples and labeling (a)(4) conditions of use (a) labels, enclosures and medication guides (h) patent information (a)(5) active ingredients 306(k)(1) and (2) debarment certification / list of convictions (FDC Act) (i) patent certification Section 306(k)(1) and (2) debarment certification / list of convictions (FDC Act) (j) claimed exclusivity (a)(6) route of administration, dosage form and strength (k) financial certification or disclosure (a)(8) labeling requirements (a)(12) patent certification (a)(13) financial certification or disclosure statement (a) financial certification or disclosure statement (d)(5) certification of field copy (a)claim of categorical exclusion or environmental assessment Module 2 a) Comprehensive table of contents N/A b) Summaries (a) Summaries c) (5)(vii) abuse potential Module 3 (d)(1) chemistry, mfg & control information (a)(9) cmc (a)full description of manufacturing methods (a)(10) samples (a) samples Module 4 (d)(2) nonclinical pharmacology & toxicology N/A (a)Data from nonclinical studies Module 5 (d)(3)human pharmacokinetics (a)(7) bioequivalence/ bioavailability information (d)(4) microbiology 320.22 (d)(2)(i) waiver of in vivo BA/BE (d)(5) clinical data (a)data from clinical studies (d)(6) statistical section (d)(7) pediatric use (f)CRF and CRT
Transcript
197
11. LIST OF TABLES
TABLE 2.2.1.1: COMPARISON OF DATA REQUIRED TO BE SUBMITTED INCTD FORMAT FOR NDA, ANDA & BLA.
TABLE 5.2.1.3: AVAILABILITY OF GENERIC MEDICINES IN PRIVATESECTOR IN INDIA
S.No.
Survey Site % medianavailability
S.No.
Survey Site % medianavailability
1 Chennai 95% 2 Haryana 50%3 Karnataka 50% 4 West Bengal 74.3%5 Maharastra
(12 distt.)66.7% 6 Maharastra
(4 Region)47.9%
204
TABLE 7.2.1: CONTENTS OF THE QUESTIONNAIRE POSED TOPRESCRIBERS
S. No. Questions Options
1 Do you prescribe generic medicines to the patients? Y/N
2 Do you prescribe generic medicines in routine or to poorpatients only?
Routine/Poor
3 Do you consider generic drugs at par with the brandeddrugs as far as their therapeutic efficacy is concerned?
Y/N
4 Are you aware that generics as well as branded drugs haveto pass the same quality tests w. r. t. their identity, purity &strength before coming to the market?
Y/N
5 Do you know that generics and branded drugs are regulatedby the same law for their quality, price structure etc.?
Y/N
6. Do you know that generics are much cheaper than branded? Y/N
7. What is the reason for low prices of generics? Less effective Poor quality Poor raw material No sale promotion
8. Any experiences with generics. No effects Side effects Less effective
9. Do you prefer generic drugs to branded drugs? Y/N
10. Which type of drugs do you use for your own/family use Branded/Generic
TABLE 7.2.2: GENERIC PRESCRIPTION
S. No. Particulars %age
1 % of doctors who prescribe generics. 58.8
2 % of doctors who never prescribe generics. 41.2
3 % of doctors who prescribe generics only to poor patients. 37
4 % of doctors who prescribe generics in routine. 17.8
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TABLE 7.2.3: QUALITY PERCEPTIONS AMONG DOCTORS
S.No.
Particulars %age
1 % of doctors who prescribe generics (237) &consider their qualityat par with branded.
60
2 % of doctors who never prescribe generics (166) & consider thatthe quality of generics is not at par with branded.
75
3 % of doctors who prescribe generics to their patients (237) & alsoprefer to use generics for own family also.
11.6
4 % of doctors who prescribe generics to their patients (237), butprefer branded for their family.
63
5 % of doctors who prescribe generics to poor (148) also prefers touse them for their family.
4.7
6 % of doctors who prefer generics for their family members. 7
7 % of doctors who prefer branded medicines for own use. 75
TABLE 7.2.4: GENERIC PRESCRIPTION BY DOCTORS(GOVERNMENT v/s PRIVATE DOCTORS)
S. No. Particulars % age1 % of surveyed doctors who prescribe generics. 58.8
2 % of government doctors who prescribe generics. 76.2
3 % of private doctors who prescribe generics. 52.7
TABLE 7.2.5:ADVERSE EXPERIENCES WITH GENERICS
S. No. Particulars %age
1 % of doctors who experienced side effects with generics. 10.3
2 % of doctors who found no therapeutic effect with generics. 2.1
3 % of doctors who found generics less effective to branded. 29.5
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TABLE 7.2.6: REASONS FOR USING GENERIC MEDICINES-CONSUMER’SPERCEPTIONS ABOUT GENERICS IN MALAYSIA
S.No. Reasons for using generics % age
1 Know it is the same and will work well 40
2 Cheaper 36
3 Given at hospital 21
4 Used before and it worked well 11
5 Just to give it a try 9
6 Recommended by someone 5
7 Other reasons 6
TABLE 7.3.1: QUESIONNAIRE POSED TO DISPENSING PHARMACISTS
S. No. Questions Options1 Do you stock or sell generic/generic branded medicines? Yes/No
2 What is the average percentage of generic prescriptions? %
3 Do you sell branded drugs at printed MRP or less? % less
4 Do you sell generic/branded generics at printed MRP orless?
% less
5 How much is the stocks of generic/ branded generic drugs inthe shop?
%
6 What is the volume of sale of generic/branded genericdrugs?
%
7 What is the average profit margin being earned in sale ofbranded drug?
%
8 What is the average profit margin being earned in sale ofgeneric/branded generic drugs?
%
9 Do you know that branded, generic and branded-genericdrugs have same quality standards?
Yes/No
10 Do you know that generics/branded generics are at par inquality with branded?
Yes/No
11 Which type of drugs you will use for own use? Branded/generic
12 Do you advocate generic prescription only? Yes/ No
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TABLE 7.3.2: PROFIT MARGINS FOR GENERIC AND BRANDED DRUGSFOR RETAILERS
S.No. Branded Generic
1 % chemists found selling medicines at M.R.P 35% 5%
2 Discount offered by the chemist to the consumer 5-15% 40-70%
3 Average profit margins to the chemist 10-20% 15-70%
4 Preference for own use 20% 50%
TABLE 7.4.1: COMPARATIVE PRICE STRUCTURE OF MEDICINESAVAILABLE AT 24 x 7 JAN AUSHADHI STORES ANDAVERAGE MARKET PRICES
S.No.
Name of medicine Strength Pack JanAushadhiPrice(Rs.)
Averagemarket Price(Rs.)
1. Ciprofloxacin tablet 250 mg 10 11.10 55.00
2. Ciprofloxacin tablet 500 mg 10 21.50 97.00
3. Diclofenac tablet 100mg 10 3.35 36.70
4. Cetirizine tablet 10mg 10 2.75 20.00
5. Paracetamol tablet 500 mg 10 2.45 10.00
6. Nimesulide tablet 100 mg 10 2.70 25.00
7. Cough syrup 110 ml 110ml 13.30 33.00
208
TABLE 8.1.1: COMPARATIVE PRICE STRUCTURE OF BRANDED ANDSOME BRANDED-GENERIC MEDICINES WITH MARK UPS
S.No
Brand / tradeName ofMedicine
INN Name,Strength &Dosage form
Manu-facturer
PTR(1x10)
MRP(1x10)
Mark-up(Retailer)
1 Alerid tablets(B)
Cetirizine Hcl10mg/tab
Cipla Rs.27.16
Rs.35.31
30 %
Cetcip tablets(B/G)
Rs.2.24
Rs.25.00
1016%
2 Fludac capsules(B)
Fluoxetine20mg/cap
Cadila Rs.29.80
Rs.37.26
25 %
Cadflo capsules(B/G)
Rs.6.00
Rs.28.00
367 %
3 Ciprobid tablets(B)
Ciprofloxacin500mg/tab
Cadila Rs.54.84
Rs.68.56
27 %
Ciprodac tablets(B/G)
Rs.15.00
Rs.68.56
357 %
4 Lanzol-30capsules (B)
Lansoprazole30mg/cap
Cipla Rs.42.36
Rs.53.77
27 %
Lansec-30capsules (B/G)
Rs.15.68
Rs.47.25
201 %
5 Restyl tablets(B)
Alprazolam0.25mg/tab
Cipla Rs.11.85
Rs.14.82
25 %
Tranex tablets(B/G)
Rs.2.20
Rs.11.34
415%
Branded medicine (B) Branded-generic medicine (B/G)Price to the retailer (PTR) Maximum Retail Price (MRP)
209
TABLE 8.1.2: COMPARATIVE ANALYTICAL EVALUATION OF SOME BRANDED AND BRANDED -GENERICDRUG PRODUCTS
S.No
QualityParameter
Restyl TabletsB.N.D-82796Mfg. Cipla Ltd.
Tranex TabletsB.N.BW-8006Mfg. Cipla Ltd.
Alerid TabletsB.N.D-72641Mfg. Cipla Ltd.
Cetcip TabletsB.N.DF-8183Mfg. Cipla Ltd.
Ciprobid TabletsZHH-1552Mfg. ZydusCadila.
Ciprodac TabletsB.N.JK-8021Mfg. Cadila Ltd.
1 Identification Complies Complies Complies Complies Complies Complies2 Uniformity of
Investigational New Drug/ New DrugApplication to conduct clinical trials (form 44)
Clinical Trials Phase IClinical Trials Phase IIClinical Trials Phase III
Application to manufacture New Drug (on form 44) Submission to DCGI Review by DCGI Approval in form 46/46A
Application for approval to manufacture a New Drug to SLAwith DCGI approval on form 46/46A Submission to SLA Review by SLA Pre-approval plant inspection Approval by SLA
Post marketing Surveillance Adverse Reaction reporting Approval of label, carton & package insert.
215
Within 30 days after sealing IND date
FIGURE 2.1.1.1: INVESTIGATIONAL NEW DRUG APPROVAL PROCESS
Application send for review to reviewer
Announce to conductclinical trial
Submit report of clinical trials
Meeting to conduct phase-IIIclinical trials
Phase-III clinical trialscommence
Pre-NDA meeting
-ve
Within 60 days from INDannouncing date
Before 1 month from ending ofphase-II clinical trials
+ve or no response
Before 9-12 month from NDAsubmission
215
Within 30 days after sealing IND date
FIGURE 2.1.1.1: INVESTIGATIONAL NEW DRUG APPROVAL PROCESS
Applicant
Filing IND
Application to FDA
Application send for review to reviewer
Review Report
Announce to conductclinical trial
Submit report of clinical trials
Meeting to conduct phase-IIIclinical trials
Phase-III clinical trialscommence
Pre-NDA meeting
-ve
Within 60 days from INDannouncing date
Before 1 month from ending ofphase-II clinical trials
+ve or no response
Before 9-12 month from NDAsubmission
215
Within 30 days after sealing IND date
FIGURE 2.1.1.1: INVESTIGATIONAL NEW DRUG APPROVAL PROCESS
Application send for review to reviewer
-ve
Within 60 days from INDannouncing date
Before 1 month from ending ofphase-II clinical trials
+ve or no response
Before 9-12 month from NDAsubmission
216
FIGURE 2.2.1.1: NDA APPROVAL AND REVIEW PROCESS
Filing NDA to FDA
Send to appropriate ReviewDivision of FDA
Check Fileability ofApplication
If Application FileableInform theApplicant
Send toReviewer
No Yes
Submit ReviewReport CDER
Deficiency letteris issued
If NegativeWithin 120 days
If Positive
Market AuthorisationIssued
Applicant inform itsintention to amend or not
amend the application
Applicant submitsappended application toFDA & FDA review the
amended application
Review Report
Refusal to Applicant
Within 120 days
If Negative
If Positive
217
FIGURE 4.3.1: ANDA PATENT CERTIFICATION OPTIONS
ANDA PatentCertification Options
Paragraph-INo Patent
Information hasbeen filed
Paragraph-II
Patent hasExpired
Paragraph-IIIPatent has not expired
but will expire on aparticular date
Paragraph-IVPatent is invalid or non-
infringed by genericapplicant
FDA may approve ANDAimmediately; one or more
generic applicants may enter
Generic applicant providesnotice to the patent holderand NDA filer, entry of the
first filer may not occur.
FDA may approve ANDAimmediately; one or more
generic applicants may enter
FDA may approve ANDAeffective on the day that thepatent expires; one or moregeneric applicant may enter
218
FIGURE 4.3.2: PARAGRAPH IV CERTIFICATION
PARAGRAPH IV
CERTIFICATIONPatent holder does not sue; the FDA may approve theANDA assuming other regulatory conditions are
fulfilled
Generic applicant mayenter
Patent holder sue generic applicant within 45 days;trigger of automatic 30- month stay
30- month
stay not expired
If court decides in brandname company’s favor,the FDA can’t approve
ANDA till patent expires
No generic entry tillexpiry of patent
If court decides ingeneric applicant’sfavor, the FDA can
approve ANDA and 180days exclusivity period
begins
First generic applicant mayenter; subsequent generic
applicants may only beapproved after the first generic
applicant’s 180 days haveexpired
Patent expire; the FDAcan approve ANDA (No
180 days exclusivity)
One or more genericmay enter
30- month stay expired;the FDA may be able to
approve ANDA
For the first generic applicant the 180 daysexclusivity period begins upon marketingor court decision, whichever comes first
Subsequent generic applicants may only beapproved after the first generic applicant’s 180 days
have expired
219
FIGURE 4.3.3: GENERIC DRUG REVIEW & APPROVAL PROCESS IN US
No No
Ok Ok
Yes No
APPLICANT / ANDA
Complete Incomplete Refuse to file letterissued
Review by OGD/CDER
BioequivalenceReview
LabelingReview
Plant Inspectionrequest
Chemistry /Micro Review
BioequivalenceReview Acceptable
Chemistry / MicroReview Acceptable
BioequivalenceDeficiency Letter Not Approval
Letter
Pre-ApprovalPlant Inspection
Acceptable
Tentative ANDAApproval
Approval deferred pendingsatisfactory results
220
FIGURE: 4.4.1: VISUAL IDENTITY FOR GENERICS IN BRAZIL
FIGURE 4.4.2: VISUAL IDENTITY FOR GENERICS IN BRAZIL
221
FIGURE 4.7.1: SETTING PRICE LEVELS
FIGURE 4.7.2: ESTABLISHING THE REFERENCE PRICE USINGMEDICINE CLASSIFICATION
222
FIGURE 4.7.3: ESTABLISHING THE REFERENCE PRICES USING PRICEMEASURES
FIGURE 4.7.4: CALCULATION OF PATIENT CO-PAYMENT
223
FIGURE 4.7.5: INN PRESCRIBING
FIGURE 7.2.1: PATTERN OF PRESCRIBING GENERIC MEDICINES
A: % of Physicians preferred only generic medicines for family use
B: % of Physicians preferred both types of medicines for family use
C: % of Physicians preferred only branded medicines for family use
01020304050607080
A
Percentage
223
FIGURE 4.7.5: INN PRESCRIBING
FIGURE 7.2.1: PATTERN OF PRESCRIBING GENERIC MEDICINES
A: % of Physicians preferred only generic medicines for family use
B: % of Physicians preferred both types of medicines for family use
C: % of Physicians preferred only branded medicines for family use
A B C
223
FIGURE 4.7.5: INN PRESCRIBING
FIGURE 7.2.1: PATTERN OF PRESCRIBING GENERIC MEDICINES
A: % of Physicians preferred only generic medicines for family use
B: % of Physicians preferred both types of medicines for family use
C: % of Physicians preferred only branded medicines for family use
224
FIGURE 7.3.1: PERCEPTIONS OF DISPENSING PHARMACISTSREGARDING GENERIC AND BRANDED MEDICINES(PREFERENCE FOR OWN USE)
FIGURE 7.3.2: PERCEPTIONS ABOUT QUALITY OF GENERICS VIS-À-VIS-BRANDED MEDICINES AMONG DISPENSINGCHEMISTS.
A-- Advocate generic prescription
B-- Know that statutory quality standards for generic and branded are same.
C-- Know that quality of generic and branded are same
05101520253035404550
Branded
Percentage
0
20
40
60
80
100
Percentage
224
FIGURE 7.3.1: PERCEPTIONS OF DISPENSING PHARMACISTSREGARDING GENERIC AND BRANDED MEDICINES(PREFERENCE FOR OWN USE)
FIGURE 7.3.2: PERCEPTIONS ABOUT QUALITY OF GENERICS VIS-À-VIS-BRANDED MEDICINES AMONG DISPENSINGCHEMISTS.
A-- Advocate generic prescription
B-- Know that statutory quality standards for generic and branded are same.
C-- Know that quality of generic and branded are same
Branded Both Generic
A B C
224
FIGURE 7.3.1: PERCEPTIONS OF DISPENSING PHARMACISTSREGARDING GENERIC AND BRANDED MEDICINES(PREFERENCE FOR OWN USE)
FIGURE 7.3.2: PERCEPTIONS ABOUT QUALITY OF GENERICS VIS-À-VIS-BRANDED MEDICINES AMONG DISPENSINGCHEMISTS.
A-- Advocate generic prescription
B-- Know that statutory quality standards for generic and branded are same.
C-- Know that quality of generic and branded are same
225
13. TESTING METHODS - ANNEXURE-1
TEST METHOD FOR ALPRAZOLAM TABLET I.P.
Identification: In the Assay, the principal peak in the chromatogram obtained with the
test solution corresponds to the peak in the chromatogram obtained with the reference
solution.
Uniformity of weight: Weigh individually 20 units selected at random and calculate the
average weight. Not more than two of the individual weights deviate from the average
weight by more than 7.5% and none deviate by more than 15%
Uniformity of content: The test for uniformity of content is based on the assay of the
individual contents of active substance(s) of a number of single dose units to determine
whether the individual contents are within limits set with reference to the average content
of the sample.
Determine the content of active ingredient (s) in each of 10 dosage units taken at random
using the method which is used for assay. The preparation complies with the test if each
individual content is 85 to 115 percent of the average content. The preparation fails to
comply with the test if more than one individual content is outside these limits or if one
individual content is outside the limits of 75 to 125 percent of the average content.
Determine the content of active ingredient by liquid chromatography.
Test solution: Transfer one tablet to a container, add 0.4 ml of water on to the tablet,
allow the tablet to stand for 2 minutes and swirl the container to disperse the tablet. Add
sufficient Acetonitrile to produce a solution containing 0.0025 per cent w/v of
Alprazolam. Shake to mix and centrifuge, if necessary.
Reference solution: A solution containing 0.0025 per cent w/v of Alprazolam RS in
Acetonitrile.
Chromatographic system:–
Column: a stainless steel column 25 cm x 4.6 mm, packed with porous silica
particles, 5 to 10 μm in diameter,
226
Mobile phase: a mixture of 850 volumes of acetonitrile, 80 volumes of chloroform,
50 volumes of 1-butanol, 20 volumes of water and 0.5 volume of glacial acetic
acid.
Flow rate. 2 ml per minute,
Detector: spectrophotometer set at 254 nm,
Injection volume:a 10 μl or 20 μl loop injector.
Calculate the content of C17H13ClN4 in the tablet.
Assay: Determine contents of Alprazolam by liquid chromatography.
Test solution: Place 5 tablets in a flask, add 2 ml of water and swirl to disperse the tablets.
Add sufficient Acetonitrile to produce 25.0 ml. Shake for 10 to 15 minutes and centrifuge
if necessary. Dilute a portion of the clear solution with Acetonitrile to produce a solution
containing 0.0025 per cent w/v of Alprazolam.
Reference solution: A 0.0025 per cent w/v solution of Alprazolam RS in acetonitrile.
Chromatographic system as described under Uniformity of content.
Inject the reference solution. The test is not valid unless the relative standard deviation for
replicate injections is not more than 2.0 per cent. Inject alternately the test solution and the
reference solution. Calculate the content of C17H13ClN4 in the tablets.
227
TEST METHOD FOR CETIRIZINE TABLET I.P.
Identification: In the Assay, the principal peak in the chromatogram obtained with the test solution
corresponds to the peak in the chromatogram obtained with the reference solution.
Uniformity of weight: Weigh individually 20 units selected at random and calculate the
average weight. Not more than two of the individual weights deviate from the average
weight by more than 7.5% and none deviate by more than 15%
Uniformity of content: The test for uniformity of content is based on the assay of the
individual contents of active substance(s) of a number of single dose units to determine
whether the individual contents are within limits set with reference to the average content
of the sample.
Determine the content of active ingredient (s) in each of 10 dosage units taken at random
using the method which is used for assay. The preparation complies with the test if each
individual content is 85 to 115 percent of the average content. The preparation fails to
comply the test if more than one individual content is outside these limits or if one
individual content is outside the limits of 75 to 125 percent of the average content.
Determine the content of each dosage unit by liquid chromatography as described under
Assay, using the following solution as the test solution. Test solution: Disperse 1 tablet in
the mobile phase, mix and dilute to 100.0 ml with the mobile phase, filter. Dilute 5.0 ml of
the solution to 10.0 ml with mobile phase.
Dissolution Test: Perform dissolution test using Apparatus No.1as provided under chapter
2.5.2 of I.P.2007
Medium: 900 ml of 0.1 M hydrochloric acid.
Speed and time: 100 rpm and 45 minutes.
Withdraw a suitable volume of the medium and filter. Measure the absorbance of the
filtrate, suitably diluted with the dissolution medium if necessary, at the maximum at
about 230 nm using spectrophotometer. Calculate the content of C21H25ClN2O3.2HCl in
the medium from the absorbance obtained from a solution of known concentration of
cetirizine hydrochloride RS in the same medium.
228
Assay: Determine the contents of Cetirizine Hydrochloride by liquid chromatography.
Test solution: Weigh and powder 20 tablets. Weigh accurately a quantity of the powder
containing about 25 mg of Cetirizine Hydrochloride, add the mobile phase, mix and dilute
to 50.0 ml with the mobile phase, filter. Dilute 1.0 ml of the solution to 10.0 ml with
mobile phase.
Reference solution: A 0.05 per cent w/v solution of cetirizine hydrochloride RS in the
mobile phase. Dilute 1.0 ml of the solution to 10.0 ml with the mobile phase.
Chromatographic system:–
Column: a stainless steel column 25 cm x 4.6 mm, packed with octadecysilane
bonded to porous silica (5 μm),
Mobile phase: a mixture of 0.4 volume of dilute sulphuric acid, 6.6 volumes of
water and 93 volumes of acetonitrile,
Flow rate: 1.2 ml per minute,
Detector:spectrophotometer set at 230 nm,
Injection volume:a 20 μl loop injector.
229
TEST METHOD FOR CIPROFLOXACIN TABLET I.P.
Identification: A. In the Assay, the principal peak in the chromatogram obtained with the
test solution corresponds to the peak in the chromatogram obtained with the reference
solution.
B. Determine by thin-layer chromatography, coating the plate with silica gel G. Place the
plate in an atmosphere of ammonia for about 15 minutes and transfer it to an unsaturated
chamber.
Mobile phase: A mixture of 40 volumes of dichloromethane, 40 volumes of methanol, 20
volumes of strong ammonia solution and 10 volumes of acetonitrile.
Test solution: Shake a quantity of the powdered tablets containing about 0.15 g of
ciprofloxacin with 75 ml of water for 20 minutes, dilute to 100.0 ml with water, mix,
centrifuge, and use the clear supernatant liquid.
Reference solution: A 0.15 per cent w/v solution of ciprofloxacin hydrochloride RS in
water. Apply to the plate, as 1-cm bands, 5 μl of each solution. Place the plate in an
atmosphere of ammonia for about 15 minutes and transfer it to an unsaturated chamber
containing the mobile phase. Allow the mobile phase to rise 12 cm. Dry the plate in air for
15 minutes and examine in ultraviolet light at 254 nm and at 365 nm. The principal band
in the chromatogram obtained with the test solution corresponds to that in the
chromatogram obtained with the reference solution.
Dissolution Test: Perform dissolution test using Apparatus. No 1 as provided under
Chapter 2.5.2 of I.P.2007
Medium: 900 ml of water
Speed and time: 50 rpm and 30 minutes.
Withdraw a suitable volume of the medium and filter. Measure the absorbance of the
filtrate, suitably diluted with water if necessary, at the maximum at about 276 nm (2.4.7).
Calculate the content of ciprofloxacin, C17H18FN3O3, in the medium from the
absorbance obtained by repeating the determination using a solution of known
concentration of Ciprofloxacin Hydrochloride RS.
230
Assay: Determine contents of Ciprofloxacin Hydrochloride by liquid chromatography.
Test solution: Weigh and powder 20 tablets. Weigh accurately a quantity of the powder
containing about 1.25 g of Ciprofloxacin, add about 400 ml of 0.01 M hydrochloric acid,
shake for 20 minutes, dilute to 500.0 ml with 0.01 M hydrochloric acid and filter. Dilute
10.0 ml of the filtrate to 100.0 ml with 0.01 M hydrochloric acid.
Reference solution (a): A 0.03 per cent w/v solution of Ciprofloxacin hydrochloride RS
in 0.01 M hydrochloric acid.
Reference solution (b): A 0.05 per cent w/v solution of Ciprofloxacin ethylenediamine
analog RS in water.
Chromatographic system:
Column: a stainless steel column 25 cm x 4 mm, packed with octadecylsilyl silica
gel (5 μm),
Mobile phase: a mixture of 87 volumes of 0.025 M phosphoric acid, previously
adjusted with triethylamine to a pH of 3.0 ± 0.1, and 13 volumes of acetonitrile,
Flow rate: 1.5 ml per minute,
Column temperature. 30° ± 1°,
Detector: spectrophotometer set at 278 nm,
Injection volume a 10 μl loop injector.
Inject reference solution (b) and record the chromatogram adjusting the sensitivity
and flow rate suitably so that the retention time for ciprofloxacin is between 6.4 and 10.8
minutes, the relative retention times are about 0.7 for ciprofloxacin ethylenediamine
analog and 1.0 for ciprofloxacin and the resolution between ciprofloxacin ethylenediamine
analog peak and ciprofloxacin peak is not less than 6. The column efficiency, determined
from ciprofloxacin peak, is not less than 2500 theoretical plates, the tailing factor for the
ciprofloxacin peak is not more than 4.0 and the relative standard deviation for replicate
injections is not more than 1.5 per cent. Inject alternately the test solution and reference
solution (a).
231
TEST METHOD FOR LANSOPRAZOLE CAPSULES 30mg
Identification: A: In the Assay, the retention time in the chromatogram obtained with the
test solution corresponds to the peak in the chromatogram obtained with the standard
preparation.
B: Ultraviolet Absorption
Uniformity of weight: Weigh individually 20 units selected at random and calculate the
average weight. Not more than two of the individual weights deviate from the average
weight by more than 7.5% and none deviate by more than 15%
Dissolution Test: Perform dissolution test using Apparatus No.2 as provided under
chapter 711 of USP 30 using acidic and buffer media as prescribed below.
Medium: 0.1 N Hcl
Speed and time: 75 rpm and 60 minutes.
ACID STAGE MEDIUM
Procedure: Withdraw a 25 ml of aliquot and filter. Determine the content of
C16H14F3N3O2S dissolved in the medium by using UV absorption method at the
wavelength of maximum absorption at about 306 nm using acid stage medium as blank.
Concomitantly determine the absorption of the acid stage test solution in comparison with
a standard solution of Lansoprazole having a known conc. Equivalent to about 8% of the
labeled amount of Lansoprazole dissolved per 500 ml of acid stage medium.[A volume of
methanol not to exceed 0.5% of the total volume of the standard solution may be used to
dissolve standard Lansoprazole prior to dilution with acid stage medium].
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