“DEVELOPMENT AND VALIDATION OF NOVEL ANALYTICAL METHODS FOR THE SIMULTANEOUS ESTIMATION OF ALOGLIPTIN AND PIOGLITAZONE IN BULK DRUG AND PHARMACEUTICAL FORMULATIONS”
SYNOPSIS FOR
M.PHARM DISSERTATION
SUBMITED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE.
BY
ANUSHA M
M.PHARM, PART-1
DEPARTMENT OF PHARMACEUTICAL ANALYSIS,
NATIONAL COLLEGE OF PHARMACY,
BALRAJ-URS ROAD,
SHIMOGA-577201,
KARNATAKA, INDIA
(2013-2014)
UNDER THE GUIDANCE OF
MR. MANZOOR AHMED
ASSISTANT PROFESSOR
DEPARTMENT OF PHARMACEUTICAL ANALYSIS,
NATIONAL COLLEGE OF PHARMACY,
BALRAJ-URS ROAD,
SHIMOGA-577201 ,
KARNATAKA, INDIA.
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE.
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / Name of the candidate and address: / ANUSHA MDepartment of Pharmaceutical Analysis,
National College of Pharmacy,
Balraj Urs Road,
Shimoga-577201.
Karnataka
Permanent address
Anusha M
D/o Mahabala udupa,
Keshavapura,
Konandur(via)
Thirthahalli(tq)
Shimoga(dist)
Karnataka.
2. / Name of the institution: / National College of Pharmacy,
Balraj Urs Road,
Shimoga-577201,
Karnataka.
3. / Course of study and subject: / MASTER OF PHARMACY IN PHARMACEUTICAL ANALYSIS
4. / Date of admission: / 1/08/2013
5. / Title of the topic:
“DEVELOPMENT AND VALIDATION OF NOVEL ANALYTICAL METHODS FOR THE SIMULTANEOUS ESTIMATION OF ALOGLIPTIN AND PIOGLITAZONE IN BULK DRUG AND PHARMACEUTICAL FORMULATIONS”
6. BRIEF RESUME OF THE INTENDED WORK:
6.1. Need for the study:
Multi-ingredients formulations are useful in management of various ailments where in the intake of large number of dosage is avoided.
Alogliptin is an orally administered anti-diabetic drug in the DPP-4 inhibitor class(1). Alogliptin inhibits dipeptidyl peptidase 4 (DPP-4), which normally degrades the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide 1 ( GLP-1). The inhibition of DPP-4 increases the amount of active plasma incretins which helps with glycemic control. It is not an official drug in any Pharmacopoeia. Only one liquid chromatographic method has been reported for the estimation of Alogliptin individually(2). No other methods are available for individual drug and in any combination.
Pioglitazone is a antihyperglycemic drug belongs to the drug class of thiazolidinedione, which is used todecrease insulin resistance(3-6). It is an antidiabetic agent tomanageNIDDM (non-insulin-dependent diabetes mellitus,sugar diabetes) called type 2 diabetes.. Pioglitazone acts as an agonist at peroxisome proliferator activated receptors (PPAR) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. It is an official drug in IP(7). There are very few reports on analytical methods for estimation of Pioglitazone individually and in other combination which includes bioanalytical methods using human plasma(8,9) and rat plasma(10), RP-HPLC (11-15), Spectrophotometric(16-19) methods.
The combination of Alogliptin and Pioglitazone is very useful in the treatment of type 2 diabetes .Alogliptin and Pioglitazone are oral diabetes medicines that helps control blood sugar levels.
On literature survey, it was found that no method could be found for the simultaneous estimation of Alogliptin and Pioglitazone in combined dosage forms and no method is available in the pharmacopoeias. In the view of the need for a suitable method for routine analysis in combined formulations, attempts are being made to develop simple precise and accurate analytical methods for simultaneous estimation of titled drugs and extend it for their determination in formulation. As chromatographic methods of analysis is a pre-requisit for the marketing of most of the formulation, one RP-HPLC, HPTLC, stability indicating RP-HPLC along with Spectrophotometric methods namely simultaneous equation method (Vierodt’s method), derivative spectrophotometeric metod, Q absorbance ratio method and area under the curve method are planed to develop and validate for the simultaneous estimation of titled drugs.
Analytical validation is the corner stone of process validation.Without a proven measurement system it is impossible to confirm whether the manufacturing process has done what it purport to do. Hence, there is a need to validate the new methods developed.
6.2 DRUG PROFILE:
ALOGLIPTIN BENZOATE
IUPAC Name : 2-({6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxo-
3,4dihydropyrimidin-1(2H)-yl}methyl)benzonitrile
monobenzoate
Molecular formula : C18H21N5O2•C7H6O2
Molecular weight : 461.51 gm/mol.
Category : Hypoglycemic Agents, Antidiabetic.
PIOGLITAZONE HYDROCHLORIDE
IUPAC Name : (±)-5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-
thiazolidinedione monohydrochloride
Molecular formula : C19H20N2O3SHCl
Molecular weight : 392.90 gm/mol.
Category : Hypoglycemic Agents, Thazolidinediones.
6.3 REVIEW OF LITERATURE:
· Drug bank:alogliptin(1)
· Ramzia I E. et al. Liquid chromatographic determination of Alogliptin in Bulk and in its Pharmaceutical Preparation(2)
· Goodman,Gilman.The Pharmacological basis of Therapeutics(3)
· The Merck Index- an encyclopedia of chemicals, Drugs and Biologicals(4)
· Wilson and Gisvold’s textbook of Organic Medicinal & Pharmaceutical Chemistry(5)
· Martindale The Complete Drug References(6)
· Indian Pharmacopoeia(7)
· Effat S. et al. Developed and Validated a Simple and Rapid HPLC Method for Determination of Pioglitazone in human plasma and its application to a pharmacokinetic study(8)
· Vijaya K K. Reported Simultaneous determination of Pioglitazone and Candesartan in human plasma by LC-MS/MS and its application to a human pharmacokinetic study(9)
· Lakshmi K S. et al. Determined Pioglitazone and Glimepiride in pharmaceutical formulations and rat plasma by RP-LC(10)
· Srinivasulu D. Developed and validated a new RP-HPLC method for determination of Pioglitazone hydrochloride in pharmaceutical dosage forms(11)
· Adukondalu D. et al. Reported and validated HPLC method for detection of Pioglitazone hydrochloride in dosage forms (12)
· Venkat S. et al. Estimated Metformin Hydrochloride and Pioglitazone Hcl in their bulk and formulation dosage forms by using RP-HPLC method (13)
· Alekhya P. et al. Reported Novel RP-HPLC method for Metformin and Pioglitazone drugs in pure and pharmaceutical dosage forms(14)
· Phanikumar V. et al. Simultaneously determined Clopidogrel and Pioglitazone by high performance liquid chromatography in bulk drug and dosage forms(15)
· Jayesh D. Reported the spectrophotometric method for the simultaneous estimation of Pioglitazone and Metformin(16)
· Lalit K. et al. Estimated Pioglitazone and Glimipride in its pharmaceutical dosage form by spectrophotometric methods (17)
· Freddy H H. Reported Simultaneous estimation of Metformin hydrochloride, Rosiglitazone and Pioglitazone hydrochloride in the tablets dosage form (18)
· Sireesha M. et al. Developed and validated spectrophotometric methods for
determination of Rosiglitazone and Pioglitazone with 2, 4-dnp(19)
6.4 OBJECTIVES OF THE STUDY:
This study makes an attempt to establish sensitive and accurate methods for the estimation of Alogliptin and Pioglitazone in bulk drug and pharmaceutical dosage form.
In proposed work an attempt shall be made to:
· Develop RP-HPLC, Stability indicating RP-HPLC and HPTLC method for the simultaneous estimation of Alogliptin and Pioglitazone in combined dosage form.
· Develop new analytical method for the simultaneous estimation of Alogliptin and Pioglitazone preferably by spectrophotometeric methods like first and second order derivative, Q-absorbance ratio, simultaneous equation method and area under the curve method.
· Validate the proposed method in accordance with BP, USP and ICH guidelines for the intended analytical application.
· Apply the proposed method for the analysis of drugs in their bulk and pharmaceutical dosage form.
7. Materials and Methods:
7.1 Source of Data:
· Literature survey was done in National College of Pharmacy using internet facilities
(RGUHS HELINET) and at Library.
· Library Kuvempu University, Shimoga.
· I.I.Sc Library, Bangalore.
· RGUHS Library, Bangalore.
7.2 Method of collection of data:
For the present investigation of the new analytical methods for simultaneous estimation of Alogliptin and Pioglitazone.We are in need of Shimadzu 1700 double beam Spectrophotometer, HPLC (UFLC, shimadzu, LC-20AD, SPD-20AD), other Chromatographic instruments and volumetric glass apparatus which are available in the lab of pharmaceutical analysis department, National college of pharmacy. Shimoga.
Journals:
1) Indian journal of pharmaceutical sciences.
2) Indian drugs .
3) Indian journal of analytical chemistry and analyst.
4) Indian journal of Research in Pharmacy and Biotechnology.
5) International journal of biomedical science.
6) Journal of Pharmaceutical and biomedical analysis.
7) Analytical Chemica Acta.
7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS
TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS?
------NO ------
7.4 HAS ETHICAL CLEARENCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3?
------NOT APPLICABLE------
8.REFERENCES:
1. http://www.drugbank.ca/drugs/DB06203/2013/ November.
2. Ramzia I E, Ehab F E, Bassam M A. Liquid chromatographic determination of Alogliptin in bulk and in its pharmaceutical preparation. Int J Biomed Sc, September 2012;8( 3):215-8.
3. Laurene B, Jhon S L, keith L.P. Goodman and Gilman’s the pharmacological Basis of Therapeutics; Mc Graw Hill, Newyork, U.S.A; 2006; 11: p. 1510.
4. O’Neil M J. The Merk Index- an encyclopedia of chemicals, Drugs and Biologicals, New Jersy, Merk and co., INC; 13:p. 7533,1335.
5. John H.B, John M.B. Wilson and Gisvold’s textbook of Organic Medicinal & Pharmaceutical Chemistry, Lippincott Williams & Wilkins , Wolters Kluner Company; 2004;11: p. 672
6. Sean C S, Martindale the Complete references; Pharmaceutical Press, 1 lambeth
High Street,London SEI 7 IN, UK; 2002; 33:p. 333.3.
7. Indian Pharmacopoeia 2010(2):1916.
8. Effat S, Hassan J, Shahrooz S. Development and Validation of Simple and Rapid HPLC Method for determination of Pioglitazone in human plasma and its application to a pharmacokinetic Study. j Chromatographic Science. October 2008;46:809-12.
9. Vijaya K K, Nageswara R P, Jaswanth K I, Seshagiri R. Simultaneous determination of pioglitazone and candesartan in human plasma by LC-MS/MS and its application to a human pharmacokinetic study. J pharmaceutical analysis. June 2012;2(3):167-73.
10. Lakshmi K S, Rajesh T, Shrinivas S. Determination of pioglitazone and glimepiride in pharmaceutical formulations and rat plasma. Int J PharmTech Res.july-september 2009;1(3):496-9.
11. Srinivasulu D, Sastry B S, Omprakash. Developed and validated a new RP-HPLC method for determination of pioglitazone hydrochloride in pharmaceutical dosage forms . Int J Chem Res. May 2010;1(1):18-20.
12. Adukondalu D, Malathyl P S, Venkateshwar R J, Madhusudan R Y. Development and validation of HPLC method for detection of pioglitazone hydrochloride in dosage forms. Int J Pharm Bio Sci. oct-dec 2011;1( 4):474-8.
13. Venkat S R, Sankara R G, Gopala Krishna A, Ameer K, Chandrasekar K. Estimation of Metformin Hydrochloride and Pioglitazone Hydrochloride in their bulk and formulation Dosage forms by using RPHPLC Method. Orient. J Chem . june 2011; 27(3):1221-6.
14. Alekhya P, Aneesha A. Novel RP-HPLC method development and validation of Metformin and Pioglitazone drugs in pure and pharmaceutical dosage forms. Indian J of Research in Pharmacy and Biotechnology. Oct 2013;1(5):711-6.
15. Phani K V, Sunandamma Y. Simultaneous determination of Clopidogrel and Pioglitazone by high performance liquid chromatography in bulk drug and dosage forms. Int J of Pharmaceutical and Life Sciences. January 2013;2(1):1-9.
16. Jayesh D B, Sharad K, Yogesh C, Seth A, Gajanan J, Deshmukh, et al. Development of the spectrophotometric method for the simultaneous estimation of Piogliazone and Metformin. Int J of pharmaceutical sciences. july 2011;2(3):236-43.
17. Lalit K, Navpreet K. Estimation of Pioglitazone and Glimipride in its pharmaceutical dosage form by spectrophotometric methods.Scholars Research Library ,Der Pharmacia Lettre. 2011;3(4):276-84.
18. Freddy H H, Dharmendra L V. Simultaneous estimation of Metformin hydrochloride, Rosiglitazone and Pioglitazone hydrochloride in the tablets dosage form. Int J of Applied Biology and Pharmaceutical Technology. nov-dec 2010;1(3):1000-5.
19. Sireesha.M, Chandan R S, Gurupadayya S M, Aswani Kumar C H. Selective and validated spectrophotometric methods for determination of Rosiglitazone and Pioglitazone with 2, 4-dnp. Int J of Biological and Lifesciences.2006;2(1):52-8.
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