Comparative Study on Effect of Different Techniques Used in Development of Candesartan

COMPARATIVE STUDY ON EFFECTOF DIFFERENT TECHNIQUES USED IN DEVELOPMENT OF CANDESARTAN CILEXETIL

FAST DISSOLVING TABLETS

M.PHARM. DISSERTATION PROTOCOL

Submitted to

RajivGandhiUniversity of Health Sciences

Bangalore, Karnataka.

By

Mr.Gada Mahesh MahadeoB.Pharm.

Under the Guidance

of

Prof.Basawaraj S. PatilM.Pharm. (Ph.D.)

DEPARTMENT OF PHARMACEUTICS

R.M.E.S’s COLLEGE OF PHARMACY

GULBARGA-585102

2009-2010

RajivGandhiUniversity of Health Sciences

Bangalore, Karnataka

Curriculum Development Cell

Conformation for Registration of

Subject for Dissertation

Registration No.:

Name of the Candidate:GADA MAHESH MAHADEO

Address:R.M.E.S’s College of Pharmacy

Gulbarga, Karnataka. 585102

Name of the Institution:R.M.E.S’s College of Pharmacy

Gulbarga, Karnataka.

Course of Study and Subject :M.Pharm. in Pharmaceutics

Date of Admission to the Course:24thOct. 2009

Title of the Topic :Comparative study on effect of different techniques

used in development of Candesartan Cilexetil fast dissolving tablets

Brief resume of the intended work:Enclosed

Signature of the student:

Guide Name: Prof.Basawaraj S. Patil.M.Pharm.(Ph.D.)

Remarks of the Guide :Recommended for approval.

Signature of the Guide:

Co-Guide Name:Mr. Upendra Kulkarni.M.Pharm.(Ph.D.)

Signature of the Co-Guide:

HOD Name:Prof. Hariprasanna R.ChitapurkarM.Pharm.(Ph.D.)

Signature of the HOD:

Director/Principal Name: Prof. Kishoresingh K.ChatrapathiM.Pharm. Ph.D.

Mobile No:+919880200905.

Director/Principal E-mail ID:

Remarks of Director/ principal: Recommended for approval.

Director/Principal Signature:

RajivGandhiUniversity of Health Sciences,Karnataka,Bangalore.

ANNEXURE - II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. / Name and Address of the candidate / GADA MAHESH MAHADEO.
13, East Mangalwar Peth, Govind Complex,
Flat No.2 Solapur- 413002, Maharashtra.
2. / Name of the Institution / R.M.E.S’s College of Pharmacy,
Gulbarga– 585102, Karnataka.
3. / Course of study and subject / Master of Pharmacy in Pharmaceutics.
4. / Date of admission to course / 24th Oct 2009.
5. / Title of the topic / Comparative study on effect of different techniques used in development of
Candesartan Cilexetil fast dissolving tablets.
6. / Brief resume of the intended work
6.1 Need of the study
Now a day fast dissolving tablets are gaining more importance in the market. Currently these tablets are available in the market for treating many disease conditions. More is concerned on hypertension, migraine, dysphasia, nausea and vomiting, Parkinson’s disease, schizophrenia, pediatric emergency1-7. These conditions are those which require the drug to be formulated as fast dissolving tablets. Some patient prefers fast dissolving tablets to conventional tabletsbest of ease of administration, swallowing, pleasant taste and availability in several flavors8.
The paediatric and geriatric patients are of particular concern. To overcome this, dispersible tablets9 and fast-disintegrating tablets10 have been developed. Most commonly used methods to prepare these tablets are; freeze-drying/lyophilization11 tablet molding12 and direct-compression methods13. Lyophilized tablets show a very porous structure, which causes quick penetration of saliva in to the pores when placed in oral cavity14. The main disadvantages of tablets produced are, in addition to the cost intensive production process, a lack of physical resistance in standard blister packs and their limited ability to incorporate higher concentrations of active drug. Molded tablets dissolve completely and rapidly. However, lack of strength and taste masking are of great concern15. Main advantages of direct compression are low manufacturing cost and high mechanical integrity of the tablets16.
The rate of dissolution can be increased by increasing the surface area of available drug by various methods (micronization, complexation and solid dispersion)17. The dissolution of drug can also be influenced by disintegration time of the tablet. Faster disintegration of tablets delivers a fine suspension of drug particles resulting in a higher surface area and faster dissolution18.
Candesartan Cilexetil is an angiotensin II receptor antagonist used mainly for treatment of hypertension. The half life drug is 5.1-10.5 hours with poor bioavailability (15%)19.
Hence, in the present research work fast dissolving tablets of Candesartan Cilexetil will be prepared by using different techniques. Effect of various methods on dissolution rate, disintegration time and wetting time will be studied.
6.2 Review of Literature
1)Raghavendra Rao N. G. et al.20. Formulated Chlorthalidone fast dissolving tablets by using superdisintegrant, co-grinding with carriers (PVP and mannitol), solid dispersion with same and by sublimation method. The results revealed that tablets prepared by sublimation method using 40% camphor significantly enhanced the dissolution rate of drug. Tablets prepared by co-grinding with PVP without crospovidone gave inferior dissolution rates. Tablets containing solid dispersion with crospovidone yielded good results in terms of dissolution rate.
2)Shu. et al.21.Formulated rapid oral disintegration tablets by direct compression using co-ground mixture of D-mannitol and crospovidone. The tablets manufacturing from a physical mixture of 30% (w/v) co-ground mixture of D-mannitol and crospovidone (mixed ratio 9:1) with 65.5% (w/v) of non-ground mannitol, 4% (w/v) of Crospovidone, and 0.5% (w/v) of magnesium stearate had good properties for rapidly disintegrating tablets in the oral cavity. The presumed that Crospovidone acted as a grinding assistant for D-mannitol in the co-grinding process, enhancing the hardness of tablets by increasing the contact area among powder particles.
3)Raghavendra Rao N. G. et al.22. Formulated Carbamazepine fast dissolving tablet by solid dispersion technique using different concentrations of croscarmellose sodium as superdisintegrating agent and study the effect of various carrier on solid disoperation techniques. The formulation prepared with mannitol solid dispersion were showed disintegration time between the range of 11.83-17.79 sec and drug release showed between the ranges of 8-10 min. however the formulations prepared with PEG-6000 and PVP solid dispersion did not disintegrate in specified limit of time for fast dissolving tablets.
4)Narmada G. Y. et al.23.Formulated fast dissolving tablet of Amlodipine Basylate. All formulations were evaluated for pre-compression and post-compression parameters, wetting time and water absorption ratio. The results obtained showed that the quantity of starch potato, sodium starch glycolate, camphor significantly affect response variables. The results indicate that the optimized tablet formulation provides a short DT of 8 seconds with sufficient crushing strength and acceptable friability. Stability studies of optimized formulation revealed that formulation is stable.
5)S.B. Shirsand et al.24. Degned. Fast dissolving tablets by Novel co-processed superdisintegrants were developed by solvent evaporation method using crospovidone and sodium starch glycolate in different ratios (1:1, 1:2 and 1:3). Among the designed formulations, the formulation CP1 containing 4%w/w of co-processed superdisintegrant emerged as the oral best formulation.
6)Lalla et al.25. Prepared inclusion complex of Rofecoxib, an NSAID with β-cyclodextrin using ball milling technique and evaluated using DSC. Fast dissolving tablets composition with 25 mg equivalent Rofecoxib showed complete release of Rofecoxib in 12 minutes as compared to 20% drug released form the conventional release marketed tablets during the same period of time.
7)C. Mallikarjuna Setty. et al.26. Developed fast dispersible Aceclofenac tablets by direct compression method. Effect of superdisintegrants (such as, croscarmellose sodium, sodium starch glycolate and crospovidone) on wetting time, disintegration time, drug content, in-vitro release and stability parameters has been studied. Disintegration time and dissolution parameters (t50% and t80%) decreased with increasing the level of croscarmellose sodium. Where as, disintegration time and dissolution parameters increased with increase in level of sodium starch glycolate in tablets. However, the disintegration time values did not reflect in the dissolution parameter values of crospovidone tablets and release was dependent on the aggregate size in the dissolution medium. Stability studies indicated that tablets containing superdisintegrants were sensitive to high humidity conditions. It is concluded that fast-dispersible Aceclofenac tablets could be prepared by direct compression using superdisintegrants.
8)Deshmukh Sambhaji S., et al.27. Formulated formulation of Ziprasidone Hydrochloride fast dissolving tablet. For enhancing solubility of drug, inclusion complexes of drug were prepared using βCD and HPβCD. To aid in faster disintegration of tablets, superdisintegrants in different proportions were used and their effect on disintegration was studied. The inclusion complexes with HPβCD prepared by microwave method exhibited highest enhancement in solubility (0.024 gm /100ml) and also showed faster dissolution profile (100% drug release in 5 min.). So this complex was worked further for formulation of Ziprasidone Hydrochloride faster disintegrating/dissolving tablets. Among the tablet formulations prepared using different superdisintegrants, those with 5%w/w polyplasodone showed the lowest disintegration time (21sec) and fastest dissolution profile.
9)Rahul K. et al.28. Formulated fast dissolving tablets of Tizanidine Hydrochloride by direct compression method using Sodium Starch Glycolate, Ac-Da-Sol and Indion 414 as super disintegrats and controlled tablets without any super disintegrants and evaluated for hardness, friability, disintegration time, dissolution time, water absorption ratio and content uniformity. All tablets containing superdisintegrants shows release of drug more than 95% within 10 minutes and controlled tablets shows release of drug after 30 minutes. Tablets containing Indion 414 as a superdisintegrant shows better results compare to others. Result also shows that as the concentration of superdisintegrant increases percentage release also increases.
10)Mahaparale. et al.28. Prepared solid dispersion of Meloxicam by solvent evaporation method with polyvinyl pyrrolidone (PVP), polyethylene glycol 6000 (PEG 6000) and polyethylene glycol 4000 (PEG 4000) dissolution study was carried out for all solid dispersion. All solid dispersion of Meloxicam showed higher solubility and faster dissolution than pure drug alone. Meloxicam : PVP (1:9) ratio showed highest solubility and faster dissolution than any other solid dispersion.
11)Desai. et al.29.Prepared orodissolving tablets of Promethazine Hydrochloride using superdisintegrants, sodium starch glycolate and croscarmellose sodium by direct compression method. The formulations containing 4% of sodium starch glycolate and 1-3% of croscarmellose sodium were found to give the best results. Thus, the tablets apart from fulfilling all official and other specifications, exhibited higher rate of release.
12)D.M. Patel. et al.30. Optimized fast dissolving Etoricoxib tablets prepared by sublimation technique. Granules containing Etoricoxib, menthol, crospovidone, aspartame and mannitol were prepared by wet granulation technique. Menthol was sublimed from the granules by exposing granules to vacuum. The tablets were evaluated for percentage friability and disintegration time. Sublimation of menthol from tablets resulted in rapid disintegration as compare with the tablets prepared from granules that were exposed to vacuum. The optimized tablet formulation was compared with conventional marketed tablets for percentage drug dissolved in 30 minutes (Q30) and dissolution efficiency after 30 minute (DE30). From the results, it was concluded that fast dissolving tablets with improved Etoricoxib dissolution could be prepared by sublimation of tablets containing suitable subliming agent.
13)Srinivas Babu. et al.31. Prepared solid dispersion of Piroxicam in five super disintegrants namely primogel, microcrystalline cellulose, crospovidone, pregeletinized starch, croscarmellose sodium and with water soluble carriers polyvinyl pyrrolidone and polyethylene glycol. Solid dispersions of Piroxicam in super disintegrants gave a marked enhancement in its dissolution rate and dissolution efficiency. Solid dispersion in super disintegrants could be used as an effective and efficient technique for enhancing the dissolution rate of Piroxicam a poorly soluble drug.
14)Chowdary K.P.R et al.32. Prepared solid dispersion of Itraconazole in lactose, microcrystalline cellulose and three superdisintegrants (Primogel, Kollidon CL, and Ac-Di-Sol) and their formulations into tablets were investigated with an objective of enhancing the dissolution rate of Itraconazole from tablet formulations. A marked enhancement in the order of the excipients to enhance the dissolution rate was Ac-Di-Sol.
6.3Objectives of the study
The present research investigation is planned with the following objectives.
1)To formulate fast dissolving tablets of Candesartan Cilexetil by different techniques.
2)To compare the effect of different techniques used to prepare fast dissolving tablets on disintegration time, wetting time, water absorption ratio and percent drug release.
3)To evaluate the formulations with respect to various physical parameters.
4)To evaluate the formulations with respect to content uniformity, in vitro release studies, etc.
5)To characterize the formulation by instrumental methods like FTIR, DSC and XRD studies.
6)To perform the stability studies on promised formulations.
7. / Material and Methods:
7.1Source of data:
Primary data: This data will be collected by conducting laboratory experiment and recording the observation.
Secondary data: This will be collected from various journals and text book
7.2 Method of Collection of Data:
The data for the study is planned to collect from the laboratories based on experiment which include the following:
-Formulation and development of fast dissolving tablets containing Candesartan Cilexetil.
-Evaluation fast dissolving tablets with respect to drug content determination and in- vitrorelease study.
-Evaluation of fast dissolving tablets with respect to some physical parameter
7.3Does the study require any investigation to be conducted on patients, other humans or animals? If so, please describe briefly.
Not under the plan of work.
7.4 Has ethical clearance been obtained from your institution in case of 7.3
Not applicable
8. / List of References:
1)Shiwaikar AA, Ramesh A Ind. J. Pharm. Sci. 2004;66(4):422-6
2)Diener HC, Gendolla A. Part IV: Curr Med Res Opin 2005;21 (3):S18-24.
3)Carnaby Mann G, Crary M. Pill swallowing by adults with dysphagia. Arch Otolaryngol Head Neck Surg 2005 Nov; 131(11):970-5.
4)Hartsell T, Long D, Kirchs JR. Anesth Analg 2005 Nov; 101(5): 1492-6.
5)Lew MF. Expert Rev Neurother 2005 Nov; 5(6): 705-12.
6)Chue P, Welch R, Binder C. Can J Psychiatry 2004 Oct; 49(10):701-3.
7)Freedman SB, Adler M, Shesadri R, Powell EC. Engl J Med 2006 Apr 20;354(16): 1698-705.
8)Popa G, Gafitanu E. Rev Med Chir Soc Med Nat lasi 2003 Apr; 107(2): 337-42.
9)Scheirmeier S, Schmidt PC. Eur J Pharm Sci 2002; 15:295-305.
10)Mizumoto T, Masuda Y, Yamamoto T, Yonemochi E, Tarada K. Int J Pharm 2005; 306:83-90.
11)Virley P,Yarwood R. Zydis. Manuf Chem 1990;61:22-9.
12)Dobetti L. Pharm Technol Eur 2000; 12:32-42.
13)Bi Y, Sunada H, Yonezawa Y, Danjo K, Otsuka A, lida K.Chem Pharm Bull 1996;44:2121-7.
14)Patrick K, Sang KW. US Patent 5 631 023; 1997.
15)Chang RK, Guo X, Burnside B, Couch R. Pharm Technol 2000; 24:52-8.
16)Takao M, Yoshinori M, Muneo F. US patent 5 576 014; 1996.
17)Martin A, editor. Physical pharmacy. 4th edition. Philadelphia: Lippincott Williams and Wilkins; 1993. p. 324-62.
18)Alfred Martin. Physical pharmacy. 4th edition. Philadelphia: Lippincott Williams and Wilkins; 1993.
19)http;//en.wikipedia.org/wiki/candesartan. 28th apr. 2010.
20)Raghavendra Rao NG, Ravi Kumar, Upendra Kulkarni. Comparative study on effect of different techniques use in development of Chorthalidone fast dissolving tablets. RJPBCS Volume1 Issue2. p-172-186.
21)Shu T, Suzuki H, Hirokana K, Ito K. Studies of rapidly disintegrating tablets in the oral cavity using co-ground mixtures of mannitol with crospovidone. Chem Pharm Bull 2002; 50(2):193-8.
22)N.G. Raghavendra Rao, Upendra Kulkarni. Development of Carbamazepine fast dissolving tablets: Effect of functionality of hydrophilic carriers on solid dispersion technique. Asian Jr. Ph and Cli. Res.Vol.3. Issue 2, April-June 2010.
23)Narmada GY, Mohini K, Prakash Rao B, Gowrinath DXP, KumarKS. Formulation, evaluation and optimization of fast dissolving tablets containing Amlodipine Besylate by Sublimation method. Ars pharma, 2009, Vol 50 no 3;129-144.
24)S.B.Shirsand, R.G. Ramani, P.V.Swamy. Novel co-processed superdisintegranta in the design of fast dissolving tablets. Int. j. Pharm. Bio. Sci. V1(1)2010. p. 1-12.
25)Lalla JK, Mamania HM. Fast dissolving Rofecoxib tablets. Indian J Pharm Sci 2004 May; 66(4): 350-3.
26)C. Mallikarjuna Shetty, D.V.K. Prasad, V.R.M Gupta and B. SA. Development of fast dispersible Aceclofenac tablets: Effect of functionality of super disintegrants. Ind. J. Pharm. Sci March- April 2008. p. 180-185.
27)Rahul K. Godge, Prakash N. Kendre, Mahendra A. Giri, Syed M. Zama, Syed N. Lateel. Formulation and In-vitro Evaluation of Fast Dissolving / Disintegrating Tablets of Tizanidine Hydrochloride. Res. J. Pharm. Dosage forms and Tech. 2009; 1(1): 55-58.
28) Mahaparale P R, Gudsoorkar VR, Gajeli GB, Kuchekar BS. Studies on solid dispersion of Meloxicam. Indian J Pharm Sci 2006; 40(3) 172-4.
29) Desai SA, Khavade SV, Petkar KC, Kuchekar BS. Orodissolving tablets of Promethazine Hydrochloride. Indian J Pharm Sci 2006; 40(3) 172-4.
30)D. M. Patel and M. M Patel. Optimization of Fast Dissolving Etoricoxib Tablets Prepared by Sublimation Technique. Ind. J. Pharm. Sci. January – February 2008. 71-76.
31) Srinivas Babu P, Ramu A, Sasidhar R, Vidhyadhara. Enhancement of dissolution rate of Piroxicam by solid dispersion using newer carriers. The Pharma review 2007; 163-6.
32)Chowdary K.P.R., Rao SS. Investigation of Dissolution enhancement of Itraconazole by solid dispersion in superdisintegrants. Drug DevInd Pharm 2000 Nov; 26(11) 1207-11.
9. / Signature of the Candidate
10. / Remark of the Guide / The present work is aimed to increase the solubility of drug, bioavailability and patient compliance.
So, recommended for registration.
11. / 11.1 Name & Designation of the Guide / Prof. Basawaraj S. Patil M.Pharm.(Ph.D.)
Department of Pharmaceutics,
R.M.E.S.’s College of Pharmacy,
Gulbarga-585102.
11.2 Signature
11.3 Co-Guide (if any) / Mr. Upendra Kulkarni, M.Pharm.(Ph.D.)
Lecturer,
Department of Pharmaceutics
R.M.E.S.’s College of Pharmacy,
Gulbarga-585102.
11.4 Signature
11.5 Head of the department / Prof. Hariprasanna R. C. M.Pharm.(Ph.D.)
Professor & HOD
Department of Pharmaceutics
R.M.E.S.’s College of Pharmacy, Gulbarga.
11.6 Signature
12. / 12.1 Remark of the Director /
Principal / We will provide all the necessary facility for the proposed research work.
So, recommended for registration.
12.2 Signature / Prof. Kishoresingh K.C. M.Pharm. Ph.D.
Director/Principal
R.M.E.S.’s College of Pharmacy, Gulbarga.