FORMULATION AND EVALUATION OF DISPERSIBLE TABLETS CONTAINING THIRD GENERATION CEPHALOSPORINS
SYNOPSIS FOR
M.PHARM DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA.
SUBMITTED BY
SWAPNA VELLANKI
M.PHARM PART 1st YEAR
DEPARTMENT OF PHARMACEUTICS
UNDER THE GUIDANCE OF
Mrs. SURINDER KAUR
Assistant Professor
THE OXFORD COLLEGE OF PHARMACY,
BENGALURU
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA.
ANNEXURE – II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1. / Name of the candidate and address / Mrs. SWAPNA.VELLANKIDEPARTMENT OF PHARMACEUTICS,
THE OXFORD COLLEGE OF PHARMACY,
No.6/9, 1ST CROSS, BEGUR ROAD,
HONGASANDRA, BENGALURU –560 068
KARNATAKA.
PERMANENT ADDRESS
D-603, SALARPURIA SERENITY,
5th MAIN, 7th SECTOR,
HSR LAYOUT
BENGALURU,
KARNATAKA-560102.
2. / Name of the institution / THE OXFORD COLLEGE OF PHARMACY,
No.6/9, 1ST CROSS, BEGUR ROAD,
HONGASANDRA, BENGALURU –560 068
KARNATAKA.
3. / Course of study and subject / Master of Pharmacy in Pharmaceutics
4. / Date of admission to course / 22/10/ 2010
5. / Title of the topic:
“FORMULATION AND EVALUATION OF DISPERSIBLE TABLETS CONTAINING THIRD GENERATION CEPHALOSPORINS”
6.
7.
8. / Brief Resume of Intended Work:
6.1: Need for the Study:
Ø Third generation cephalosporin antibiotic is indicated for the treatment of upper respiratory tract infections including acute otitis media, sinusitis, tonsillitis and pharyngitis. Acute uncomplicated gonnorrhea, uncomplicated urinary tract infections and skin structure infections1.
Ø Drug acts by inhibiting the final stages in the synthesis of peptidoglycan in the bacterial cell wall, resulting in loss of mechanical strength of the bacterial cell wall. The final stage in the synthesis of peptidoglycans involves cross-linking where by the terminal glycine residue of the Pentaglycine Bridge is linked to the fourth residue of the pentapeptide (D-alanine). Cephalosporins inhibit the transpeptidase enzyme that is responsible for completing the process. The end result is the bacterial cell wall is weakened cell swells and ruptures2.
Ø The adjustment of adult formulation to paediatrics dosage and difficulty in pill swallowing affects significant population of the people, mainly affects geriatrics and paediatrics.
Ø To avoid this problem dispersible tablets have been developed.
Ø Dispersible tablets are uncoated or film-coated tablets intended to be dispersed in water before administration giving a homogeneous dispersion3.
Ø Dispersible tablets are easy to swallow, disintegrate rapidly in water so they are particularly suitable for geriatric patients with swallowing difficulties and for paediatrics.
Ø Typically a dispersible tablet is dispersed in about 5-15 ml of water and the resulting dispersion is administered to the patient.
Ø Dispersible tablets are required to disintegrate within 3 minutes in water4.
Ø They have quicker onset of action and improved patient compliance5.
Ø The bitter taste of active substance must be masked in advance.
Ø Many medicines are only available in adult strength, therefore the administration of accurate dosage for children is critical. The taste of the medications is also an important parameter to adherence, treatment and compliance6.
Ø The bioavailability of drugs from quick dispersing oral drug delivery system may be greater compared to the conventional oral dosage forms7.
6.2: Review of literature
1. A polymer carrier system was developed and it was reported to reduce the bitterness of erythromycin and its derivative clarithromycin by adsorption to carrier carbomer 934 (Carbopol 934). A series of in-vitro equilibrium studies, taste screening, and bioavailability studies in dogs established the characteristics for various drug-polymer ratios. Taste protection was further improved by encapsulating the adsorbate particles with polymer coatings. Hydroxypropyl methylcellulose phthalate provided the best combination of suspension stability, taste protection, and bioavailability8.
2. Rapidly disintegrating and readily suspendible tablets consists of the active ingredient, croscarmellose sodium, microcrystalline cellulose and a co-processed additive consisting of microcrystalline cellulose, calcium and sodium alginate complex was formulated. It was reported that these tablets were suitable for oral administration of measured-dose suspensions of either water- soluble or water insoluble pharmaceuticals9.
3. Formulation of compressed tablets intended for rapid disintegration in saliva and designed to mask the bitter taste of model drugs pirenzepine hydrochloride and oxybutynin chloride. The materials used include granules containing these model drugs, Eudragit E-100, cellulose microcrystalline, hydroxypropyl cellulose, and magnesium stearate. The disintegration and dissolution of the tablets in-vitro and the disintegration and masking of the bitter taste of the tablets in-vivo were studied and it was reported that, tablets disintegrated within 20 seconds in the saliva of the volunteers and they did not report a bitter taste after disintegration10.
4. A work on Orodispersible tablets containing Fexofenadine wsa done and it was reported to disintegrate in the buccal cavity upon contact with saliva. Drug is present as coated granules, and the excipients include disintegrating agent, soluble diluent, lubricant, and optionally a swelling agent, sweeteners, flavouring agents and colours11.
5. To mask the unpleasant taste of diclofenac sodium, four different techniques were employed: wet granulation using ethyl cellulose as a binder of a mixture of diclofenac sodium/microcrystalline cellulose and/ or mannitol; ethyl cellulose pan coating of diclofenac sodium or its mixture with mannitol;microencapsulation using ethyl cellulose as wall forming material and inclusion complexation with beta-cyclodextrin. The treated diclofenac sodium was evaluated with regard to taste, particle size, flowability, dissolution and drug content12.
6. A water-dispersible tablet comprising of an active compound such as Acyclovir or Lamotrigine and dispersing agents such as smectite, veegum or bentonite was done. It was reported to be dispersing in water within 3 minutes to provide a dispersion which will pass through a 710 µm sieve. The tablet can optionally be film coated in which case the dispersion time is less than 5 minutes13.
7. A composition were prepared for rapid disintegrating tablet in oral cavity and it having a shortened disintegration time in oral cavity as well as a sufficient hardness with compared to rapid disintegrating tablets of the prior art. The tablet comprises of mannitol, xylitol, an inorganic excipient and a disintegrating agent, where in mannitol and xylitol form complex particles and the inorganic excipient and the disintegrating agent are dispersed in the complex particles. The disintegrating agents used were croscarmellose sodium, crospovidone, low-substituted hydroxyl propyl cellulose, and/ or crystalline cellulose14.
8. Various formulations were developed to achieve fast dissolution/dispersion of tablets in the oral cavity. In particular, this review describes in detail FDT technologies based on lyophilization, molding, sublimation, and compaction, as well as approaches to enhance the FDT properties, such as spray-drying, moisture
treatment, sintering, and use of sugar-based disintegrants. In addition, taste masking technologies, experimental measurements of disintegration times, and clinical studies are also discussed15.
9. The rapidly disintegrating tablets intended to be used as orodispersible tablets or dispersible tablets were studied using silicified microcrystalline cellulose.It was reported that it is suitable for use in paediatric patients in the age above 3 years and specially for antibiotics .They are ingested either by dispersing directly in the mouth or in water. For paediatric patients under 3 years the same tablets can be used as dispersible tablets16.
10. A work was done on dispersible tablet comprising of beta-lactam antibiotics for oral administration. The formulation consisted of intra and extra granular disintegrants like croscarmellose sodium or sodium starch glycolate; filler like lactose or microcrystalline cellulose and lubricants like talc, colloidal silicon dioxide or magnesium stearate. It was reported that, these tablets showed a disintegration time of less than 1 minute. The tablets formed a suspension after incorporating into aqueous media and the formed suspension completely passes through a 750 µm sieve17.
6.3 Objective of the study:
In the present work attempt will be made:
· To carry out Preformulation studies.
· To prepare dispersible tablets containing antibiotic drug.
· To mask the bitter taste of the drug.
· To carry out in-vitro dissolution studies of formulated tablets and to improve the dissolution rate of drug product.
· To study the effect of various super disintegrants in the dispersion time of tablets.
Preparation of dispersible tablets:
The dispersible tablets can be prepared by any of the following methods:
a. Dry granulation method
b. Direct compression method
Evaluation of tablets:
· Evaluation of the formulation consists of:
ü Thickness
ü Weight variation
ü Hardness and friability
ü Disintegration test
ü Uniformity of dispersion.
7.0 Materials and Methods
Drug: The drug of choice for the project is selected from the category third generation cephalosporin broad spectrum antibiotic. The drug can be cefpodoxime, cefetamet, cefcapene, cefixime, cefdaloxime etc.
Excipient: It will be chosen after studying the compatibility with the active ingredient.
Method: Dry Granulation, Direct Compression.
7.1 Source of data:
Ø Data was obtained from Drug invention today, Pubmed, Science direct, Medline, US patent office website & other Internet facilities, various books, literature search and Related Articles from library of The Oxford college of Pharmacy.
7.2 Method of collection of data:
The data will be collected from the prepared formulation on the basis
Ø Formulation of reproducible batches of the preparation.
Ø Evaluation of the formulation consists of:
ü Thickness
ü Weight variation
ü Hardness and friability
ü Disintegration test
ü Uniformity of dispersion18.
7.3 Does the study require any investigations or interventions to be
Conducted on patients or other humans or animals? If so, please
Describe in brief.
Not applicable
7.4 Has ethical clearance been obtained from your institute in case 7.3?
Not applicable
References:
1. Richard F, Michelle AC, Luigi X. Lippincott's illustrated reviews Pharmacology. 4th ed. 2009. p.611-12.
2. Laurence LB, Keith LP, Donald KB, Iain LOB. Goodman & Gilman's The Pharmacological Basis Of Therapeutics. 11th ed. 2006. p. 1206.
3. European Pharmacopoeia 2005 Jan; 5:628.
4. Anhui New Star Pharmaceutical Development Co.,Ltd. Cefaclor Dispersible Tablets http://www.newstarchem.com/english/display.asp?id=209
5. Mepha, The Innovative swiss Pharmaceutical Company. Dispersible tablets. In: Mepha.com2008 March 31 Available at: http://www.mepha.com/about/rd/Pages/Dispersibletablets.aspx
6. Unicef. Dispersible Tablets.In:Unicef.org. 2010 March 12th
Avaialble from: http://www.unicef.org/supply/index_53571.html
7. Amin, P, Prabhu N, Wadhwani A. Indion 414 as superdisintegrant in formulation of mouth dissolve tablets. Indian J. of Pharmaceutical Sciences [Online] 2006; 117-9.
8. Lu MF, Borodkin S, Woodward L, Li P, Vadnere M. Polymer carrier system for taste masking of Macrolide antibiotics. Pharmaceutical Research 1991Jun; 8:706-12.
9. Augello, Dell, Agyilirah, Reier. Pharmaceutical suspension tablet compositions. United States Patent 5955107; 1999 Sep 21.
10. Ishikawa T, Watanabe Y, Utoguchi N, Matsumoto M. Preparation and evaluation of tablets rapidly disintegrating in saliva containing bitter taste masked granules by the compression method. Chemical and Pharmaceutical Bullettin 1999 Oct; 47:1451-4.
11. Faham, Amina, Marechal, Dominique, Chenevier, Philippe. Orodispersible tablets containing Fexofenadine. United States Patent 20030099700; 2003 May 29.
12. Al Omran MF, Al Suwayesh SA, El Helw AM, Saleh SI. Taste masking of diclofenac sodium employing four different techniques. Saudi Pharm. J. 2002; 10(3): 106-13.
13. Fielden, Elzbieta k. Water-dispersible tablets. United States Patent 5698226; 1997 Dec 16.
14. Tanaka, Nagai, Kawaguchi, Fukami, Hosokawa. Composition for rapid disintegrating tablet in oral cavity. United States Patent 20050106240; 2005 May 19.
15. Fu YR, Yang SC, Jeong SH, Kimura S, Park K. Orally fast disintegrating tablets: Developments, technologies, taste-masking and clinical studies. Crit. Rev in Therapeutic Drug Carrier Systems 2004; 21(6): 433-475. J. Pharm Sci and Tech. 2005; 65(1):55-9.
16. Skulj, Vesna, Sirca, Judita, Jenko Osel. Rapidly disintegrating tablet. United States Patent 20060115528; 2006 Jun 01.
17. Isloor, Bhand, Bhushan, Malik. Dispersible tablet for oral administration. United States Patent 20060110445; 2006 May 25.
18. Indian Pharmacopoeia 2007; 2:662-4.
9. / Signature of the Candidate: / (SWAPNA VELLANKI)
10. / Remarks of the Guide: The above information is true to the best of my knowledge and the work will be done under my guidance.
11. / Name & Designation
11.1 Guide: / Mrs. SURINDER KAUR
11.2 Signature:
11.3 Co-guide: / Mr. BALAJI.G
EXCEUTIVE OFFICER
RESEARCH AND DEVELOPMENT
GELTEC PVT. LTD, YEDAVANAHALLI, BENGALURU.
11.4 Signature:
11.5 Head of the Department / Dr. KALAYANI PRAKASAM
11.6 Signature of HOD:
12. / 12.1 Remarks of the Principal: The above mentioned information is correct and I recommend the same for approval. R
12.2 Signature of the Principal / (Dr. PADMAA M PAARAKH)