Formulation and In-Vitro Evaluation Of

FORMULATION AND IN-VITRO EVALUATION OF

MUCOADHESIVE BUCCAL TABLET OF GLICLAZIDE

Synopsis for M. Pharm Dissertation submitted to the

Rajiv Gandhi University of Health Sciences Karnataka, Bangalore.

By

Ms.KRUPASHOURSEE K G

M. Pharm., Part-I

Under the guidance of

Mr. S. PARTHIBAN., M. Pharm.,

DEPARTMENT OF PHARMACEUTICS,

BHARATHI COLLEGE OF PHARMACY,

BHARATHINAGARA.

2013-2014

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / NAME OF THE CANDIDATE
AND ADDRESS / KRUPASHOURSEE K G M.PHARM., PART-I,
DEPARTMENT OF PHARMACEUTICS,
BHARATHI COLLEGE OF PHARMACY,
BHARATHI NAGARA, MANDYA,
KARNATAKA-571422.
2. /

NAME OF THE INSTITUTION

/ BHARATHI COLLEGE OF PHARMACY,
BHARATHI NAGARA.
3. /

COURSE OF STUDY AND SUBJECT

/ MASTER OF PHARMACY IN PHARMACEUTICS.
4. / DATE OF ADMISSION OF COURSE / 05/08/2013
5. / TITLE OF TOPIC / FORMULATION AND IN-VITRO EVALUATION OF MUCOADHESIVE BUCCAL TABLET OF GLICLAZIDE.
6. / BRIEF RESUME OF THE INTENDED WORK
6.1 Need for the study
6.2 Review of the literature
6.3 Objectives of the study /
ENCLOSURE - I
ENCLOSURE - II
ENCLOSURE – III
7. /

MATERIALS AND METHODS

7.1 Source of data

7.2 Method of collection of data

7.3Does study requires any investigation or interventions to be conducted on patients or other human or animal? If so, please describe briefly.

7.4 Has ethical clearance been obtained from your institution in case of 7.3

/ ENCLOSURE - IV
ENCLOSURE - V
ENCLOSURE - VI
ENCLOSURE – VI
8. / LIST OF REFERENCES / ENCLOSURE – VII
6.0
7.0
8.0 / Brief resume of the intended work:
ENCLOSURE – I
6.1 – NEED FOR THE STUDY:
In recent years, there has been a growing interest in the use of delivery of therapeutic agent thoursough various transmucosal routes to provide a therapeutic amount of drug to the proper site in body to promptly achieve and then maintain the desired concentration. The unique environment of the oral cavity offers its potential as a site for drug delivery. Because of the rich blood supply, higher bioavailability, lymphatic drainage and direct access to systemic circulation, the oral mucosal route is suitable for drugs which are susceptible to acid hydrolysis in the stomach or which are extensively metabolized in the liver. The thin mucin film, which exists on the surface of the oral mucosa, may provide an opportunity to retain a drug delivery system in contact with the mucosa for prolonged period, if it is designed to be mucoadhesive. Such system ensures close contact with absorbing membrane, thus optimizing the drug concentration gradient across the biological membrane and reducing the differential pathway. Therefore, the oral mucosa may be potential site for controlled or sustained drug delivery.1
The buccal region of the oral cavity is an attractive target for administration of the drug of choice. Moreover buccal drug absorption can be promptly terminated in case of toxicity by removing the dosage form from the buccal cavity therefore mucoadhesive dosage forms were suggested for oral drug delivary. 2
Gliclazide is a second generation sulfonyl urea used in the treatment of diabetes. Gliclazide is selected as model drug for investigation because of its suitable properties like low dose (5 mg), half life of 10.4 hourss and molecular weight (323.412 g/mol). Prior research work revealed that it has good general tolerability, low incidence of hypoglycemia and low rate of secondary failure. In addition; it has the potential for slowing the progression of diabetic retinopathy. For these reasons, it appears to be a drug of choice in prolonged therapy for the control of NIDDM. However, the drawback of this potentially useful hypoglycemic agent is that it belongs to BCS class 2 and therefore is highly hydrophobic and practically insoluble in water.
In general, rapid gastrointestinal (GI) absorption is required for oral hypoglycemic drugs, in order to prevent a sudden increase in blood glucose level after food intake in patients with diabetes mellitus. However, the GI absorption rate of Gliclazide in conventional dosage form appears to be rather slow. Several studies using healthy volunteers or patients revealed that the time to reach peak serum concentration ranged from 2 to 8 hours following oral administration of a conventional tablet. Slow absorption of a drug usually originates from either its poor dissolution from the formulation or poor permeability across the GI membrane. This eventually limits its oral bioavailability and therapeutic efficacy.3
Hence, this the present study we plan to formulate buccal tablets to increase its permeability and bioavailability.
ENCLOSURE-II
6.2 REVIEW OF LITERATURE
·  Han-Gon Choi et al., developed Omeprazole buccal adhesive tablets composed of sodium alginate, hydroxypropylmethylcellulose (HPMC), magnesium oxide and croscarmellose sodium. They reported that the tablets may be attached to the human cheek without collapse and it enhanced the stability of Omeprazole in human saliva for at least 4 hours, giving a fast release of Omeprazole.4
·  Harikrishna Boyapally et al., developed Theophylline buccal adhesive tablets using direct compression using a water soluble resin with various combinations of mucoadhesive polymers. They assessed ex-vivo mucoadhesion using porcine gingival tissue and the peak detachment forces were found to be suitable for a buccal adhesive tablet with a maximum of 1.5N approximately. The effect of formulation composition on the release pattern was also investigated which showed Theophylline controlled release profiles depended on the grade and polymer ratio.5
·  Paolo Giunchedi et al., Investigated buccal formulations (tablets) based on chitosan microspheres containing Chlorhexidine diacetate prepared by a spray-drying technique. The loading of chlorhexidine into chitosan is able to maintain or improve the anti-microbial activity of the drug. They reported that the improvement is particularly high against Candida albicans which is important for a formulation whose potential use is against buccal infections.6
·  Yuri Ikeuchi-Takahashi et al., developed a matrix type mucoadhesive tablet for Indomethacin using a mixture of hard fat, ethylcellulose (EC) and polyethylene glycol (PEG) as a matrix base. They reported the tablets consisting of hard fat, EC and IMC, the drug release was sustained. In tablets consisting of hard fat, EC, considerable amounts of PEG and IMC, the drug release was relatively increased and IMC existed as the molecular phase or in an amorphous state. They suggested that the matrix type mucoadhesive tablet has good potential as a preparation for the treatment of pain due to oral aphtha.7
·  Luana Perioli et al., developed Metronidazole mucoadhesive tablets using different mixture of cellulose and polyacrylic derivatives in order to obtain new formulations containing for periodontal disease treatment. All tablets were characterized by swelling studies, ex vivo and in vivo mucoadhesive time, ex vivo mucoadhesion force, in vitro and in vivo release. Their studies revealed that best mucoadhesive performance and the best in vitro drug release profile were achieved by using hydroxyethyl cellulose (HEC) and carbomer 940 of 2:2 ratio.8
·  Hemanth H. Alur et al., evaluated the gum from Hakea gibbosa (Hakea) as a sustained-release and mucoadhesive component in buccal tablets following their application to the buccal mucosa of rabbits. Flat-faced core tablets containing either 22 or 32 mg of Hakea and Chlorpheniramine maleate (CPM) per tablet with either sodium bicarbonate or tartaric acid in a 1:1.5 molar ratio were formulated using a direct compression technique and were coated with Cutina® on all but one face. Their results demonstrate that the novel, natural gum, H. gibbosa, may not only be used to sustain the release of CPM from a unidirectional-release buccal tablet, but also demonstrated that the tablets are sufficiently mucoadhesive for clinical applications.9
·  Ahmad mahmood mumtaz et al., Studied the behaviour of bioadhesive buccal tablets prepared from different ratios of poly (acrylic acid-2,5-dimethyl-1,5-hexadiene) (PADH) and hydroxyl propyl methyl cellulose (HPMC) with and without triamcinolone acetonide (TAA) in the buccal cavities of healthy human volunteers. Their results indicate that tablets with a higher ratio of PADH swell faster, causing the disintegration of the tablets and consequently give rise to more rapid release of drug and the tablet with a PADH/HPMC ratio of 50:50 seems to provide a suitable compromise for good bioadhesion and prolonged release of drug.10
·  Ganesh P et al., formulated mucoadhesive buccal tablet of Domperidone to avoide first pass metabolism and to improve its bioavailability with reduction in dosing frequency. The mucoadhesive polymers used in the formulations were carbopol 934P, methocel K4M, methocelE15LV and chitosan. They concluded mucoadhesive drug delivery system for Domperidone could be achieved with prolonged effect by avoiding first pass metabolism.11
·  Keshavshetti G G et al., developed mucoadhesive buccal bilayer tablets of Atenolol to avoid first pass metabolism and to improve its bioavailability with reduction in dosing frequency, using HPMC 15cps and carbopol 934p as polymer They investigated that the addition of carbopol 934p increases the viscosity and swelling of tablets there by controls the release of drug and improves the mucoadhesive properties.12
·  Dashsrath M patel et al., formulated bioadhesive buccal tablets of Repaglinide using HPMC K15M as a sustained release polymer, chitosan as a bioadhesive polymer and ethyl cellulose as an impermeable backing layer, The tablets were evaluated using various parameters, and they concluded that the development of bioadhesive buccal drug delivery of Repaglinide tablets is one of the alternatives routes of administration to avoid first pass metabolism and provide prolonged release.13
·  Tahvilian Reza et al., Investigated mucoadhesive buccal tablets of Clotrimazole using various polymers like HPMC 4-M, SCMC. They reported increasing HPMC concentrations resulted in decreasing the swelling index and increasing surface pH.14
·  Satya brata bhanja et al., formulated mucoadhesive buccal tablets containing antidiabetic drug, Glimepiride to circumvent the first pass effect and to improve its bioavailability with reduction in dosing frequency and dose related side effects. They developed with varying concentrations of polymers like Carbopol 934P, HPMCK4M and Chitosan.15
·  Basanta kumar behera et al., fabricated mucoadhesive buccal drug delivery systems of Rosiglitazone maleate using mucoadhesive polymers like carbopol 934P and HPMC. The tablets were evaluated using different parameters, so they concluded it is best formulation that exhibited satisfactory bucoadhesive properties in comparison to other formulations.16
·  Satya brata bhanja et al., formulated mucoadhesive buccal tablets containing antihypertensive drug Timolol maleate by direct compression method of varying concentrations of polymers like carbopol 934, polyethylene oxide and hydroxy propyl methyl cellulose.17
·  Sellappan Velmurugan et al., prepared mucoadhesive buccal tablets of Glipizide using different mucoadhesive polymers such as carbopol 940, sodium alginate and HPMC K15M in combination. They concluded that mucoadhesive buccal tablets of Glipizide may be a good choice to bypass the hepatic first pass metabolism with an improvement in the bioavailability of Glipizide through buccal mucosa.18
·  Ganesh G.N.K et al., formulated buccoadhesive tablets of Labetalol hydrochloride using natural mucoadhesive polymer as xanthan gum. They concludes that formulated labetalol hydrochloride buccal tablets showed a significant increase in oral bioavailability compared to pure drug suspension and it can be successfully penetrated thoursough the buccal mucosa.19
ENCLOSURE-III
6.3 OBJECTIVE OF STUDY:
The specific objective of the study is to formulate and evaluate the mucoadhesive
buccal tablet with suitable polymer. The work will be scheduled as:
·  To study the preformulation factors of Gliclazide such as solubility, melting point, PH, PKa, λ max, and standard calibration curve of drug.
·  To study the drug-polymer compatibility.
·  To study the pre-compression parameters like bulk density, tapped density, angle of reapose, Carr’s index and Haunsner ratio for prepared tablet formulation.
·  To evaluate the mucoadhesive buccal tablets.
·  To carryout short term stability studies on the optimized formulation.
.
MATERIALS AND METHODS:
DRUG: Gliclazide.
POLYMER: Carbopol, Hydroxy propyl methyl cellulose, Sodium Alginate,Poly vinyl
pyrollidone( PVP) or any other suitable polymer etc.,
METHOD:
Devolopment of mucoadhesive buccal tablets of Gliclazide by using direct
compression method or any othe suitable method.
EVALUATION:
1. Hardness
2. Friability
3. Weight variation
4. Drug content
5. Surface pH study
6. Swelling index
7. Mucoadhesive strength
8. In vitro drug release.
ENCLOSURE - IV
7.1 SOURCE OF DATA:
1.  Research publications.
2.  International and Indian Journals.
3.  Textbooks and reference books.
4.  RGUHS Library.
5.  Library: Bharathi College of Pharmacy.
JOURNAL.
·  International Journal of pharmaceuticals.
·  Journals of controlled release.
·  European Journal of Pharmaceutics and Biopharmaceutics.
·  Indian Journal of pharmaceutical education and research.
·  International Journal of Biopharmaceutics.
·  International Journal of pharmacy and pharmaceutical sciences.
·  Research Journal of pharmaceutical and technology.
·  Asian Journal of pharmaceutics.
·  World journal of pharmaceutical research.
·  Inter national Journal of pharmaceutical Investigation.
·  International Journal of pharmacy and Biological sciences.
·  International Journal in pharmaceutical and Biomedical research.
INTERNET BROWSING:
http://www.google.com
http://www.rxlixt.com
http://www.pubmed.com
http://www.wikipedia.com
http://www.drugbank.com
http://www.medline.com
http://www.rguhs.ac.in
ENCLOSURE - V
7.2 Method of collection of data:
The data required for the study would be collected from the laboratory-based work planned as follows:
·  From literature.
·  Laboratory based studies includes.
Ø  Study for drug polymer interaction using FTIR.
Ø  Formulation of Gliclazide buccal tablet by suitable method.
Ø  And also data will be collected from the prepared formulation, then subjecting the formulation to different evaluation parameters like in-vitro mucoadhesion, Assay of drug content, Content uniformity, Swelling studies, in-vitro release studies, Stability studies on the selected formulation.
ENCLOSURE- VI
7.3- Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, Please describe briefly.
-NO-
7.4 - Has ethical clearance been obtained from your Institution in case of 7.3?
-NOT APPLICABLE-
ENCLOSURE – VII
BIBLIOGRAPHY
1.  Swamy P.V, Kinagi M. B, Biradar S. S, Gada S et al., Formulation design and evaluaton of bilayer buccal tablets of Granisetron hydrochloride. Ind J Pharm Edu Res,2011;45(3):242-247.