BANGALORE, KARNATAKA
ANNEXURE I
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1 / NAME OF THE CANDIDATE AND ADDRESS / Mr. MAHENDRAKUMAR NANJIBHAI DHAMELIYA
DEPARTMENT OF PHARMACEUTICS,
MARATHA MANDAL’S
COLLEGE OF PHARMACY,
BELGAUM- 590016, KARNATAKA.
2 / NAME OF THE INSTITUTION / MARATHA MANDAL’S
COLLEGE OF PHARMACY
BELGAUM-590016, KARNATAKA.
3 / COURSE OF THE STUDY
SUBJECT / MASTER OF PHARMACY
(PHARMACEUTICS)
4 / DATE OF ADMISSION / DECEMBER 2011
5 / TITLE OF THE PROJECT :-
“ DESIGN ANDEVALUATION OF MOUTH DISSOLUTION TABLET CONTAINING MONTELUKAST SODIUM AND LEVOCETRIZINE DIHYDROCHLORIDE”
BRIEF RESUME OF INTENDED WORK:-
6.1
6.2
6.3 / NEED FOR THE STUDY:-
Mouth dissolving drug delivery system [MDDS]are a new generation of formulations which combine the advantage of both liquid and conventional tablet formulation.This segment of formulation is especially designed for dysphagic, geriatric, pediatric,bed–ridden travelling and psychotic patient who are unable to swallow conventional oral formulation.[1] The concept of mouth dissolving tablets emerged with an objective to improve patient’s compliance. These dosage forms rapidly disintegrate and/or dissolve to release the drug as soon as they come in contact with saliva, thus obviating the need for water during administration, that makes them highly attractive for paediatric and geriatric patients. Difficulty in swallowing conventional tablets and capsules is common among all age groups, especially in elderly and paediatric patients.Elderly patients may find the administration of the conventional oral dosage forms difficult as they regularly require medicines to maintain a healthy life. Children may also have difficulty in ingesting because of their under developed muscular and nervous systems. These problems can be resolved by means of Mouth Dissolving Tablets (MDTs)[2]
The faster the tablet disintegration in to solution, the quicker the absorption and onset of action. Some drugs are absorbed from the mouth, pharynx and esophagus as saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than those observed from conventional tablets dosage form. Hence, in the present study an attempt will be made to formulate mouth dissolving tablets, with a view to develop a convenient means of administration to those patients suffering from difficulties in swallowing, nausea and motion sickness[3].
The US food administration centre for drug evaluation and research(CDER) defines , in the ‘Orange Book’ an MDT as “a solid dosage form containing medicinal substances , which disintegrate rapidly[4],usually within a matter of second when placed upon the tongue. The significance of these dosage forms is highlighted by the adoption of the term “Orodispersible Tablet” ,by the European pharmacopoeia which describes it as a tablet that can be placed in oral cavity where it disperse rapidly before swallowing[4].
Mouth dissolving tablets are also called as fast dissolving tablets, fast-melting, melt-in mouth tablets, orodispersible tablets, rapimelts, porous tablets, quick dissolving etc. The concept of melt in mouth dissolving tablet is developed, tablet that disintegrate in saliva, without need of drinking water within 15 to 60 seconds which offers fast absorption & then onset of action. According to European pharmacopoeia, the MDT should be disperse/disintegrate in less than three minutes[5].
Choice of drug candidate:-
- Suitable drug candidate for mouth dissolution tablet should posses no bitter taste, good stability in water and saliva , dose should be as low possible, Small to moderate molecular weight.
A wide range of drugs can be considered as a candidate for this dosage form. [E.g. NSAIDS, Anti ulcer, Anti histaminics, Hypnotics and sedative, Antipsychotics, Anti depressant, Antiparkinsons, antimigrain, antiemetics,antifungal, antimalarial,diuretic, gastro-intestinal agents,local anaesthetics etc.[6]
Asthma ,chronic pulmonary obstructive pulmonary diseases & allergic rhinitis are commonly encountered respiratory diseases, asthma is chronic diseases characterised by hyperresponsive airway, affecting 10 million patient [4 to 5% ]of the US population and resulting annually in 2 million emergency room visit 500,000 dealth. COPD is also called emphysema or chronic bronchits. Montelukast sodium is a potent, selective and orally acting leukotriene receptor antagonist that acts by inhibiting physiological actions of the cysteinyl leukotrienes(LTC4,LTD4and LTE4). It is used in the prophylaxis and treatment of asthma.Montelukast sodium is chemically designated as [R-(E)]-1-[[[1-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3 phenyl]propyl]thio]methyl] cyclopropaneacetic acid,monosodium salt, an orally administered drug of choice in the treatmentof asthma in adults and children. montelukast sodium is freely soluble in water, ethanol, methanol & insoluble acetonitrile, good stability in saliva, mol w.t is 587g/mol.[7]
Levocetrizine dihydrochloride is selective,long acting pheripheral H1receptor antagonist.allergic rhinitis is a symptomatic disorder of the nose induced by inflammation mediated by immunoglobulin E (IG E) in the membrane lining the nose after allergic explosure. It is prevent the release of other allergy chemicals and increase blood supply to the area. Levocetrizine dihydrochloride is soluble in watet,methanol & insoluble in acetone , mol w.t is 388g/ mol.[8]
REVIEW OF LITERATURE:-
Literature review for undertaking the study was done by referring published articles in various national and international journals, official standard books and to various websites on the internet.
- Kanakadurga devi Net al(2010), haveto prepare fastdisintegrating tablet of montelukast sodium with three superdisintegrants that is poly plasdonexl10 , Ac-disol, and primojel to enhance dissolution rate.the tablet were evaluated for hardness , tensil strength, drugcontent, friability,and were found satisfactory.based on dissolution rate the disintegrant can be rated as polyplasdone xl>10 Acdi-sol>primojel. Hence polyplasdone xl 10 was recommended as suitable disintegrate for the preparation of direct compression of montelukast sodium . it was conclude that the rapidly disintegrating tablet with proper hardness, rapid disintegration in oral cavity with enhanced dissolution rate can be made by using super disintegrants.[8]
- Ajay et al (2011), have designed and evaluation of mouth dissolution tablet of montelukast sodium using direct compression method. In this formulation using different superdisintigrate agent such as croscamellose sodium ,and crosspovidone.the formulation was subjected to pre compression and post compression parameter and result were found to be within acceptable limit and first order release kinetics.[9]
- Vijay Sharma et al (2012), have formulated and evaluation of taste masked mouth dissolution tablet of Levocetrizine hydrochloride by complex using tulsion -335 .thease tablet were formutated by wet granulation with pvp as binder, sodium starch glycolate ,& crosscramalose as super disintigrants. Prepared tablet were evaluated different parameter such as swelling time, resin activation, drug resin ratio as well as stirring time , %drug loading , infrared spectroscopy, thermal analysis & x -ray diffraction.all parameter within limit as well as good physicochemical property .drug release rate of formutated MDTs was found to higher as compared to conventional tablet.[10]
- Mahapatra et al (2009), have designed and characterization of mouth dissolving tablets ofLevocetirizine hydrochloride using sublimation technique. In this formulation using different concentrations of Perlitol SD 200 (spray dried mannitol) and menthol, mouth dissolving tablets were developed using direct compression technique. In the formulation, the wetting time or simulated saliva penetration was observed very fast, due to high porosity[11].
- Manish Kumar et al (2010), have fabricated and evaluation of fast dissolving drug delivery system containing Levocetrizine hydrochloride by direct compression technique. The prepared tablet were evaluated for thickness, uniformity of wt, content uniformity, hardness, friability, wetting time, in vitro drug release ,in vitro disintegration time. In conclusion , overall result suggests that the FDTS containing sodium bicarbonate and mannitol in the ratio 1:3[F4] Show best result in term of %drug release, compressibility index, hardness & disintegration time.[12]
- Sajalet al(2008),have formulated melt in mouth tablets of haloperidol by using combination of superdisintegrants, crosscarmellose sodium, sodium starch glycolate, and crospovidone by direct compression method. The formulated melt in mouth tablets were evaluated for various physicochemical parameters, disintegration time and for in vitro drug release. All the formulation had disintegration time less than 30s and release maximum amount of drug by 12 min. Formulation containing higher concentration of crosspovidone decreases disintegration time and optimize the drug release[13].
- Kumar et al(2009), have developed and characterized mouth dissolving tablets of fenofibrate using different subliming agents like camphor, thymol, ammonium bicarbonate and different concentrations of menthol using direct compression method. The tablet gives benefit in terms of patient compliance, low dosing, rapid onset of action, increased bioavailability, low side effect and good stability by enhancing the solubility[14].
- Bedi et al (2009), have formulated and evaluated mouth dissolving tablets of oxacarbazepin, is an anticonvulsant drug, mainly used as an first line treatment in adults and childrens. The tablets were prepared by using two different technology, direct compression and solid dispersion methods. The result compared for both technologies showed that the oxacarbazepin prepared using solid dispersion was found to have good properties [15].
- Rao et al(2009),have formulated and evaluated mouth dissolving tablets of metoprolol tartrate by sublimation method using camphor as subliming agent and different super disintegrant like crosscarmalose sodium, crospovidone, sodium starch glycolate, and prepared tablets evaluated for different parameter and results concluded that fast dissolving tablets of metoprolol tartrate showing enhanced bioavailability and effective therapy by using sublimation method[16].
- Sammour et al (2006), have formulation and evaluation of mouth dissolving tablets containing Rofecoxib Solid Dispersion. Rofecoxib is a NSAID used as a pain reliever. In this study increase the solubility and dissolution rate of rofecoxib by solid dispersion with polyvinyl pyrrolidin K30 using solvent evaporation method. The tablet is formulate by using different superdisintegrants like Crospovidone, Cross carmellose sodium, and Sodium Starch Glycolate [17].
- Sharma et al (2010), have design and optimization of mouth dissolving tablets of domperidone using sublimation technique. In this study tablet was prepared by using camphor and crospovidone by direct compression technique. Camphor was sublimed from these tablets by exposure to vacuum. The tablets were evaluated for percent friability and disintegration time[18].
- The proposed work is planned :-
levocetrizine dihydrochloride using different disintegrating agent.
To avoid first pass metabolism, gastric irritation, &gastric disturbance.
To improve bioavailability dissolution efficiency.
To improve patient compliance.
The proposed plan involves :-
To preformulation study.
To preparation of mouth dissolution tablet different super disintigrants.
To prepared tablet are subjected to various evaluation tests.
To stability study for optimizied formulation.
To compare the marketed product.
7 / MATERIALS AND METHODS
7.1
7.2 / Materials:
Suitable drug for the Mouth dissolving tablet will be selected from the following classes:-
- Anti-allergic.
- Antiasthmatic or any other miscellaneous or Suitable Drugs.
carmellose sodium, sodium starch glycolate, and any other
suitable excipients.
Method of Preparation :
Many techniques have been reported for the formulation of Mouth dissolving tablets. Any one from the following will be used for the formulation of Mouth dissolving tablets.
1.Direct compression
2.Tablet moulding
3.Sublimation or suitable methods
SOURCE OF DATA:-
The data will be collected from prepared formulations subjected to different evaluation techniques, scale-up techniques and stability studies obtained from ICH guidelines. this data is obtained from the formulated mouth dissolving tablet of different drugs.
Data is collected from:-
- RGUHS (Helinet), Bangalore.
- Indian Pharmacopoeia.
Review and Research articles
Research publications.
Textbooks and reference books.
COLLECTION OF DATA
Evaluation of blends:-
- Angle of repose.
- Bulk density.
- Tapped density.
- Hausner ratio.
Evaluation of Mouth Dissolving Tablets:-
1. General Appearance.
2. Size and Shape.
3. Uniformity of Weight.
4. Tablet Thickness.
5. Hardness.
6. Friability.
7. Drug Content Uniformity.
8. Wetting Time and Water absorption ratio.
9. Disintegration test.
10. Dissolution test.
11. Stability Studies.
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 clearance been obtained from your institution in case of 7.3?
-No-
8.0 / LIST OF REFERENCES:-
- Dali S, Subhashis C, Sanjay S,Brahmeshwar M .Mouth dissolution tablet II; an
- Shukla D, Chakraborty S, Singh S, Mishra B.Mouth dissolving tablets : an overview
- Jaysukh JH, Dhaval AR , Kantilal RV . Orally disintegrating tablet :a reviw .Tropical
- Hirani JJ, Rathod DA.Orally disintegrating tablets: a review. Tropical journal of
- Dureja K, Saini H. Mouth Dissolving Tablets: A Review. Indian drugs.2004;41(4):
- Wagh MA, Kothawade PD, Salunkhe KS, Chavan NV, Daga VR. Techniques used in
system. 2010;(2): 98-107.
- Richard AH, Pamela CC, Respiratory System. Wolters Kluwer. 4thEd Lippincott’s
8. Kanakadurga devi N,prameela rani A, Sai mradula B,formulation and evaluation of oral
Disintigrant tablet of montelukast sodium : effect of super disintigrants.JPR 2013 :3(4):
802-808.
9. Ajaykumar P, taqiuddin A, Nithin G ,Abhilash P, Maduri T, Supriya K, Formulalation
and evaluation of mouth dissolution tablet of montelukast sodium.RJPBCS volume 2
issue 3 page no 268-274.
10.Vijay S, Himanshu C, formulation and evaluation ot taste masked mouth dissolution
Tablet of levocetrizine hydrochloride ;Iranian journal of pharmaceutical research
(2012)11(2).
11.Mahapatra AK, Murthy PN, Sahoo J, Biswal S, Sahoo SK. Formulation design and
Optimization of mouth dissolution tablet of levocetrizine hydrochloride using
sublimation techniques. International journal of pharmaceutical education and
research.2009:43(1):39-45.
12. Manish K, Sharad V, Sazid A, Shikha A, Amit B. Preparation and evaluation of fast
Dissolving drug delivery system containing levocetrizine hydrochloride by direct
compression technique.IJPR Vol 2, suppl 3, 2010 ,page no ;109-111.
13.Sajal KJ, Vijayalakshmi P, Roopa K, Divakar G. Formulation and evaluation of melt
in Mouth tablet of haloperidol.asian journal of pharmaceutical.2008;2:255-260.
14. Kumar R, Patil S, Patil MB, Patil SR, Paschapur MS.Formulation and evaluation of
Mouth dissolution tablet of fenofibrate using sublimation techniques. International
journal of chem tech research. 2009; (1)4: 840-50.
15. Bedi N, Kalia A, Khurana S. Formulation and evaluation of mouth dissolving tablets
of oxacarbazepin. International journal of pharmacy and pharmaceutical sciences.
2009; ( 1):12-23.
16. Raghavendra Rao NG, Thube K, Suresh DK. Formulation and evaluation of mouth
dissolving tablets of metoprolol tartrate by sublimation method. International journal
of pharma and bio sciences, 2010;1(2):1-7.
17.Sammour OA, Hammad MA, Nagia AM, Ahmed SZ. Formulation and evaluation of
mouth dissolving tablets containing rofecoxib solid dispersion. American association
ofpharmaceutical scientist. 2006; 7(2): E1-E5.
18.Sharma S, Singh G, Gupta GD. Formulation design and optimization of mouth
dissolving tablets of domperidon using sublimation technique. International journal of
pharmaceutical sciences. 2010;(1):128-136.
9 / SIGNATURE OF THE CANDIDATE
10 / REMARKS OF THE GUIDE / The topic selected for dissertation is satisfactory. Adequate equipments and chemicals are available to carry out the project work.
11 / NAME AND DESIGNATION
11.1 / GUIDE / Dr. NAGESH C.M.Pharm, Ph.D.
ASSOCIATE PROFESSOR,
DEPARTMENT OF PHARMACEUTICS,
MARATHA MANDAL’S COLLEGE OF PHARMACY,
BELGAUM- 590016, KARNATAKA
11.2 / SIGNATURE
11.3 / CO-GUIDE / Dr. CHANDRASHEKHARA S M.Pharm, Ph.D.
ASSOCIATE PROFESSOR,
DEPARTMENT OF PHARMACEUTICS,
MARATHA MANDAL’S COLLEGE OF PHARMACY,
BELGAUM- 590016, KARNATAKA.
11.4 / SIGNATURE
11.5 / HEAD OF THE DEPARTMENT / Dr. NAGESH C.M.Pharm, Ph.D.
PRINCIPAL & HOD,
DEPARTMENT OF PHARMACEUTICS,
MARATHA MANDAL’S COLLEGE OF PHARMACY,
BELGAUM- 590016, KARNATAKA
11.6 / SIGNATURE
12 / 12.1 / REMARKS OF THE PRINCIPAL / All the required facilities will be provided to carry out dissertation work under the supervision of the Guide.
12.2 / PRINCIPAL / Dr. NAGESH C.M.Pharm, Ph.D.
PRINCIPAL,
DEPARTMENT OF PHARMACEUTICS,
MARATHA MANDAL’S COLLEGE OF PHARMACY,
BELGAUM- 590016, KARNATAKA
12.3 / SIGNATURE