“FORMULATION AND EVALUATION OF ORO-DISPERSIBLE TABLETS OF AMLODIPINE BESYLATE”
SYNOPSIS FOR
M.PHARM DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA
BY
ALEAKHYA. K.
I M.PHARM
DEPARTMENT OF PHARMACEUTICS
PES COLLEGE OF PHARMACY
BANGALORE-560050
(2011)
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA
ANNEXTURE –II
PROFORMA OF REGISTRATION OF SUBJECT OF DISSERTATION
1. / NAME OF THE CANDIDATE AND ADDRESS / ALEAKHYA.K.DEPT. OF PHARMACEUTICS,
PES COLLEGE OF PHARMACY,
HANUMANTHA NAGAR
BANGALORE -50
PERMANENT ADDRESS
D/O K.VENKATESWARA RAO,
SAI DEEPA ROCK DRILLS, PLOT NO. 106., PHASEII.,I.D.A.,CHERLAPALLY,
HYDERABAD-51
HYDERABAD- 51
2. /
NAME OF THE INSTITUTION
/ PES COLLEGE OF PHARMACYHANUMANTH NAGAR,
BANSHANKARI 1st STAGE,
BANGALORE-50
3. / COURSE OF THE STUDY AND SUBJECT / MASTER OF PHARMACY
IN PHARMACEUTICS
4. / DATE OF ADMISSION TO THE COURSE / 11th July 2011
5. / TITLE OF THE TOPIC:
“FORMULATION AND EVALUATION OF ORO-DISPERSIBLE
TABLETS OF AMLODIPINE BESYLATE”
6.
7.
8. / BRIEF RESUME OF THE STUDY:
6.1Need For the Study:
Hypertension is the term used to describe high blood pressure. Normal B.P is 120/80mmHg. Antihypertensives are a class of drugs that are used to treat hypertension. They are classified into Diuretics, Sympatholytics, Vasodilators, Calcium channel blockers, Angiotensin II receptor blockers, Potassium channel blockers.
Amlodipine besylate is a besylate salt of amlodipine, and is a long-acting calcium channel blocker. This is one of the popular and widely used drug which has gone off patent. The market size of this drug is 2 billion dollars. Presently, Amlodipine besylate is available only as tablets in 2.5, 5 and 10 mg for oral administration.
The basic pharmacokinetics of this drug are: It has a half-life of 30-50 hours, has a high protein binding of 95-98%, Bioavailability is 60-65% and undergoes slow but extensive hepatic metabolism.
Despite of its popularity, as Amlodipine is available only in tablet form, the drug is not found useful to certain population like geriatrics and hospitalized patients. Orally disintegrating technique is one which meets the need of such population and is also convenient and of patient compliance.
The present project work is planned for finding a best formulation that uses orally disintegrating technique for an antihypertensive drug. The aim of this study is to develop orally disintegrating tablet form of Amlodipine drug, challenges in formulation, evaluation methodologies and future aspects.
6.2 REVIEW OF LITERATURE:
Ø Jangam VK et al., formulated and evaluated oro-dispersible tablets of Carvedilol by direct compression using Lactose and super disintegrants like Crospovidone and Sodium starch glycolate. Complete dissolution was not observed due to insolubility of Carvedilol. So solid dispersion of Carvedilol was prepared using PVP K-30 and 2%, 5%, 10% and 15% super disintegrants. Crospovidone in the concentration of 15% gave faster disintegration time in 16 sec. and shows 100% drug release within 15 min. 1
Ø Kabra AO et al., aimed towards the formulation and in vitro evaluation of rapidly disintegrating tablets by direct compression technology using Captopril as a model drug. Rapidly disintegrating tablet of Captopril was formulated using three super disintegrants in different concentrations i.e. 4%w/w, 8%w/w and 12%w/w and one disintegrants having concentration i.e. 2% w/w/, 4% w/w and 6% w/w like Croscarmellose sodium, Crospovidone, Sodium starch glycolate and Indion 414. All the batches were prepared by direct compression method using the Cadmach Single punch tablet compression machine using 8 mm flat punch. Disintegration time and drug release were taken as the basis to optimize the immediate release tablet. Prepared tablets were evaluated for thickness, hardness, friability, uniformity of weight, disintegration time, wetting time and dissolution study. Crospovidone in the concentration of 12 % gave faster disintegration in 22 seconds and shows and 80% drug release in 10 min at gastric pH is selected as the optimized formulation. The selected formulation was subjected to stability
studies for thirty days which showed stability with regard to the release
pattern.2
Ø Senthil A et al., prepared orally disintegrating tablets of Metaprolol tartarate by direct compression method using different concentration of Crospovidone as super disintegrants and different diluents. Tablets were prepared with different diluents like Mannitol, Lactose, Dibasic calcium phosphate at different concentration and tablets were evaluated. The tablet containing 6%
Crospovidone and with spray dried lactose as a diluent was found to be the optimized combination due to its fast in vitro dispersion when compared to other formulations, with wetting time below 1minute.3
Ø Bharadwaj V et al., prepared fast disintegrating tablets of Amlodipine besylate by using super disintegrants Kollidon CL, Ac-Di-Sol and Sodium starch glycolate in varying concentrations 2%, 4%, 6%. Tablets were evaluated for weight variation, hardness, friability, disintegration time. Using the same excipients, the tablets were prepared by direct compression and evaluated. It was found that tablet prepared with Ac-Di-Sol showed average disintegration time of 16seconds in vitro that is faster than other super disintegrants used in the study.4
Ø Howida KI et al., developed Valsartan ODT at 40 mg dose using freeze drying technique and evaluated. Among the prepared 27 tablet formulas, formula no.6 containing 4:6 Valsartan: Mannitol and 2% Pectin was selected to be tested in vivo. Oral bioavailability of two 40mg Valsartan tablets were compared with the conventional tablets after administration of a single dose to four healthy volunteers. Valsartan was monitored in plasma by HPLC. Apparent rate of absorption of Valsartan from prepared tablets was significantly higher than conventional tablets.5
Ø Naik PS et al., developed Metaprolol succinate fast dissolving tablets by dry granulation using PVP in Isopropyl Alcohol as binder. Camphor and Ammonium Bicarbonate were used as subliming agents in 10% and 20%
concentration. Croscarmellose sodium (Ac-Di-Sol) and Sodium starch glycolate were used as super disintegrants (2%, 4%, 8%) separately. Sodium starch glycolate and Ac-Di-Sol hastens the disintegration of tablets due to its wicking action on contact with water. Both when used in combination have a synergistic effect on the disintegration time and dissolution of tablets.6
Ø Pandey S et al., developed taste masking ODT that showed rapid onset of action as the dosage form is disintegrated prior to reaching the stomach and is ideal for acute diseases like hypertension and heart failure. Lisinopril was chosen and the drug is slightly bitter in taste and produces non compliance to patients especially geriatric patients. It concluded that beta cyclodextrins were useful for masking the taste as well as enhancing the solubility of the drug. Super disintegrants were helpful in formulation of fast dissolving tablets. Croscarmellose sodium is suitable for the formulation of the ODT’s.7
Ø Bhowmik D et al., worked on the fundamental principle, used in the development of fast dissolving tablets that is used to maximize its pore structure. They have evaluated spray dried materials and plastic materials for development of such tablets. Vaccum drying and freeze drying techniques have been tried to maximize pore structure. Freeze drying yielded a fragile and hydroscopic product. So vaccum drying technique was adopted after adding subliming agent to increase the porosity of tablets and that the tablet disintegrates quickly.8
Ø Bhowmik D et al., prepared fast dissolving tablets of Telmisartan by using super disintegrants Crospovidone, Ac-Di-Sol and Sodium starch glycolate at three different concentrations of 5%, 7.5%, 10%. The tablets were prepared by direct compression method and the prepared blend and tablets were evaluated for their physicochemical properties and in vitro dissolution study. The evaluation studies were performed such as weight variation, thickness,
hardness, disintegrating time, wetting time, and in vitro drug release and stability study. The disintegration time of fast dissolving tablets were increased by the addition of concentration of super disintegrants.9
Ø Jain CP et al., developed fast dissolving tablets of Valsartan using different super disintegrants by direct compression method. Effect of disintegrant on disintegration behavior of tablet in artificial saliva, pH 5.8 was evaluated. Wetting time of formulations containing Crospovidone was least and tablets showed fastest disintegration. The drug release from the tablets increased with increasing concentration of super disintegrants and was found to be highest with formulations containing Crospovidone.10
Ø Raghavendra Rao N G et al., developed rapidly disintegrating Chlorthalidone oral tablets by direct compression using co-grinding and solid dispersion methods. The major problem with the drug is limited aqueous solubility which may hinder dissolution. So, the solid dispersions and co-grinding method were followed to increase solubility and bioavailability. The tablet formulation containing Polyvinyl pyrrolidine K-12 solid dispersion showed maximum drug release than Chlorthalidone Polyvinyl pyrrolidine K-12 co-grinding method. The dissolution profile of best solid dispersion formulation was compared with co-grinding method formulation. The prepared tablets were evaluated for hardness, friability, wetting time, disintegration time, and in vitro drug release. The study revealed that solid dispersion of the drug with the hydrophilic carrier Polyvinyl pyrrolidine can enhance the dissolution rate of Chlorthalidone tablets.11
Ø Ranch KM et al., developed oro-dispersible tablets of Atenolol by using Camphor, Kyron-T314 and Lactose by direct compression technique. Tablets were evaluated for friability, wetting time and disintegration time. It was revealed that, tablets prepared using an optimum concentration of Camphor
and a higher % of Kyron-T314 disintegrated rapidly.12
Ø Bandari S et al., have given some of the ODT technologies available. They are - Lyophilization is a process that includes removal of solvent from a frozen suspension. The tablet has rapid disintegration and dissolution but has low mechanical strength and poor stability. Molding includes moistening, dissolving/dispersing the drug with a solvent and then molding the moist mixture into tablets. It results in high porous structure. They also have low mechanical strength. Cotton candy process involves formation of matrix of polysaccharides by the action of melting and spinning. It offers good mechanical strength. Sublimation involves the presence of highly porous structure in tablet matrix and offers good porosity and disintegration of tablet. Some other techniques are Zydis technology, Phase transition process melt granulation.13
6.3 Main objectives of the study:
1. To carry out compatibility studies of drug and super disintegrants.
2. To design and develop Oro-dispersible tablets of an anti hypertensive drug, Amlodipine Besylate.
3. To carry out pre-compression and post-compression parameters.
4. To carry out stability studies as per ICH guidelines.
MATERIALS AND METHODS:
7.1 Source of data:
The data will be obtained from the literature survey, internet source and experimental work, which includes formulation of Oro-dispersible tablets by using various super disintegrants, evaluation of pre-compression and post- compression parameters, evaluation of drug content and stability studies.
7.2 Method of collection of data (including sampling procedures if any)
The data will be collected from prepared formulations subjected to different evaluation techniques, estimation of water absorption ratio, wetting time, disintegration time, in-vitro drug release and stability studies.
7.3 DOES THE STUDY REQUIRE ANY INVESTIGATIONS 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-
LIST OF REFERENCES:
1. Jangam VK, Javvaji H, Tadikonda R, Gollapudi R. Formulation and in vitro evaluation of oro-dispersible tablets of Carvidilol. Int J Adv Pharm Sci. 2011;2(1):50-54.
2. Kabra AO, Shah FB, Wanare RS. Formulation and in vitro evaluation of rapidly disintegrating tablets using Captopril as a model drug. Int J Pharm Sci Rev Res. 2011;7(2):206-10.
3. Senthil A, Hima Bindu S, Thakkar HKRB, Jamsheer AK, Vontoor BN. Development and evaluation of orally disintegrating tablets of Metoprolol tartarate by direct compression method using different diluents. Int Res J Pharm. 2011;2(1):118-25.
4. Bharadwaj V, Shukla V, Goyal N, Salim MD, Sharma PK. Formulation and evaluation of fast disintegrating sublingual tablets of Amlodipine besylate using different super disintegrants. Int J Pharm & Pharm Sci. 2010;2(3):89-92.
5. Howida KI, Doaa AE-S. Valsartan Orodispersible Tablets: Formulation, in vitro/in vivo characterization. AAPS Pharm Sci Tech. 2010;2(1):189-96.
6. Naik PS, Kurup NS. Design and optimization of fast dissolving tablets containing Metaprolol by sublimation method. Int Res J Pharm. 2010;1(1):346-57.
7. Pandey S, Viral D, Goyani M. Formulation and evaluation of taste masked fast disintegrating tablets of Lisinopril. Int J Pharm Tech Res. 2010;2(2):1639-43.
8. Bhowmik D, Chiranjib, Jaiswal J, Dubey V, Chandira M. Fast dissolving tablet: A review on revolution of novel drug delivery system and new market opportunities. Der Pharmacia Lettre. 2009;1(2):262-76.
9. Bhowmik D, Jayakar B, Sampath Kumar K. Design and characterisation of fast dissolving tablet of Telmisartan. Int J Pharm Recent Res. 2009;1(1):31-40.
10. Jain CP, Naruka PS. Formulation and evaluation of fast dissolving tablets of Valsartan. Int J Pharm & Pharm Sci. 2009;1(1):219-26.
11. Raghavendra Rao NG, Kota RK, Setty CM, Purushotham Rao K. Formulation and evaluation of fast dissolving Chlorthalidone tablets. Int J Pharm & Pharm Sci. 2009;1(1):79-87.
12. Ranch KM, Koli AR, Bhavin VA, Parikh RK, Vyas RB, Maniyar NR, Modi JG. Formulation, design and optimization of oro-dispersible tablets of Atenolol. Int J Pharm Tech Res. 2009;1(4):1559-63.
13. Bandari S, Mittapalli RK, Gannu R, Yamsani MR. Oro-dispersible tablets: An overview. Asian J Pharm. 2008;2(1):2-11.
9.
/SIGNATURE OF CANDIDATE
/ (ALEAKHYA.K)10. / REMARKS OF THE GUIDE / Recommended
11 / NAME AND DESIGNATION OF:
11.1 GUIDE: / Dr. MANJULA TALLURI
Professor ,
Department of Pharmaceutics,
P.E.S College of Pharmacy,
Bangalore-560050.
11.2 SIGNATURE:
11.3 CO-GUIDE:
11.4 SIGNATURE: / -NOT APPLICABLE-
11.5 HEADOFTHE DEPARTMENT: / Dr. SATISH C.S
Professor & Head,
Department of Pharmaceutics,
P.E.S College of Pharmacy,
Bangalore-560050.
11.6 SIGNATURE:
12 / 12.1REMARKSOFTHE CHAIRMAN& PRINCIPAL: / Prof. Dr. S. MOHAN
Principal & Director
P.E.S College of Pharmacy,
Bangalore-560050.
12.2SIGNATURE:
2