RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,



“FORMULATION AND EVALUATION OF ORO-DISPERSIBLE TABLETS OF AMLODIPINE BESYLATE”

SYNOPSIS FOR

M.PHARM DISSERTATION

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

KARNATAKA

[pic]

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

| | |ALEAKHYA.K. |

|1. |NAME OF THE CANDIDATE AND ADDRESS |DEPT. OF PHARMACEUTICS, |

| | |PES COLLEGE OF PHARMACY, |

| | |HANUMANTHA NAGAR |

| | |BANGALORE -50 |

| | |aleakhyak@ |

| | | |

| | |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 PHARMACY |

| | |HANUMANTH 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. |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. |

| | |

| | |

| | |

| | |

| |REVIEW OF LITERATURE: |

| | |

| |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 |

| | |

| |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 |

| | |

| | |

| | |

| |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 |

| | |

| |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 |

| | |

| |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 |

| | |

| |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 |

| | |

| |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 |

| | |

| |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 |

| | |

| |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 |

| | |

| |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 |

| | |

| |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 |

| | |

| |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 |

| | |

| |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: |

| |To carry out compatibility studies of drug and super disintegrants. |

| |To design and develop Oro-dispersible tablets of an anti hypertensive drug, Amlodipine Besylate. |

| |To carry out pre-compression and post-compression parameters. |

| |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: |

| | |

| |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. |

| | |

| |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. |

| | |

| |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. |

| | |

| |Bharadwaj V, Shukla V, Goyal N, Salim MD, Sharma PK. Formulation and evaluation of fast disintegrating sublingual tablets of|

|7. |Amlodipine besylate using different super disintegrants. Int J Pharm & Pharm Sci. 2010;2(3):89-92. |

| | |

| |Howida KI, Doaa AE-S. Valsartan Orodispersible Tablets: Formulation, in vitro/in vivo characterization. AAPS Pharm Sci Tech. |

| |2010;2(1):189-96. |

| | |

| |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. |

| | |

| | |

| | |

| | |

| |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. |

| | |

| |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. |

| | |

| |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. |

| | |

| |Jain CP, Naruka PS. Formulation and evaluation of fast dissolving tablets of Valsartan. Int J Pharm & Pharm Sci. |

| |2009;1(1):219-26. |

| | |

| |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. |

| | |

| |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. |

| | |

| |Bandari S, Mittapalli RK, Gannu R, Yamsani MR. Oro-dispersible tablets: An overview. Asian J Pharm. 2008;2(1):2-11. |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

|8. | |

| | |

| | |(ALEAKHYA.K) |

|9. |SIGNATURE OF CANDIDATE | |

| | | |

| | | |

| | | |

|10. |REMARKS OF THE GUIDE |Recommended |

| | | |

|11 |NAME AND DESIGNATION OF: | |

| | |Dr. MANJULA TALLURI |

| |11.1 GUIDE: |Professor , |

| | |Department of Pharmaceutics, |

| | |P.E.S College of Pharmacy, |

| | |Bangalore-560050. |

| | | |

| |11.2 SIGNATURE: | |

| | | |

| |11.3 CO-GUIDE: | |

| | |-NOT APPLICABLE- |

| | | |

| | | |

| |11.4 SIGNATURE: | |

| | | |

| |11.5 HEAD OF THE DEPARTMENT: |Dr. SATISH C.S |

| | |Professor & Head, |

| | |Department of Pharmaceutics, |

| | |P.E.S College of Pharmacy, |

| | |Bangalore-560050. |

| | | |

| | | |

| |11.6 SIGNATURE: | |

| | | |

| | |Prof. Dr. S. MOHAN |

|12 |12.1 REMARKS OF THE CHAIRMAN& PRINCIPAL: |Principal & Director |

| | |P.E.S College of Pharmacy, |

| | |Bangalore-560050. |

| | | |

| | | |

| |12.2 SIGNATURE: | |

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download