“FORMULATION AND EVALUATION OF
FAST DISINTEGRATING TABLET OF FENOFIBRATE”
SYNOPSIS FOR
M-PHARM DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BENGALURU, KARNATAKA
SUBMITTED BY
MUNDRU RAVI TEJA
DEPARTMENT OF PHARMACEUTICS
UNDER THE GUIDANCE OF
Dr. Prof.KALYANI PRAKASM.M.Pharm Ph.D
THE OXFORD COLLEGE OF PHARMACY
HONGASANDRA, BENGALURU-68
KARNATAKA
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BENGALURU, KARNATAKA
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR
DISSERTATION
1. / Name of the Candidateand Address /
MUNDRU. RAVI TEJA
A. POSTAL ADDRESSTHE OXFORD COLLEGE OF PHARMACY,
NO.6/9,1ST CROSS,
BEGUR MAIN ROAD,HONGASANDRA,
BENGALURU- 68, KARNATAKA.
B. PERMANENT ADDRESS
S/O. BRAHMAM,
H.NO. 3-40-18,1ST LINE, N.G.O COLONY,
NARASARAOPET, GUNTUR(Dist)
ANDHRA PRADESH-522601.
2. /
Name of the Institute
/ THE OXFORD COLLEGE OF PHARMACYNO.6/9, 1ST CROSS,
BEGUR MAIN ROAD, HONGASANDRA,
BENGALURU-68, KARNATAKA.
3. /
Course of Study and Subject
/ Master in Pharmacy[Pharmaceutics]
4. /
Date of Admission to Course
/ 18/10/ 20105. / Title of the Topic:
“FORMULATION AND EVALUATION OF FAST DISINTEGRATING TABLET OF FENOFIBRATE”
6. / BRIEF RESUME OF THE INTENDED WORK:
6.1 Need for study:
§ Hyperlipidemia is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood.
§ Hyperlipidemia is characterized mainly by increased serum VLDL(very-low-density lipoprotein) content accompanied by high triglyceride concentration.
§ Hypolipidemic drugs are the drugs which lower the levels of lipids and lipoproteins in blood.
§ Fibric acid derivatives or Fibrates are the class of Hypolipidemic drugs which are used mainly for reducing the elevated levels of triglycerides.
§ Fenofibrate is a drug of the fibrate class. Treatment with fenofibrate results in a substantial reduction in plasma cholesterol and triglycerides, and is usually associated with a moderate decrease in low density lipoprotein (LDL) cholesterol and an increase in high-density lipoprotein (HDL) cholesterol concentrations.
§ Fenofibrate is available as tablets for oral administration. Each tablet contains 40mg or 120mg fenofibrate.
§ The brand names of medications containing fenofibrate are Tricor, Lipofen, Antara, Lofibra.
§ Oral route is the most preferred route for administration of various drugs because it is regarded as safest, most convenient and economical. Recently researcher developed the fast disintegrating tablets with improved patient compliance and convenience1.
§ Fast disintegrating tablets are solid dosage forms which dissolve rapidly in saliva without chewing and additional water2.
§ Fast disintegrating tablets overcome the disadvantages of conventional dosage form especially dysphagia (difficulty in swallowing) in paediatric and geriatric patients3.
§ Fenofibrate is slightly soluble in water. The poor aqueous solubility of the drug leads to variable dissolution rates.
§ To enhance the solubility and dissolution rate, Fenofibrate can be formulated as fast disintegrating tablet using superdisintegrants.
.
6.2 Review of Literature:
1. The main objectives of the study were to develop and evaluate an optimal self-microemulsifying drug delivery system formulation containing Fenofibrate and to assess its pharmacodynamic effect in terms of lipid lowering potential. It is reported that absorption of Fenofibrate is increased by ~35% when it is administered with food ratherthan in a fasting state. Thus, formulating a lipid-based system of Fenofibrate can be viewed as an option for improving its oral bioavailability4.
2. The objective of the present investigation was to improve the solubility and the dissolution rate of Fenofibrate (FNO), a poorly water-soluble drug by solid dispersion technique using a water-soluble carrier, Poloxamer 407 (POL). The lyophillization technique was used to prepare solid dispersions. The differential scanning calorimetry and x-ray diffraction studies demonstrated that enhanced dissolution of FNO from solid dispersion might be due to a decrease in the crystallinity of FNO in lyophilized POL during solid dispersion preparation5.
3. The purpose of present study is to develop a new, simple, single step melt solidification technique for hypolipidemic agent Fenofibrate. The melt solidified beads were prepared by two techniques. The first method involves melting the drug and cooling the melt. In second method, the drug melt was poured in the water stirred at optimum speed to obtain beads. In vitro dissolution studies of melt solidified beads showed slower dissolution rate which might be due to compactness and higher bond strength of the beads6.
4. Aim of this work was to enhance dissolution rate of Fenofibrate (anti-hyperlipidaemia) by Ternary solid dispersion. In present work three components: Drug, Carrier (PEG-6000, PVP K-30, Citric Acid) & Surfactant (Poloxamer 188, Gelucire 44/14, and Transcutol-P) were used to prepare Ternary solid dispersion. A solvent evaporation method was used to prepare solid dispersion. Results have been shown that the Ternary Solid Dispersions have higher dissolution rate and stability then Binary (Simple) Solid dispersion7.
5. The aim of present work is to develop and validate spectrophotometric methods for the determination of Fenofibrate, an anti-hyperlipidemic, fibric acid derivative in pharmaceutical formulation. Methanol was used as a solvent throughout the study. Quantitative determination of fenofibrate in pharmaceutical formulation was carried out by UV-spectrophotometric method using absorbtivity values at 287.5 nm and by comparison with standard (method 1a and 1b) and the first order derivative absorbance values at 249.2 nm were utilized for estimation of drug (method 2). The method showed high specificity in the presence of formulation excipients and good linearity in the concentration range of 0-60 μg/ml8.
6. This work was aimed to formulate modified release Carvedilol tablets using two different super disintegrants by wet granulation method. The formulations were evaluated for hardness, friability, content uniformity, disintegration time and dissolution rate test. It was observed that superdisintegrant (Croscarmellose sodium) showed better results when added in the form of drug- superdisintegrant dispersion prepared by solvent evaporation when compared to direct addition to the formulation in wet granulation. Carvedilol fast dissolving tablet prepared by using dispersion which added 100% intragranularly showed rapid dissolution rate and 100% of drug was released only in 30min.The results clearly indicated the usefulness of the fast disintegrating tablet in the improvement of dissolution rate of poorly soluble drugs like Carvedilol whose bioavailability is dissolution rate limited9.
7. This work was aimed to formulate oro dispersible tablets of Ondansetron Hydrochloride by direct compression using superdisintegrants. The obtained tablets are evaluated for uniformity of weight, hardness, friability, Invitro disintegration time, wetting time, dissolution study. The tablets disintegrated rapidly in oral cavity and had acceptable hardness and friability. In vitro drug release from the tablets shows significantly improved drug dissolution10.
8. This work was aimed to formulate fast disintegration tablet of Aceclofenac by sublimation method employing Crospovidone and Sodiumstarch glycolate as superdisintegrants in different ratio along with up to 30 % w/w of camphor as a subliming agent. A total of six formulations and a control formulation F0 (without super-disintegrants) were designed. The obtained tablets are evaluated for weight variation, thickness, drug content uniformity, hardness, friability, disintegrating test, wetting time, water absorption ratio, Invitro drug release studies. It is observed that the disintegration time of the tablets had no effect (P>0.05) with increasing level of crospovidone. However, disintegration time increased (P<0.05) with increase in the level of sodium starch glycolate in the tablets. These results suggest that the disintegration times can be decreased by using wicking type of disintegrants (crospovidone)11.
9. This work was proposed to prepare directly compressible orally disintegrating tablets of Piroxicam using super disintegrants. Effect of varying concentrations of different superdisintegrants such as crospovidone, croscarmellose sodium, and sodium starch glycolate on disintegration time was studied. Tablets were evaluated for weight variation, thickness, hardness, friability, drug content, In vitro disintegrating time, wetting time and in vitro drug release. Release of drug was quick from formulations containing7% crospovidone (F8) compared to the other orally disintegrating tablet prepared12.
10. This work was aimed to develop mouth dissolve tablets of Nimesulide using vaccum drying technique. Granules containing nimesulide, camphor, crospovidone, and lactose were prepared by wet granulation technique. Tablets were first prepared and later exposed to vacuum. The tablets were evaluated for percentage friability, wetting time, and disintegration time. The results of multiple linear regression analysis revealed that for obtaining a rapidly disintegrating dosage form, tablets should be prepared using an optimum concentration of camphor and a higher percentage of Crospovidone13.
11. This work was proposed to study enhancement of the dissolution profile of Valdecoxib using solid dispersion with PVP. It also describes the preparation of fast-dissolving tablets of Valdecoxib by using a high amount of superdisintegrants. Poly vinyl pyrrolidone (PVP K-30) was selected and solid dispersions were prepared by the method of kneading. Dissolution studies using the USP paddle method were performed for solid dispersions of Valdecoxib. Tablets were formulated containing solid dispersion products and compared with commercial products. Tablets containing solid dispersion exhibited better dissolution profile than commercial tablets14.
12. This work was aimed to prepare fast disintegrating tablets of Lorazepam by effervescent method. They investigated the combined effect of two formulation variables: amount of crospovidone and mixture of sodium bicarbonate, citric acid, tartaric acid (effervescent material) on Invitro dispersion time. The tablets were evaluated for hardness, friability, thickness, drug content uniformity and Invitro dispersion time. The optimized tablet formulation was compared with conventional marketed tablet for drug release profiles. This formulation showed nearly eleven-fold faster drug release (t(50%) 2.8 min) compared to the conventional commercial tablet formulation (t(50%) >30 min)15.nnnnn
7. / 6.3 Objective of study:
The present work is an attempt to,
Ø Formulate a fast disintegrating tablet of Fenofibrate using superdisintegrants by direct compression method.
Ø Characterization of the tablet for sufficient mechanical integrity, content uniformity and invitro dissolution rates.
Ø Evaluation of tablets for tablet properties and performing stability studies
MATERIALS AND METHODS:
Drug : Fenofibrate
Excipent: Superdisintegrants(Croscarmellose sodium, Crospovidone, Sodiumstarch glycolate), PEG, HPMC, Flavouring agents, colourants.
Methods : Direct compression
7.1 Source of Data:
The data required for the work will be collected from different books , journals and articles available in The oxford college of Pharmacy, Journals available at Jgate @Helinet of the Rajiv Gandhi University of Health sciences website and through various internet sources .
7.2 Method of Collection of Data:
The solid dosage forms are performed by two phases. They are as follows
a) Preformulation study and
b) Evaluation study
Ø Preformulation studies which include:
Ø Design of the tablet dosage form,using optimisation techniques.
Ø Formulation of six desirable batches, amd check for reproducibility of Process parameters
1. Compatibility
2. Particle size analysis
3. Flow property of the granules
4. Compressibility and Hausner ratio.
Ø In case of tablet evaluation following studies are involved:
1. General appearance
2. Size and shape
3. Organoleptic properties
4. Hardness test
5. Friability test
6. Weight variation test
7. Content uniformity
8. Disintegration test and Dissolution test
9. Short term Stability studies
10. Comparative study with that of the marketed products.
7.3 Does the study require any investigation or interventions to be conducted on patients or the human or animals? If so please describe briefly:
Not applicable
7.4 Has ethical clearance been obtained from your institute
Not applicable
8. / List of References:
1. Puttalingaiah L, Kavitha K, TM Tamizh. Fast disintegrating tablets: An overview of formulation, technology and evaluation. Research Journal Pharmaceutical, Biological and Chemical Sciences 2011;2(2):589-601.
2. Venkateswarlu BS, Chandira RM, Ajay T, Bhowmik D, Chiranji B, Jayakar B, Sampath Kumar KP. Formulation Development and Evaluation of Fast Dissolving Tablets of Carvedilol. Journal Chemical and Pharmaceutical Research 2010;2(1):196-210.
3. Velmurugan S, Vinushitha S. Oral Disintegrating Tablets: An Overview International journal of Chemical and Pharmaceutical Sciences2010;1(2):1-12.
4. Patel AR, Vavia PR. Preparation and In Vivo Evaluation of SMEDDS (Self-Microemulsifying Drug Delivery System) Containing Fenofibrate. The AAPS Journal 2007;9(3):344-52.
5. Patel Tejas, Patel LD, Adeshara SP, Patel Timir, Makwana Sunil, Patel Tushar. Dissolution Enhancement of Fenofibrate by Solid Dispersion Technique. Current Pharma Research 2011;1(2):127-134.
6. Karmarkar AB, Gonjari ID, Hosmani A, Dhabale PN, Bhise BS. Use of Melt Solidification Technique for Preparation of Fenofibrate Beads: A Technical Note Digest Journal of Nanomaterials and Biostructures 2009 june;4(2):291 – 97.
7. Patel SK, Dr. Solanki AB, Dr.Parikh JR. Enhancement of rate of Dissolution of Fenofibrate by Ternary Solid Dispersion. IJPI’s Journal of Pharmaceutics and Cosmetology 2010;1(1):1-11.
8. Gupta KR, Askarkar SS, Rathod PR and Wadodkar SG. Validated spectrophotometric determination of Fenofibrate in Formulation. Der Pharmacia Sinica 2010;1(1):173-78.
9. Kumar UV, Naik VV, Rao YN, Reddy GN and Chowdary KPR. Formulation and Evaluation of Modified Release Carvedilol Tablets. An International Journal of Advances In Pharmaceutical Sciences 2010;1(1):83-87.
10. Gosai AR, Patil SB and Sawant KK. Formulation and Evaluation of Oro Dispersible Tablets of Ondansetron Hydrochloride by Direct Compression using Superdisintegrants. International Journal of Pharmaceutical Sciences and Nanotechnology 2008;1(1):106-11.
11. Gaur K, Tyagi LK, Kori ML, Sharma CS, Nema RK. Formulation and Characterization of Fast Disintegrating Tablet of Aceclofenac by using Sublimation Method. International Journal of Pharmaceutical Sciences and Drug Research 2011;3(1):19-22.
12. Prajapati BG, Bhaskar Patel. Formulation, Evaluation and Optimization of Orally Disintegrating Tablet of Piroxicam. International Journal of PharmTech Research 2010;2(3):1893-99.
13. Gohel M, Patel M, Amin A, Agrawal R, Dave R, Bariya N. Formulation Design and Optimization of Mouth Dissolve Tablets of Nimesulide Using Vacuum Drying Technique. AAPS PharmSciTech 2004;5(3):1-6.
14. Modi A, Tayad P. Enhancement of Dissolution Profile by Solid Dispersion (Kneading) Technique. AAPS PharmSciTech 2006;7(3):1-6.
15. Shirsand SB, Suresh S, Jodhana LS. Formulation design and optimization of fast disintegrating Lorazepam tablets by effervescent method. Indian J Pharm Sci. 2010 Jul;72(4):431-6.
9. / Signature of the Candidate /
MUNDRU RAVI TEJA
10. / Remarks of the Guide:
11. / Name and Designation of
11.1 Guide: / Dr.prof.KALYANI PRAKASAM
PROFESSOR & HOD
DEPT OF PHARMACEUTICS.
11.2 Signature of Guide:
11.3 Co Guide: / -NA
11.4 Signature of Co Guide: / -NA
11.5 Head of Department: / Dr.prof.KALYANI PRAKASAM
PROFESSOR & HOD
DEPT OF PHARMACEUTICS.
11.6 Signature of HOD:
12. / 12.1 Remarks of the Principal:
12.2 Signature of Principal: / [Dr. PADMAA M PAARAKH]
11