Formulation and Evaluation of Curcumin Floating Matrix Tablets Using Natural Polymers

FORMULATION AND EVALUATION OF CURCUMIN FLOATING MATRIX TABLETS USING NATURAL POLYMERS

Synopsis for M.Pharm Dissertation submitted to the

Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka.

By

Mr. S. HARISH

M.Pharm., Part-I

Under the guidance of

Dr. C. JAYANTHI, M.Pharm., Ph.D.,

PROFESSOR AND HEAD,

DEPARTMENT OF PHARMACEUTICS

SARADA VILAS COLLEGE OF PHARMACY

KRISHNAMURTHYPURAM

MYSORE- 570004

2011-2012

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA, BANGALORE.

ANNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / NAME OF THE CANDIDATE
AND ADDRESS (IN BLOCK LETTERS) / S. HARISH
M. PHARM., PART –I
DEPARTMENT OF PHARMACEUTICS,
SARADAVILAS COLLEGE OF PHARMACY,
KRISHNAMURTHYPURAM, MYSORE-04
2. /

NAME OF THE INSTITUTION

/ SARADAVILASCOLLEGE OF PHARMACY,
MYSORE.
3. /

COURSE OF STUDY AND SUBJECT

/ MASTER OF PHARMACY IN PHARMACEUTICS.
4. / DATE OF ADMISSION OF COURSE / 15-12-2011
5. / TITLE OF TOPIC / FORMULATION AND EVALUATION OF CURCUMIN FLOATING MATRIX TABLETS USING NATURAL POLYMERS
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 studies require any investigations 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
9. / SIGNATURE OF CANDIDATE
10. / REMARKS OF GUIDE / RECOMMENDED
11. / NAME AND DESIGNATION OF
11.1 Guide
11.2 Signature
11.3 Co guide (If any)
11.4 Signature
11.5 Head of department
11.6 Signature
12.1 Remarks of the Principal
12.2 Name and designation of principal
12.3 Signature / Dr. C. JAYANTHI, M.Pharm., Ph.D.,
PROFESSOR AND HEAD
DEPARTMENT OF PHARMACEUTICS,
SARADA VILAS COLLEGE OF PHARMACY,
KRISHNAMURTHYPURAM, MYSORE – 04
Not applicable.
Not applicable.
Dr.C. JAYANTHI,M.Pharm., Ph.D.,
PROFESSOR AND HEAD
DEPARTMENT OF PHARMACEUTICS,
SARADAVILASCOLLEGE OF PHARMACY,
KRISHNAMURTHYPURAM, MYSORE –04
RECOMMENDED & FORWARDED
Dr. K. HANUMANTHACHAR JOSHI,
M.Pharm., Ph.D.,
PRINCIPAL,
SARADA VILAS COLLEGE OF PHARMACY,
KRISHNAMURTHYPURAM, MYSORE - 04
6.0
7.0 / BRIEF RESUME OF THE INTENDED WORK
ENCLOSURE-I
6.1 Need for the study
Oral controlled release drug delivery systems offer great advantages over the conventional dosage forms. A number of oral controlled release drug delivery systems such ashydro dynamically balanced drug delivery system (floating tablet), oral osmotically driven drug delivery systems (osmotic pump), pH controlled drug delivery system, etc.,have been investigated and commercialized.These systemsare found useful because ofimprovedpatient compliance due to reduction in the frequency of dosing, employ minimum drug, reduce fluctuation in drug level, and improve bioavailability of some drugs1.
Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, ant proliferative and antiangiogenic activities. PhaseI clinical trials have shown that curcumin is safe even at high doses (12g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn’s disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.2
. Poor water-solubility and bioavailability of curcumin drived us to explore the potential of floating matrix tablet technology to improve dissolution profile of curcumin using natural polymers.
ENCLOSURE-II
6.2 Review of literature
1.AroraShwetaet.al, Floating drug delivery system- A Review to develop an efficient floating drug delivery (FDDS) was to compile the recent literature with special focus on the principle mechanism of floatation to achieve gastric retention.3
2.Xiao QiangXuet.al, floating matrix dosage form for phenoporlamine HCL based on gas forming agent; In this work the in-vitro an in-vivo evaluation of formulation was done. Formulation showed increased bioavailability with good floating properties.4

Amit Pet.al,studied formulation development and evaluation of famotidine floating tablet. The purpose of this investigation was to prepare a floating drug delivery system of famotidine. Famotidine having poor absorption in acidic environment (upper GIT). When given orally, it shows the bioavailability near to 50%. To overcome these drawbacks, the present study was undertaken to investigate the floating dosage form of famotidine. Floating tablets were prepared using Direct Compression.5
Rabi Net.al, formulated and evaluated floating mucoadhesive tablets of metoprolol succinate were developed to prolong its release and improve bioavailability by avoidance of first pass metabolism during the treatment of chronic hypertension. Tablets were prepared by direct compression using directly compressible polymers such as HPMC K4M, HPMC K15M, sodium carboxy methyl cellulose and carbopol 940P and were evaluated for buoyancy test, mucoadhesion force, swelling study, drug content, ex-vivo mucoadhesion strength and in-vitro release profile. Results indicated that the release from the formulation containing 35 mg of HPMC K4M best fitted square root kinetics6.

Shweta Sharma et.al, Prepared Captopril floating matrix tablets with various grades of HPMC in varying ratios to formulate the floating tablets. Lactose was used as a diluent in the preparation of the tablets. Sodium bicarbonate was incorporated into the tablets to aid buoyancy of the tablets. it was concluded that the formulation F1 is the best formulations as the extent of drug release was found to be around 85 %7
Gupta SKet.al, Prepared floating tablets of Acyclovir containing polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and hydroxyl propyl methyl cellulose (HPMC) as the polymers and sodium bicarbonate as a gas generating agent, to reduce floating lag time and tablets were prepared by wet granulation method. On the basis of evaluation parameter formulation AV4 selected as developedformulation8.
Ramesh Bet.al, Developed Floating matrix tablets of norfloxacin to prolong gastric residence time, leading to an increase in drug bioavailability. Tablets were prepared by the wet granulation technique using polymers such as hydroxyl propyl methyl cellulose (HPMC K4M, HPMC K100M) and xanthan gum. Tablets were evaluated for their physical characteristics, viz., hardness, thickness, friability, and mass variation, drug content and floating properties. Further, tablets were studied for in vitro drug release characteristics for 9 hours9.
Raghavendra Rao NG et.al,Studied on cefixime gastric oral floating tablets for controlled release and increased gastric retention time. Different excipients were used are (sodium bicarbonate), swelling agent (cross linked CMC), viscolyzing agent (xanthan gum, guar gum) and a gel forming polymer (sodium alginate), Also contains an additional hydrophilic polymer (HPMC K4M, and HEC).The cefixime floating tablets were prepared by direct compression method. The prepared tablets were subjected to post-compressional analysis for the parameters such as hardness, friability, weight variation, thickness, drug content, lag time subsequently buoyancy time, and in vitrodissolution studies10.

3.Jaimini M.et.al, Formulation and Evaluation of Famotidine floating tablets was reported. Different grades of Methocel K100 and Methocel K15M were used for gel forming properties, sodium bicarbonate was incorporated as gas generating agent. The drug release from the tablet was sufficiently sustained and non-Fickian transport of drug from tablets was confirmed.11
4.ZiyaurRahmanet.al, prepared bilayer floating tablets (BFT) for captopril using different compression technology. HPMC, K-grade and effervescent mixture of citric acid and sodium bicarbonate formed the floating layer. The release layer contained captopril and various polymers such as HPMC-K15M, PVP-K30and Carbopol 934p, alone or in combination with the drug. The floating lag time was 10 min and the tablet remained floatable throughout all studies12.
ENCLOSURE-III
Objectives of the study The present research investigation is planned with the following objectives:

To perform preformulation studies.
To formulate physically and chemically stable floating matrix tablets of Curcumin.
To perform pre and post compression evaluation studies of the tablets.
To evaluate the formulations with respect to content uniformity, floating capacity, water uptake study, in vitro dissolution study etc.
The fit the release data into different kinetic models

MATERIALS AND METHODS
Materials:
DRUG : Curcumin
POLYMERS: Guar gum, Tween 20, β-chitin etc.
EXCIEPIENTS REQUIRED: PVP K30 etc.
Methods:
Direct compression, wet granulation any suitable or developed methods.
EVALUATION:
Pre compression parameters:

Angle of repose
Bulk density
Tapped density

Post compression parameters:

Weight variation
Hardness
Friability
Drug content estimation
In-vitro drug release
Drug-polymer interaction

Floating lag time
ENCLOSURE-IV
7.1. Source Of Data
The preliminary data required for the experimental study was obtained from:
a)Library: Sarada Vilas College of pharmacy, Mysore.
b)E-Library: Sarada Vilas College of pharmacy, Mysore.
c)Research publications.
d)Indian pharmacopoeia.
e) direct.com.
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:

Preformulation studies such as, solubility, compatibility of drugs with other excipients (IR, DSC, XRD), λmax, calibration, etc.

Prepared granules for floating tablets will be evaluated for:

a)Angle of repose
b)Drug content uniformity
c)Bulk density
d)Tapped density

Prepared floating tablets will be evaluated for:

a)Hardness
b)Thickness & diameter
c)Weight variation test
d)Friability test
e)In vitro Buoyancy studies
f)In vitro dissolution time
g)Release kinetics
Characterization:-
Characterization of floating matrix tablet compatability study by FTIR and in vitro release study, solid state by DSC.
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 briefl
No
7.4 Has ethical clearance been obtained from your institute in case of 7.3?
NOT APPLICABALE
ENCLOSURE-VII
LIST OF REFERENCES
1)Yichun S, Yingxu P, Yixin C, Atul JS. Application of artificial neural networks in the design of controlled release drug delivery systems. Adv. Drug Dev. Rev 2003;55:1201-1215
2)Preetha anand, Ajaikumar B. Kunnumakkara, Robert A. Newman, and Bharat B. Aggarwal. Bioavailability of curcumin: problems and promises. Mol Pharmaceutics 2007;4(6); 807-818.
3)AroraShweta, Ali Javed, AhujaAlka, KharRoop K. and BabootaSanjula. Floating Drug Delivery System: A review. AAPS Pharm SciTech. 2005; 06(03): E372-E390.
4) Xiao QiangXu, Minije Sun, FengZhi, Yiqiao Hu. Floating matrix dosage form for phenoporlamine HCL based on gas forming agent: In vitro and in vivo evaluation in healthy volunteers. Int J Pharm. 2006; 310:139-145.
5)Amit P, Kumar JS, Harishanker P, Tarkeshwar S, Arpit S. Formulation Development and Evaluation of Famotidine Floating Tablet. Int J Pharm Sci. 2010;4(3):224-9.
6)Panigrahy RN, Mahale AM, Dhaked PS. Formulation and invitro evaluation of combined floating mucoadhesive tablet of metoprolol succinate. Int J Pharm Sci. 2011; 3(2): 221-6.
7)Sharma S, Sharma A, Jha KK. The study of Captopril floating matrix tablets using different polymers as release retarding agent. The Pharma Research. 2009; 01:34-40.
8)Gupta SK, Gupta U, Omray LK,Yadav R, Soni VK. Preparation and characterization of floating drug delivery system of Acyclovir. International Journal of Applied Pharmaceutics. 2010; 2(3): 7-10.
9) Ramesh B, Rongala ASN, Madhusudan RY, Kishan V. Development and evaluation of gastroretentive norfloxacin floating tablets.Acta Pharm 2009;59:211–21.
10) Raghavendra RNG,Pentewar R, Thube k, Suryakar VB. Formulation and in vitro evaluation of gastric oral floating tablets of cefixime for controlled release. Res J Pharm Biol Chem Sci 2010;1(3):141-54
11)Jaimini M, Rana A.C, Tanwar Y.S. Formulation and Evaluation of Famotidine floating tablets. Current Drug delivery, 2007; 4:51-55.
12)Rahman Z, Ali M, Khar RK. Design and evaluation of bilayer floating tablets ofcaptopril. Acta Pharm.2006; 56:49-57.