PREPARATION AND EVALUATION OF ACECLOFENAC

SOLID DISPERSIONS AND ITS TABLETS

DISSERTATION PROTOCOL

Submitted to the

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA

BY

ABHAY KUMAR SINGH
DEPARTMENT OF PHARMACEUTICS

UNDER THE GUIDANCE OF

Dr. SUNIL KUMAR AGARWAL Phd

PROFESSOR

DEPARTMENT OF PHARMACEUTICS

Priyadarshini College of Pharmacy,

Koratagere Tumkur-572129

2012-13.

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) /

ABHAY KUMAR SINGH

M. PHARM, PART-I DEPARTMENT OF PHARMACEUTICS PRIYADARSHINI COLLEGE OF PHARMACY. KORATAGERE TUMKUR-572129 , KARNATAKA
2 / Name of the Institution / PRIYADARSHINI COLLEGE OF PHARMACY. KORATAGERE TUMKUR-572129 , KARNATAKA
3 / Course of the Study and Subject /

Master of Pharmacy in Pharmaceutics

4 / Date of Admission to the Course /
26-07-2012
5 /

Title of the Topic

/ “PREPARATION AND EVALUATION OF ACECLOFENAC SOLID DISPERSIONS AND ITS TABLETS”
YNTESIS

6  BRIEF RESUME OF THE INTENDED WORK

6.1  NEED FOR THE STUDY

Bioavailability is the most important property of a dosage form, among various factors that affect the bioavailability, it has been recognized with certainty that dissolution behavior and the factors affecting such performance are of paramount importance in the design and evaluation of solid dispersion the pharmaceutical technology is by far the most important and the most advancing field of pharmaceutical research. With the recent advent of combinatorial chemistry and high through put screening of potentially therapeutic agents the number of poorly soluble drug candidates has risen sharply and the formulation of these compounds for oral delivery now presents one of the most frequent and greatest challenges to the Pharmaceutical Technologies.

Among the various approaches to enhance the dissolution rate of poorly water-soluble drugs, preparation of solid dispersion systems often proved to be successful with number of drugs. This system provides the possibility of reducing the particle size of drugs to nearly a molecular level, to transform the drug from the crystalline form to the partial amorphous state and/ or to locally increase the saturation solubility.

In the present investigation, an attempt has been made to improve the dissolution rate of ACECLOFENAC through the preparation of solid dispersions using PEG 6000, Mannitol, Sodium Carboxy Methyl Cellulose, Poly Vinyl Pyrolidine, etc. as carriers, with different techniques of preparation like Physical Mixing Method, Solvent Evaporation Method, and Kneading Method.

The prepared dispersions may be evaluated for their physico-chemical and dissolution characters, the best-selected solid dispersions may be performed.

6.2.  REVIEW OF LITERATURE

1.  Chitra k1etal (2003). Studied the influence of solubility of Rofecoxib released from the solid dispersion system using different water-soluble carriers like Urea, Mannitol, PEG 6000, and PVP by common solvent method and melting method.

2.  Gupta MK2 Bonger R H, Goldman D (2002): reported the mechanism for further enhancement in drug dissolution from solid dispersion granules upon storage. Two proton –donating drugs Bay 129566. Naproxen and a non-proton donating drugs were studied; Granules containing progesterone (a non-proton donating drug) do not show an increase in the amount of drug hydrogen bonded to Neusilin upon storage.

3.  Vippagunta SR3 Maul Ka, Tallavaibala S, Grant DJ (2002): conclude the method of preparation of solid-state characterization of Nifedepine solid dispersion. The results indicate that the Nifedepine solid dispersion is physically stable over 8 weeks. Also indicate that Nifedepine is released faster from the solid dispersion than from the pure crystalline drug of the same particle size.

4.  Lifa4 HU J H, Wang H (2002): studied the dissolution improvement of poorly soluble SILY from solid dispersion of PEG 6000 can be illuminated by the changes of the lattice parameters of PEG 6000 on drug.

5.  P S Sona5etal (2004), Studied the solid dispersion of Rofecoxib in PEG’s by solvent evaporation method using chloroform as the solvent, they reported that the dissolution rate followed first order kinetics, as the concentration of polymer was increased the dissolution rate was increased.

6.3.  MAIN OBJECTIVES OF THE STUDY

In this investigation we propose

  1. Literature survey on solid dispersions, methods and carriers for solid dispersions
  2. Preparation of Calibration Curve for the estimation of “ACECLOFENAC”
  3. To evaluate Physical Properties like Hardness, Friability, Density etc.

Preparation of Solid Dispersions of ACECLOFENAC by any suitable methods like,

·  Physical Mixing Method6

·  Solvent Evaporation Method

·  Kneading Method

Using PEG 6000, Mannitol, Sodium CMC, PVP, etc. as carriers.

  1. Evaluation:

·  Drug Content Uniformity

·  To perform in-vitro dissolution studies

  1. Drug-carrier interaction studies by

§  Differential Scanning Colorimetry

§  FT-Infrared Spectroscopy

  1. Formulation of Aceclofenac tablets containing solid dispersions of Aceclofenac and their in-vitro dissolution studies.

7.  To evaluate the stability studies of a formulation as per ICH guidelines.

7. MATERIALS AND METHODS:

7.1  SOURCE OF DATA

The preliminary data required for the experimental study is obtained from-

  1. CD-Rom search available at National Center for Scientific Information (NCSI), Indian institute of Sciences, Bangalore, Dr. H.L.T. College of Pharmacy Library, Scientific abstracts, Journals, Internet sources and Relevant Books.
  2. The data will be collected by Laboratory investigation and will be recorded.

7.2.  METHODS OF COLLECTION OF DATA

  1. The various powder characteristics like bulk density, angle of repose, Carr’s index, dispersability etc, will be evaluated.
  2. Solid dispersions shall be prepared by using various carriers. The effect of these carriers and their ratios on drug release shall be studied.
  3. Tablet shall be compressed on 10 Rotary Tablet Compression Machine (RIMEK INDIA, Ahmedabad).
  4. The analytical method for the drug shall be developed and validated using UV-Spectrophotometer (UV-1700 SHIMADZU, JAPAN). The formulation shall be evaluated for the pre-compression and post compression characteristics.
  5. In-vitro dissolution studies shall be carried out in the USP Dissolution apparatus (DISSO 2000, LAB INDIA). The data will be subjected to statistical analysis and mechanism and kinetics of release shall be studied and reported.
  6. The stability study at various temperatures shall also be conducted.

7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so please describe briefly

NO

8.  LIST OF REFERENCES:

1.  Chitra.K, Sujatha.K, Arivaraasu, Vasantha.J, Studied on Rofecoxib solid dispersions, The Antiseptic, 2003; 100(8): 308-310.

2.  Gupta.M.K, Bonger.R.H, Goldman.D, Mechanism for further enhancement in drug dissolution from solid dispersion granules upon storage. Pharm.Dev.Techno, 2002(7): 103-112.

3.  Vippagunta.S.R, Maul.KA, Tallavaibala.S, Grant.D.J, solid-state characterization of Nifedepine solid dispersion. Int.J.Pharm.Sci, 2002 (236): 111-123.

4.  Lifa, HU J.H., Wang.H, Relatives between lattice changes and the function of dissolution improvement of poorly soluble drug silymarin based upon PEG 6000 solid dispersion system of PEG 6000. Yaoxue Xue Bao, 2002 (37): 294-298.

5.  P.S.Sona, Gopal Rao, P.Sudhakar Reddy, T.K.Ravi. Studied the solid dispersion of Rofecoxib in PEG’s - an approach to enhance the solubility and dissolution rate, Pharmainfonet.net, 2004.

6.  James L Ford, The current status of solid dispersions, Parma Acta Helv 1986, 61 (3): 69-88.

7.  Patel MM, Patel DM, Fast dissolving valdecoxib tablets containing solid dispersion of Valdecoxib, Ind. J. Pharm. Sci, 2006,68(2): 222-226.

8.  Toshio Ohara, Satoshi Kitamura, Teruyuki Kitagawa and Katsuhide Terada,
Dissolution mechanism of poorly water-soluble drug from extended release solid dispersion system with ethyl cellulose and hydroxypropylmethylcellulose Int. J Phar.Sci, 2005 sep, 302(1-2): 95-102.

9.  Sweetman SC.Martindale The Complete Drug Reference. 34th ed, Pharmaceutical Press, London 2005: 11-12.

10.  Kishore Kumar.N, Mural Mohan Babu.G.V, Himasankar.K. Comparative studies on effect of some hydrophilic polymers on dissolution rate of poorly water-soluble drug meloxicam, Indian Drugs, 2002; 39(6): 323-329.

11.  Raymond C. Rowe, Paul J. Sheskey and Paul J. Weller, 4th ed, Handbook of Pharmaceutical Excipients, The pharmaceutical press, London, 2003: 97,373,469 , 508.

9 / Signature of the candidate
10 / Remarks of the Guide / Topic selected for Dissertation work is satisfactory. This can be carried out in our Laboratory.
11 / Name and Designation of
(In Block Letters)
11.1  Guide
11.2  Signature / Dr. SUNIL KUMAR AGARWAL Phd
PROFESSOR
DEPARTMENT OF PHARMACEUTICS
PRIYADARSHINI COLLEGE OF PHARMACY,
KORATAGERE, TUMKUR-572129,
KARANATAKA.
11.3  Co – Guide
(If any)
11.4  Signature
11.5  Head of the Department
11.6  Signature / Dr. SUNIL KUMAR AGARWAL Phd
PROFESSOR
DEPARTMENT OF PHARMACEUTICS
PRIYADARSHINI COLLEGE OF PHARMACY,
KORATAGERE, TUMKUR-572129,
KARANATAKA.
.
12 / 12.1  Remarks of the Chairman and Principal
12.2  Signature

.

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