RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA
BANGALORE
ANNEXURE – II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / Name of the Candidate & Address (in block letters) / : / ASHOKGOUD N.PATILAt Post: Algood, Tq: Basavakalyan,
Dist: Bidar, Karnataka – 585 419
2. / Name of the Institution / : / H.K.E. SOCIETY’S COLLEGE OF PHARMACY,
SEDAM ROAD, GULBARGA-585 105
3. / Course of Study and Subject / : / M.PHARM(PHARMACEUTICAL TECHNOLOGY)
4. / Date of Admission to Course / : / 31st May, 2007
5. / Title of the Topic / : / DEVELOPMENT AND EVALUATION OF LOW COST DIRECTLY COMPRESSIBLE EXCIPIENTS FOR PIROXICAM DISPERSIBLE TABLETS
6. / Brief resume of the intended work
6.1 Need for the study:
The choice of excipients in a tablet formulation depends on the active ingredient (drug), the type of tablet, the desired characteristics and the manufacturing process used. Over past four decades, improvements in the availability of excipients with consistent physical properties (including particle size and shape, and improved functionality such as compaction and flow), have revolutionized tablet production on a commercial scale1.
Direct compression technology is receiving increasing interest due to the savings in equipments, materials, labour, time and energy coupled with other advantages such as improved drug stability due to elimination of heat and moisture, over conventional granulation technique. However most of the directly compressible excipients currently available in the market are imported and hence have prohibitive cost2.
Hence, the aim of the present study is to develop low cost directly compressible granular excipients based on various sugars / polyols such as mannitol, sorbitol, erythritol, xytitol and maltodextrin along with a small percentage of starch, which can be used in the design of dispersible or mouth dissolving tablets (orodispersible tablets) using piroxicam (analgesic, anti-inflammatory and anti-pyretic) as a model drug3,4.
6.2 Review of Literature:
Literature review shows very few published reports on the development of low cost directly compressible excipients suitable for direct compression of dispersible / orodispersible tablets, with a majority of the reports being that of co-processed lactose-starch. The following are some of the published works on directly compressible granular excipients.
Ø An investigation of direct compression characteristics of co-processed lactose-starch using factorial design was reported by Gohel MC and Jogani PD2. A 32 full factorial design was employed to study the effect of lactose / starch ratio and the percent starch paste. Starch paste was prepared by heating the aqueous dispersion of starch at 80ºC for 15 min. The paste was used to prepare granules. Then tablets were prepared on a single stroke tablet machine. The % fines, Carr’s index, granular friability, crushing strength and % friability were selected as the dependent variables. A product consisting of lactose / starch ratio 71:29 exhibited excellent functionality and good tableting characteristics.
Ø Matthew J et al5 reported effects of lubrication on the compaction and post compaction properties of directly compressible maltodextrins. In this study the effects of various concentrations of magnesium stearate as a tablet lubricant on three types of maltodextrins were investigated. The maltodextrins were physically processed by the methods of spray drying, fluidized bed agglomeration and roller compaction were compared for their compaction and post-compaction properties.
Ø Recent advances in sugar-based excipients has been reviewed by Bowe KE6. The author illustrates some recent advances with recent case studies of tests on two new excipients, crystalline maltose and directly compressible sucrose (containing sorbitol).
Ø Evaluation of two dextrose-based directly compressible excipients (Emdex and Maltrin M510) was reported by Olmo IG and Ghaly ES7. Compacts prepared from Maltrin M510 had a longer disintegration time and slower drug release than compacts of the same composition but prepared with Emdex.
Ø The consolidation and compressibility properties of some novel directly compressible filler-binders (viz., Ludipress, Cellactose 80, Tablettose 70 and Tablettose 80) was reported8. The dilution potentials of the above excipients was also determined after dilution with Spherolac 100 (a coarse sieved hydrous crystalline lactose).
Ø A comparative study of modified starches in direct compression of a poorly water soluble drug (hydrochlorothiazide) has been reported by Okafor IS et al9. The starches were obtained locally from common plant sources and were modified through physicochemical treatment. Each modified starch was used as the only filler-binder-disintegrant in the formulation of hydrochlorothiazide tablets containing 25 mg of the drug. The tablets were produced by the direct compression technology. Sta-Rx 1500, a directly compressible starch, was used as basis for comparison.
Ø An invention relating directly compressible starch as enhancer of properties of excipient when mixed with one more different excipient was patented by Jacques Loic et al10. The present invention relates to a mixture of a starch and atleast one other excipient for tableting wherein the starch is free-flowing compressible processed starch powder suitable for use both as a binder and as a disintegrant in tablets. The free flowing starch powder improves the characteristics and the properties of the tablets when mixed with one or more different excipients.
Ø Zhang Y et al11 reported physical properties and compact analysis of commonly used direct compression binders / fillers. The basic physicochemical property and binding functionality of commonly used commercial direct compression binders / fillers were studied. The compressibility of these materials was also analysed using compression parameters derived from the Heckel, Kawakita and Cooper-Eaton equations.
Ø Spherical composite particles of rice-starch and microcrystalline cellulose as a new co-processed excipient for direct compression was reported by Limwong V et al12. In this investigation, composite particles of rice-starch (RS) and microcrystalline cellulose were fabricated by spray drying technique to be used as a directly compressible excipient.
Ø Avachat Amelia and Ahire VJ13 worked on the characterization and evaluation of spray dried co-processed excipients and their application in solid dosage forms. The work which evaluates and characterizes two spray dried co-processed materials, one comprising of microcrystalline cellulose, colloidal silicon dioxide and sodium starch glycollate and the other composed of microcrystalline cellulose, colloidal silicon dioxide and cross povidone. This study revealed that the co-processed materials have excellent flow properties, high compressibility, render low disintegration time to tablets and have better binding properties.
Ø Development of directly compressible powders via co-spray drying has been reported by Gonnissen Y et al14. In this work, continuous production of directly compressible powders was achieved by coprocessing acetaminophen and carbohydrates (viz., erythritol, lactose, maltodextrin and mannitol) via spray drying and evaluated on spray drying processibility, powder hygroscoicity, flowability and compactibility. A combination of erythritol, maltodextrin and mannitol was selected for further formulation and process optimisation of co-spray dried powders for direct compression.
6.3 Objectives of the study:
In the present work, studies will be carried out on the development and evaluation of low cost directly compressible excipients for dispersible tablets using piroxicam as a model drug.
The developed excipients will be evaluated for % fines, hygroscopicity, granule strength, flow properties and compressibility index (Carr’s index).
The designed tablet formulations will be evaluated for hardness, friability, weight variation, dispersion time (including wetting time and water absorption ratio), drug content, in-vitro dissolution rate (in pH 6.8 phosphate buffer), short-term stability and drug-excipient interaction (IR spectroscopy).
Methods for the Preparation of Dispersible / Mouth-dissolving tablets:
The dispersible / mouth-dissolving tablets of piroxicam will be prepared by direct compression method using any of the methods described below:
a) Disintegrant Addition: In this method, super-disintegrants such as sodium starch glycolate, cross-linked PVP etc. will be included to obtain faster disintegration.
b) Effervescent Technique: In this method, a mixture of sodium bicarbonate and anhydrous citric acid is included in order to further enhance disintegration and taste masking effect.
7. / MATERIALS AND METHODS:
7.1 Sources of data:
a) Internet
b) Gulbarga University Library, Gulbarga.
c) I.I.C.T. Library, Hyderabad
d) International Pharmaceutical Abstracts.
7.2 Method of Collection of Data:
The developed directly compressible excipients will be evaluated for % fines, hygroscopicity, granule strength, flow properties and compressibility index. The designed dispersible / mouth-dissolving tablet formulations of piroxicam will be evaluated for hardness, firability, weight variation, dispersion time (including wetting time and water absorption ratio), drug content, in-vitro dissolution rate (in pH 6.8 phosphate buffer), short-term stability and drug-excipient interaction.
a) Estimation of Drug Content: The drug content of mouth-dissolving tablets will be determined spectrophotometrically on the filtered methanolic extracts of the drug.
b) Disintegration Time: Disintegration time of the mouth-dissolving tablets will be determined by using distilled water at 37±2ºC as the medium using tablet disintegration test apparatus BP.
c) In vitro dissolution Study: In vitro drug release study of the prepared mouth-dissolving tablets will be carried out in 900 ml of pH 6.8 phosphate buffer in USP XXIII Tablet Dissolution Tester (Electrolab, TDT-06N) using paddle stirrer at 50 rpm.
d) Short-term Stability: The promising mouth-dissolving tablets of the drug will be stored at a temperature of 40±2ºC with 75±5% relative humidity for 6 weeks and evaluated for drug content, disintegration time and drug-excipient interactions (IR spectroscopy).
7.3 Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so, please describe briefly.
------Not under the plan of our work ------
7.4 Has ethical clearance been obtained from your institution in case of 7.3.
------Not applicable ------
8. / LIST OF REFERENCES:
1. Zak T Chowhan. Tablet Ingredients (Section-4). www.fmc.com.
2. Gohel MC and Jogani PD. An investigation of direct compression characteristics of co-processed lactose-starch using factorial design. Indian J. Pharm. Sci.,2003; 65(1): 31-8.
3. Martindale: The complete Drug Reference, Thirty-third edn., Pharmaceutical Press, London; 2002: 79-80.
4. The Indian Pharmacopoea: Controller of Publications, Ministry of Health and Family Welfare, Govt. of India, 4th edn., New Delhi; 1996: 600-01.
5. Mollan MJ (Jr.) Metin Celik. The effects of lubrication on the compaction and post-compaction properties of directly compressible maltodextrins. Int. J. Pharm., 1996; 144(1): 1-9.
6. Kathleen E. Bowe. Recent advances in sugar based excipients. Pharm. Sci. Tech. Today, 1998; 1(4): 166-73.
7. Olmo IG, Ghaly ES. Evaluation of two dextrose based directly compressible excipients. Drug Dev. Ind. Pharm., 1998; 24(8): 771-78.
8. Gonul N, Ogan-Hascicek C, Bavkara T. The consolidation and compressibility properties of some novel directly compressible filler-binders. Acta. Pol. Pharm., 2000; 57(4): 311-17.
9. Okafor IS, Ofoefule SI, Udeala OK. A comparative study of modified starches in direct compression of a poorly water soluble drug (hydrochlorothiazide). Boll. Chim. Farm., 2001; 140(1): 36-9.
10. Jacques Loic, Marie Michaud, Liesbeth Maria, Fernande Meeus. Directly compressible starch as enhancer of properties of excipients when mixed with one more different excipient. US Patent. 604299, 24 Sept. 2002.
11. Zhang Y, Law Y, Chakrabarti S. Physical properties and compact analysis of commonly used direct compression binders. AAPS PharmSciTech., 2003; 4(4): Article-62.
12. Limwong V, Sutanthavibul N, Kulvanich P. Spherical composite particles of rice-starch and microcrystalline cellulose: A new co-processed excipient for direct compression. AAPS PharmSciTech., 2004; 5(2): Article-30.
13. Avachat Amelia, Ahire VJ. Characterization and evaluation of spray dried co-processed excipients and their application in solid dosage forms. Indian J. Pharm. Sci., 2007; 69(1): 85-90.
14. Gonnissen Y, Remon JR, Vervaet C. Development of directly compressible powders via co-spray drying. Eur. J. Pharm. Biopharm., 2007; 67(1): 220-26.
9. / Signature of Candidate / [ASHOK GOUD PATIL]
10. / Remarks of the Guide / Newer low cost directly compressible excipients will be cost-effective in the design and development of dispersible and mouth dissolving tablets, with improved patient compliance and oral bioavailability.
11. / Name & Designation of (in block letters)
11.1 Guide / Dr. P.V. SWAMY
M.Pharm., Ph.D.
PROFESSOR
DEPT. OF PHARMACEUTICAL TECHNOLOGY
H.K.E.S’s COLLEGE OF PHARMACY, GULBARGA.
11.2 Signature
11.3 Co-Guide: / SIDRAMAPPA B. SHIRSAND
M.Pharm.
ASST. PROFESSOR
DEPT. OF PHARMACEUTICAL TECHNOLOGY
H.K.E.S’s COLLEGE OF PHARMACY, GULBARGA.
11.4 Signature
12. / 12.1 Remarks of the Chairman & Principal
12.2 Signature