DEVELOPMENT AND EVALUATION CO-PROCESSED EXCIPIENTS FOR SUSTAIN DRUG DILIVERY OF LORNOXICAM M. Pharm Dissertation Protocol
Submitted
Rajiv Gandhi University Of Health Sciences, BANGALORE, karnataka
By
adhik.r.vyawahare
B. Pharm.
Under the guidance of
AEJAZ AHMED
m.pharm., (Ph.d.)
Asst. Professor
Dept. of Pharmaceutics,
Luqman College of Pharmacy, Gulbarga
DEPARTMENT OF pharmaceutical technology
LUQMAN COLLEGE OF PHARMACY,
GULBARGA – 585102
2012-2013
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA
BANGALORE
ANNEXURE - II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
Name of the Candidate (In block letters) Permanent Address / ADHIKRAO RANGNATH VYAWAHAREAT MALWADI NO 1 TA INDAPUR DIST PUNE 413106
MAHARASHTRA.
Name of the Institution / LUQMAN COLLEGE OF PHARMACY,
GULBARGA-585 105.
Course of Study and Subject / M.PHARM.
(PHARMACEUTICAL TECHNOLOGY)
Date of Admission to Course / 14-07-2012
Title of the Topic / CO-PROCESSED EXCIPIENTS FOR SUSTAIN DRUG DILIVERY OF LORNOXICAM
Brief resume of the intended work
Need for the study:Now a day’s tablets have more than 80% of all dosage forms administered to human being The principal reasons for their continued popularity include their ease of manufacture, their convenience of dosing, and their stability compared with liquid and semi-solid presentations. There are different mode of tablet manufacture Direct compression, Wet granulation and Dry granulation. Direct compression of the active ingredient with other appropriate excipients to form a tablet, normally for medium- to high-potency compounds where the drug content is less than 30% of the formulation. The advantages of direct compression are well-known, the most important being fewer processing stages and the elimination of heat and moisture effects. Co-processing is another way that new excipients are coming to market without undergoing the rigorous safety testing of a completely new chemical1. That is, excipients that have been combined together in a synergistic manner and which are more beneficial than simple physical admixtures, such as silicified microcrystalline cellulose2. OR It can be defined as combining two or more established excipients by an appropriate process .Co processing of excipients could lead to the formation of excipients with superior properties compared to the simple physical mixtures of their components. The main aim of coprocessing is to obtain a product with added value related to the ratio of its functionality/price3, 4. Also in the preparation of tablet, major time is required for the step of granulation but by using co-processed excipients one can get directly compressible powder that eliminate the step of granulation .Challenge for tablets and capsule manufacturing comes from the flow properties of the materials to be compressed. Most of the formulations contain excipients at higher concentration than active drug. Hence by using this approach we can increases the flow properties of compressible material and also reduce concentration of excipients used.
Lornoxicam is non –steriodal anti inflammatory drug with Analgesis property belong to the class of oxicams,the mode of action is partly based on relaese of prostaglandin synthesis used for the treatment of various types of pain, especially resulting from inflammatory diseases of the joints, osteoarthritis, surgery, sciatica, and other inflammations.
Lornoxicam is absorbed rapidly and almost completely from the gastro-intestinal tract. Maximum plasma concentrations are achieved after approximately 1 to 2 hours. Food protracts the average time to maximum concentration from 1.5 to about 2.3 hours Therefore, in the present study an attempt will be made development and evaluation of Lornoxicam matrix tablets as sustain release delivery system with a view to enhance its bioavailability, duration of action and convenience of administration (reduced dosing frequency) leading to improved patient compliance.5
6.2 Review of Literature
Literature survey was carried out on the proposed research work by referring various Scientific Research Journals, Internet facilities and science direct.
1. T.D.Cabelka et al designed Direct Compression of Sustained-Release Hydrophilic Matrix Containing
HPMC and MCC Part II: Effects of Silicified MCC Grades and a Glidant on Powder Flow and use a direct
Compression method for bioactive Sustained-Release.6
2. Madhusmruti et al, Development of Propranolol hydrochloride matrix tablets: an investigation on effects
of combination of hydrophilic and hydrophobic matrix formers using multiple comparison analysis. 7
3. Rakesh P. Patel, Mansi Bhavsar1 , Ashok H. Baria et al Study the Effect of Co-Processing Method and
Different Process Variables on the Meclizine HCL Fast Dissolving.8
4. Crowley reported that the release rate of guaifenesin from ethyl cellulose matrix tablets prepared by direct
compression was dependent on the ethyl cellulose particle size, and compaction force . 9
5. Ishikawa et al. reported novel microcrystalline cellulose (PH-M Series) for preparation of rapidly
disintegrating tablet using by direct compression. Study demonstrated that the acetaminophen or
ascorbic acid tablets containing novel microcrystalline cellulose (PH-M Series; particle size, 7 - 32
micron) has decreased sensation of roughness and rapidly disintegrated by saliva when taken orally
compared to conventional Avicel PH-102 10
6. Kothari et al compared the powder and mechanical properties of different batches of low crystallinity
powdered cellulose (LCPC) with those of different grades of Avicel, Emcocel, Solka Floc BW-40 and
Solka Floc BW-100 and concluded that the LCPC materials reported by them have powder properties that
are quite different from the microcrystalline cellulose and powdered cellulose and can be recommended
as a potential direct compression excipients11
7. J. Ayyappan, P.Umapathi et al, Development and Evaluation of a Directly Compressible Co-processed
Multifunction Sustained Release Agent for Gliclazide Sustained Release Tablets12
Madishetty, Vamshi Krishna et al The formulation of pseudoephedrine Hydrochloride (extended release
was prepared by using different polymers (HPMC and ethocel) and with different diluents (dibasic
calcium phosphate anhydrous, dibasic calcium phosphate dihydrate, lactose anhydrous and DCL-15) 13
8. Chitta Suresh Kumar, Kishore Kumar Reddy-Budideti et al, They developed sustained release matrix tablets of
Gliclazide using fruit mucilage from the plant Ficus glomerata. Varying ratios of drug and polymer viz. 1:0.25,
1:0.5, 1:0.75, 1:1.0 and 1:1.25 were selected for the study. From the dissolution study, it was concluded that dried
Ficus glomerata mucilage can be used as an excipient for making sustained release matrix tablets. 14
6.3 Objectives of the Study
The objective of the present work is to develop sustain release matrix tablets of Lornoxicam using co-
prossesed excipients
1. Selection of right process for development of sustain relase matrix tabletsusing co prossesed excipients. A process like wet grannulation method/direct compression etc is flexible and scalable.
2. Selection of co prossesed polymers to achieve sustained release for the required period of time.
3. The characterization of lornoxicam sustain release matrix tablets in terms of weight
uniformity,friability,content uniformity,hardness,in-vitro drug release etc.
7. / MATERIAL AND METHODS
7.1 / Materials
Drugs : Lornoxicam
Polymers : Ethyl Cellulose, HPMC, Eudragit S100, Polyvinyl Vinyl alcohol
Chemical : Dichloromethane, Ethanol, Polyvinyl acetate, Acetone, Liquid
paraffin, Calcium chloride, Isopropyl alcohol etc.
All other chemicals & reagents used will be of analytical grades.
Equipments :
1. UV/ Visible spectrophotometer (1700 Shimadzu)
2. Digital cover head stirrer
3. Electronic balance (Shimadzu Corporation BL-22H, Pune)
4. Thermostatic Hot Plate with Magnetic Stirrer (Remi Motor Mumbai)
5. Electrolab dissolution apparatus (USPXXIII)
6. Scanning electron microscopy.
7. Infrared spectrophotometer
7.2 / Method
1. Lornoxicam sustain release matrix tablet will be developed using co-prossesed excipients wet granulation or direct compression method, by use of various co-prossesed polymer such as Ethylcellulose and different grades of Eudragit polymer.
2. Determination Lornoxicam of by UV/visible spectrophotometric method.Evaluation of sustain relase matrix tablets.
A) Evaluation of Prepared Directly Compressible granules: Flow properties,Angle of
repose,Carr’s index,Hausner’s ratio,Bulkdensity,Tapped density,Moisture, Drug-polymer
interaction, Stability Studies.
B) Evaluation of tablet prepared by wet granulation for tablet Thickness, Size, Weight variation,Hardness test,Friability test, Drug content,Uniformity of Weight, In vitro dissolution testing, Drug-polymer interaction, Stability Studies, Based on the preliminary study of Drug and Polymer, suitable method will be optimized and utilized.
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 plan of work
7.4 / Has ethical clearance been obtained from your institution in case of 7.3?
Not applicable.
8. / List of References :
1. Rakesh P. Patel, Mansi Bhavsar1 , Ashok H. Baria. To Study the Effect of Co-Processing Method and Different Process Variables on the Meclizine HCL Fast Dissolving Tablet, International Journal of Pharmaceutical Research ,Volume 2, Issue 1, January-March 2010, 36-45.
2. Mira Jivraj, Luigi G. Martini and Carol M. Thomson. An overview of the different excipients useful for the direct compression of tablets, PSTT, Vol. 3, No. 2 February 2000,58-63.
3. Minakshi Marwaha, Deepak Sandhu, Rakesh Kumar Marwaha.Coprocessing of excipients: a review on excipient development for improved tabletting performance, International Journal of Applied Pharmaceutics; Vol 2, Issue 3, 2010, 41-47.
4. Rakesh P. Patel, Directly Compressible Materials via Co-Processing; International Journal of Pharmaceutical Tech Research; July-Sept 2009; Vol.1, No.3, pp 745-753.
5. Parikh BA et al “Formulation and evaluation of Lenoxicam fast dissolving tablets”, International journal of pharmacy,vol 2(4),2011,130-133.
6. T. D. Cabelka. Direct Compression of Sustained-Release Hydrophilic Matrix Tablets Containing HPMC and MCC Part II: Effects of Silicified MCC Grades and a Glidant on Powder Flow, The Dow Chemical Company, Larkin Laboratory, Midland, MI 48674 USA, Presented at the 27th International Symposium on Controlled Release of Bioactive Materials Paris, France, July -2000.
7. M. C. Gohel. A review of co-processed directly compressible excipients, Journal of Pharmaceutical Science; 2005; 8(1):76-93.
8. Rakesh P. Patel. Directly Compressible Materials via Co-Processing; International Journal of Pharmaceutical Tech Research; July-Sept 2009; Vol.1, No.3, pp 745-753.
9. Syed Namath Ulla, Anup Kumar Roy, Martand Kulkarni, Vinod Kumar SM. Formulation and Evaluation Of Sustained Release Matrix Tablets of Lornoxicam; International Journal of Drug Development & Research; Jan-March 2011, Vol. 3 Issue 1, 31- 44.
10. Ayyappan. J., Umapathi. P , Darlin Quine. Development and evaluation of a directly compressible co processed Multifunction sustained release agent for tablets, International Journal of Pharmacy and Pharmaceutical Sciences, Vol 2, Suppl 4, 2010, 201-205.
11. Madhusmruti Khandai, Santanu Chakraborty, Anuradha Sharma, Debashisha Panda, Nazia Khanam, Santosh Kumar Panda. Development of Propranolol hydrochloride matrix tablets: an investigation on effects of combination of hydrophilic and hydrophobic matrix formers using multiple comparison analysis; International Journal of Pharmaceutical Sciences Review and Research; Volume 1, Issue 2, March – April 2010, Article 001, 1-7.
12. Iyad Rashid, Mayyas Al-Remawia,c, Stephen A. Leharneb, Babur Z. Chowdhryb, Adnan Badwana. A novel multifunctional pharmaceutical excipient: Modification of the Permeability of starch by processing with magnesium silicate, International Journal of Pharmaceutics; 2011, 18–26.
13. Muhammad Akram, Syed Baqir Shyum Naqvi, Shahnaz Gauhar .Development of coprocessed micro granules for direct compression;, International Journal of Pharmacy and Pharmaceutical Sciences, Vol 3, Suppl 2, 2011, 64-69.
14. J. Ayyappan, P.Umapathi , Darlin Quine. Development and Evaluation of a Directly Compressible Co-processed Multifunction Sustained Release Agent for Gliclazide Sustained Release Tablets, Journal of Pharmaceutical Science and Research ,Vol.2 (7), 2010, 394-400.
9. / Signature of Candidate / (AHIKRAO.R.VYAWAHARE)
10. / Remarks of the Guide / Sustain Release Matrix Tablet Of Lornoxicam Prepared Using co-Processed Ingredients will be useful for obtaining sufficient bioavailability of long time & effective plasma level can be achived.Hence recommended for registration
11. / Name & Designation of (in block letters)
11.1 Guide / MR. AEJAZ AHMED
M.pharm (Ph,D)
ASST. PROFESSOR,
LUQMAN COLLEGE OF PHARMACY, GULBARGA.
11.2 Signature
11.3 Co-guide
11.4 Signature
12. / 12.1 Remarks of the Principal
12.2 Signature