DESIGN AND EVALUATION OF COLON SPECIFIC DRUG DELIVERY SYSTEM CONTAINING LORNOXICAM MICROSPONGES

M.PHARM DISSERTATION PROTOCOL

SUBMITTED TO THE

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES
BANGALORE,KARNATAKA.
BY
TODMOD SAMREEN SARDAR MEHRUNISSAB.Pharm
UNDER THE GUIDANCE OF
M.A.SALEEM M. Pharm.(Ph.D)

PG DEPARTMENT OF PHARMACEUTICS
LUQMANCOLLEGE OF PHARMACY
GULBARGA, KARNATAKA -585104
2013-14

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1 / NAME OF THECANDIDATE
ADDRESS
/ TODMOD SAMREEN SARDAR MEHRUNISSA
C/O LUQMANCOLLEGE OF PHARMACY, P.O BOX NO. 86, BEHIND P&T COLONY,
OLD JEWARGI ROAD,
GULBARGA 585102.
2 / NAMEOF THE INSTITUTE / LUQMANCOLLEGE OF PHARMACY
3 / COURSE OF THE STUDY / M. PHARM IN PHARMACEUTICS
4 / DATE OF ADMISSION / 11/06/2013
5 / TITLE OF THE TOPIC / “DESIGN AND EVALUATION OF COLON SPECIFIC DRUG DELIVERY SYSTEM CONTAINING LORNOXICAM MICROSPONGES”
6
7
8 / Enclosure-I
BRIEF RESUME OF INTENDED WORK:
6.1 Need for study
Now a days,various routes of administration have been explored for the effective deliveryof the drug. The oral route is considered to be most convenient for the administration of drugs to patients. Oral administration of conventional dosage forms drug normally dissolves in gastro-intestinal fluids and is absorbed from these regions of gastro-intestinal tract, which depends on the physico chemical properties of the drug. The serious drawback in conditions where localized delivery of the drugs in the colon is required or in the condition where a drug needs to be protected from the hostile environment of upper GIT1,2.
Targeted drug delivery into the colon is highly desirable for local treatment of variety of bowel diseases such as ulcerative colitis, cirrhosis disease,amoebiosis,colonic cancer, local treatment of colonic pathologies and systemic delivery of protein and peptide drugs3. Colon specific drug delivery system should be capable of protecting the drug in route to the colon i.e drug release and absorption should not occur in the stomach as well as in small intestine4.
Various pharmaceutical approaches which have been used for targeting drugs to the colon are mainly based on pH-dependent, time dependent, osmotic pressure and/or bacterial dependent systems5,6,7.
The formulation of microsponge drug delivery system has many advantages over other technologies like compatible with most vehicles and ingredients, stability over a pH range of 1-11, stable up to temperature 1300 C, have higher payload (50 to 60%), still free flowing and can be cost effective.Release can be controlled through diffusion or other triggers such as moisture, pH, friction, or temperature. Microsponge delivery system can be incorporated into conventional dosage forms such as creams, lotions, gels, ointments, and powder and share a broad package of benefits. The microsponges show several advantages such as uniform distribution at the target region and smaller risk of dose dumping8.
In rheumatoid arthritis, prolonged treatment of NSAIDs is required to minimize the joint damage and enhancing physical function of the body. Lornoxicam is one of the NSAIDs used in rheumatoid arthritis. Lornoxicam belongs to oxicam class with analgesic, anti-inflammatory properties. It is absorbed in GIT, bioavailability is 90-92% and it inhibits the prostaglandin synthesis. It is used in the musculoskeletal joint disorders and other painful conditions including postoperative pain. The conventional tablets make the drug immediately available for absorption in upper gastrointestinal tract resulting local GI toxicity varying from minor gastric discomfort to ulceration and bleeding of mucosa. GI toxicity not only caused by inhibition of prostaglandin synthesis, but is probably also due to direct contact of the drug with mucosa9. In addition, repeated daily dosing of 3 to 4 times is required in maintenance therapy that influences patient compliance.
To overcome these problems, the present study is plan to develop novel colon targeted drug delivery system containing Lornoxicam microsponge.
6.2 REVIEW OF THE LITERATURE:
Vikas Jain and Ranjit Singh10had worked on development and characterization of Eudragit RS 100 loaded microsponges and its colonic delivery using natural Polysaccharides. Paracetamol loaded Eudragit based microsponges were prepared using quasi emulsion solvent diffusion method with DCM as internal phase solvent. The colon specific formulations were prepared by compression coating of microsponges with pectin: hydroxypropyl methylcellulose (HPMC) mixture followed by tabletting. Prepared microsponges exhibited characteristics of an ideal delivery system for colon targeting. Further colon specific tablets based on microsponges could provide effective local action as microsponges may selectively be taken up by the macrophages present in colon.
Comoglu T., Gonul N and Baykara T11had prepared microsponges containing ketoprofen and Eudragit RS 100 by quasi emulsion solvent diffusion method. The effects of different mixing speeds, drug/polymer ratios, solvent/polymer ratios on the physical characteristics of the microsponges as well as the in vitro release rate of the drug from the microsponges were investigated. All the factors studied had an influence on the physical characteristics of the microsponges.
Mine Orlu, Erdal Cevher and Ahmet Araman12 had studied the design and evaluation of colon specific drug delivery system containing flurbiprofen microsponges. Microsponges containing flurbiprofen (FLB) and Eudragit RS 100 were prepared by quasi emulsion solvent diffusion method. The effects of drug: polymer ratio, inner phase solvent amount, stirring time and speed and stirrer type on the physical characteristics of microsponges were investigated. The thermal behaviour, surface morphology, particle size and pore structure of microsponges were examined. It was concluded that the microsponges can be used successfully in the systems designed for colon specific drug delivery. The results show that the microsponges were of spherical shape with spherical and cylindrical hole like pores. The plastic properties of microsponges allow direct compression of the microsponges to obtain mechanically strong tablets than the physical mixture of drug and polymer. The in vitro release profile shows that the drug release from the microsponges was faster, when compared to the rigid microparticles due to more porous internal structure of the microsponges.
Thiruganesh R, Uma Devi SK and Suresh S5has prepared pectin pellets of Aceclofenac for colon targeted drug delivery and coated the pectin pellets with pH dependent polymeric coating solution containing Eudrgit L 100 and S 100. The pellets were evaluated for physicochemical properties, drug content, dissolution, water uptake and erosion characteristics in-vitro drug release. Eudrgit coated pectin pellets prevented release of the Aceclofenac in the stomach and small intestine depending on the proportion of pectin used in the formulation. The in-vitro studies suggest that pectin pellets of Aceclofenac are promising for therapy of rheumatoid arthritis.
Manish Neekhra et al.,6has developed and evaluated colon targeted Ketorolac tromethamine capsule. The capsules were fabricated using combination of both microflora activated natural polysaccharide (guar gum) and pH dependent polymer (cellulose acetate phthalate). Guar gum was included in the formulations in various proportions such as 30% guar gum, 40% guar gum, 50% guar gum and 60% guar gum. They concluded that cellulose acetate phthalate coated capsules with 50% guar gum may be useful for drug targeted to the colon successfully.
Chickpetty SM and Raga Baswaraj13has designed to develop colon targeted compression coated delivery systems for Diclofenac sodium by using different proportions of guar gum(GG) and locust bean gum(LBG)mixture in the ratio 1:1 in combination with hydroxyl propyl methyl cellulose(HPMC) as a coating material. Different proportions of GG:LBG mixture:HPMC in the ratios 9:1,8:2,7:3,6:4 and 5:5 are formulated. They concluded that the ratio 6:4 released only 2.24% of drug in physiological environment of stomach and small intestine and released more than 90% of drug in colon.
Ghule prashant J, Karle Ganesh D and Saumya Das14has formulated and evaluated colon targeted drug delivery of Aceclofenac using guar gum and xanthan gum as carrier. In the present study, matrix and compression coated tablets of Aceclofenac containing different proportions of guar gum, xanthan gum such as (1.25:1.25),(1.5:1) and (1.75:0.75) were prepared. All formulations are evaluated for the hardness, friability, thickness, weight variation, drug content, uniformity and drug release studies.The results of the dissolution study showed that ratio of 1.75:0.75 is more likely to provide targeting of Aceclofenac for local action in the colon.
Rasika D Bhalke et al.,15 has developed colon targeted matrix tablets of Aceclofenac by using dextrin as a carrier and effective binder system of ethyl cellulose. Evaluation was done by different IPQC tests, content uniformity and in-vitro drug release study. They studied on different binders like ethyl cellulose, sodium CMC and sucrose in different proportions. They concluded that matrix tablet containing binder system of ethyl cellulose and dextrin as a carrier was found to be suitable for targeting the colon as compared to the other matrix tablets containing different binders.
Uma Devi SK, Thiruganesh R and Suresh S16has prepared chitosan tablets of Aceclofenac for colon targeted drug delivery and coated the tablets with pH dependent polymeric coating solution containing Eudragit L 100 and S 100. The tablets were evaluated for physicochemical properties, drug content, dissolution, water uptake and erosion characteristics in-vitro drug release. Eudrgit coated chitosan tablets prevented release of the Aceclofenac in the stomach and small intestine depending on the proportion of chitosan used in the formulation. The in-vitro studies suggest that chitosan tablets of Aceclofenac are promising for therapy of rheumatoid arthritis.
6.3. OBJECTIVES OF THE STUDY:
The important objectives of proposed research work are:
  1. To prepare a colon targeted formulation of Lornoxicam to prevent drug absorption from upper GIT, as this drug has pronounced GI irritation problem. Such a delivery system will reduce its side effects, decrease dose of drug, and improve its efficacy.
  2. To prepare microsponge using varying ratio of Lornoxicam and Eudragit RS 100 as to obtain the desired drug release profile.
  3. To formulate a colon targeting tablet by giving a compression coat of biodegradable polysaccharides i.e. Pectin & HPMC combination on core tablet of microsponge.
  4. To perform in-vitro drug release studies of core tablet of Lornoxicam microsponge and compression coated tablet of Lornoxicam.
ENCLOSURE: II
7.1 METHODOLOGY :
  1. Preformulation study for different standard tests.
  2. Preparation of microsponge by quasi-emulsion solvent diffusion method using different polymer concentration and optimization of various parameters.
  3. Characterization of microsponge by scanning electron microscopy, FTIR spectroscopy and DSC analysis.
  4. Evaluation of microsponge for production yield, actual drug content, entrapment efficiency, particle size analysis, flow properties and invitro dissolution study.
  5. Preparation and optimization of core tablet dosage form by direct compression method.
  6. Characterization of core tablet for postcompression parameters and invitro release study.
  7. Accelerated stability testing of core tablets as per ICH guidelines.
MATERIALS:
  1. Drug: -Lornoxicam
  2. Polymers: - Hydroxypropylmethylcellulose (HPMC K100M), Eudragit RS 100,Sodium carboxy methyl cellulose, Pectin, Polyvinyl alcohol, etc.
  3. Solvents: - Triethyl Citrate, Dichloromethane,
  4. Instruments: - Disintegration apparatus, Friability tester, Hardness tester, Dissolution apparatus, UV/visible Spectrophotometer, Ultrasonicator, Stability Chamber, Mechanical stirrer, Hot air oven, Vernier Caliper, etc.
7.2 SOURCE OF DATA:
1.All the National and International journals pertaining to medical and pharmaceutical sciences.
2. Library and e-library of Luqman College of Pharmacy, Gulbarga.
3. IndiaStudy.com
4. Drugs update.
5. RGUHS,Bangalore.
6. Indian Pharmacopoeia.
7.3 Does the study require any investigations or interventions to be conducted on patients or animals? If so, please describe briefly.
Not Applicable
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
Not Applicable
ENCLOSURE- III
REFERENCE:
  1. Poonam Parmar, Shailendra Wasnik. The design of colon-specific drug delivery system and different approaches to treat colon disease. International Journal of Pharmacuetical Sciences Review and Research. 2011;6(2):167-77.
  2. DinaNath Mishra, Dinesh Kaushik, Satish Sardana. Implications of biodegradable and bioadhesive systems in colon delivery. International Journal of Pharmacuetical Sciences and Drug Research. 2009;1(2):55-62.
  3. Manivannan Rangasamy. Colon targeted drug delivery systems: A review. International Journal of Drug Fomulation and Research. 2010;1(2):30-54.
  4. Anil K Philip, Betty Philip. Colon targeted drug delivery systems: A review on primary and novel approaches. Oman Medical Journal. 2010;25(2):70-8.
  5. Thiruganesh R, Uma Devi SK, Suresh S. Preparation and characterization of pectin pellets of Aceclofenac for colon targeted drug delivery. J. Chem. Pharm. Res. 2010;2(1):361-74.
  6. Manish Neekhra, Sarika Shrivastav, Sarvesh Sharma, KI Molvi, Vimal Kumar. Development and evaluation of oral colon targeted Ketorolac tromethamine capsule International Journal of Pharmacuetical Sciences and Research. 2010;1(5):61-7.
  7. Chetan Singh Chauhan, Pushpendra Singh Naruka, Rajendrapal Singh Rathore, Viralkumar Badadwal. Formulation and evaluation of Prednisolone tablet for colon targeted drug delivery system. J. Chem. Pharm. Res. 2010;2(4):993-8.
  8. Rajendra Jangde. Microsponge for colon targeted drug delivery system: An overview, Asian Journal of Pharmaceutical Technology, 2011, 1(4), 87-93.
  9. Balfour JA, Fitton A, Barradell LB. Lornoxicam. A review of its pharmacology and therapeutic potential in the management of painful and inflammatory conditions. Drugs. 1996, 51(4): 639-57.
  10. Vikas Jain and Ranjit Singh. Development and characterization of Eudragit RS 100 loaded microsponges and its colonic delivery using natural polymers, Acta Poloniae Pharmaceutica Drug Research, 2010, 67(4): 407-415
  11. Comoglu T., Gonul N., Baykara T. Preparation and in vitro evaluation of modified release ketoprofen microsponges. Farmaco, 2003, 58(2): 101-106.
  12. Mine Orlu, Erdal Cevher, Ahmet Araman. Design and evaluation of colon specific drug delivery system containing flurbiprofen microsponges. 2006, 318(1-2): 103-117.
  13. Chickpetty SM, Raga Baswaraj. Studies on design and in-vitro evaluation of compression coated delivery systems for colon targeting of Diclofenac sodium. International Journal of PharmaTech Research CODEN(USA):IJPRIF. 2010;2(3):1714-22.
  14. Ghule prashant J, Karle Ganesh D, Saumya Das. Formulation and In-vitro evaluation of colon targeted drug delivery of Aceclofenac. Journal of Pharmacy Research. 2010;3(5):1082-86.
  15. Rasika D Bhalke, Raosaheb S Shendge, Fatima J Sayyad, Kishore S Salunkhe. Development of colon specific drug delivery of Aceclofenac by using effective binder system of ethyl cellulose. International Journal of Pharma and Biosciences. 2010;1(3):1-5.
  16. Uma Devi SK, Thiruganesh R, Suresh S. Preparation and characterization of chitosan tablets of Aceclofenac for colon targeted drug delivery. Journal of Pharmaceutical Research and Health care. 2010;2(1):46-65.

09 /

SIGNATURE OF CANDIDATE

/ (TODMOD SAMREEN SARDAR MEHRUNISSA)
10 / REMARKS OF THE GUIDE / The proposed work is a novel concept of delivering the drug with reduced side effects which will improve patient compliance. Hence recommended for registration.
11 / 11.1 NAME AND DESIGNATION OF GUIDE
(IN BLOCK LETTERS) / M.A.SALEEM M.Pharm.
ASSOCIATE PROFESSOR & HOD,
Department of Pharmaceutics,
LuqmanCollege of Pharmacy,
BEHIND P & T Colony, OLD Jewargi Road,Gulbarga.
11.2 Signature
11.3 Co-Guide / --
11.4 Signature / --
12 / 12.1Remarks of the Chairman & Principal / We will provide all necessary facilities required for the proposed research work.
So, recommended for registration.
12.2Signature