“FORMULATION AND EVALUATION OF ENTERIC COATED PIROXICAM LOADED BEADS”

MASTER OF PHARMACY DISSERTATION PROTOCOL

SUBMITTED TO THE

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA, BANGALORE

BY

MR.SANJAY.KB.Pharm

M.PHARM – I

Under The Guidance of

VIRESH K. CHANDURM. Pharm

ASST.PROFESSOR

DEPARTMENT OF PHARMACEUTICS

SRINIVAS COLLEGE OF PHARMACY, VALACHIL, MANGALORE – 574143

2013-2015

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. / Name of the Candidate and Address: / MR.SANJAY.K
1stYEAR M.PHARM, DEPT. OF
PHARMACEUTICS,
SRINIVAS COLLEGE OF PHARMACY,
VALACHIL, MANGALORE-574143.
2. / Name of the Institution: / SRINIVAS COLLEGE OF PHARMACY,
VALACHIL, FARANGIPETE POST, MANGALORE-574143.
3. / Course of Study and Subject: / MASTER OF PHARMACY
(PHARMACEUTICS)
4. / Date of Admission: / 25 JULY2013
5. / Title of the Project:
“FORMULATION AND EVALUATION OF ENTERIC COATED PIROXICAM LOADED BEADS”
Brief Resume of the intended work:
Need of the study:
Oral delivery is the most desirable and preferred method of administrating therapeutic agents for their systemic effects. Despite tremendous advancement in the drug delivery system, oral route remains the preferred route for the administration of therapeutic agents and because of low cost therapy and ease of administration leads to higher levels of patient compliance. Conventional oral dosage forms such as tablets and capsules provide specific drug concentration in systemic circulation without offering any control over drug delivery and also cause great fluctuations in plasma drug levels. The design of oral controlled drug delivery system should be primarily aimed to achieve more predictable and increased bioavailability.1,5
For the last two decades, there has been an enhanced demand for more patient-compliant dosage forms. Oral administration is the most popular route due to ease of ingestion, pain avoidance, versatility (to accommodate various types of drug candidates) and most importantly, patient compliance.
NSAID drugs having analgesic and anti-inflammatory effects are widely administered orally in treatment of mild or severe pain mainly for rheumatoid arthritis and osteoarthritis patients. A trend in NSAID development has been to improve therapeutic efficacy and reduce severity of upper GI side effects through altering dosage forms of NSAIDs by modifying release of formulations to optimize drug delivery. These formulations are designed to increase patient compliance through a prolonged effect and reduce side effects through lowered peak plasma concentration.1,5
Osteoarthritis or degenerative joint disease is the most common form of chronic disorder of synovial joints. It is characterized by progressive degenerative changes in thearticular cartilages over the years, particularly in weight-bearing joints. Rheumatoid arthritis (RA) is a chronic multisystem disease of unknown cause. RA is a common disease having peak incidence in 3rd to 4th decades of life, with 3-5 times higher preponderance in females.3
Piroxicam is a long acting potent NSAID with anti-inflammatory potency similar to indomethacin and good analgesic-antipyretic action. It is a reversible inhibitor of COX; lowers PG concentration in synovial fluid and inhibits platelet aggregation-prolonging bleeding time. Piroxicam is rapidly and completely absorbed: 99% plasma protein bound; largely metabolized in liver; excreted in urine and bile; plasma t½ is long-nearly 2 days. Steady state concentrations are achieved in a week.4
Microencapsulation has become a common technique in production of controlled release dosage forms. One such approach is the production of polymeric gel beads. The beads are discrete spherical microcapsules that serve as solid substrate on which drug is coated or encapsulated in the core of beads.2,5
Enteric coating:
This is a process by which drugs are designed to show local action in the intestines without undergoing disintegration and drug release in the stomach. This process depends on pH factors. The dosage form is coated in such a way that it resists dissolution in the acidic gastric fluids but dissolves in the alkaline environment of intestines.
Some of the reasons for enteric coating are:
1. It protects acid sensitive drugs from gastric fluid. e.g., enzymes and certain antibiotics.
2. To prevent gastric distress or nausea due to irritation from a drug, e.g., Sodium salicylate.
3. To provide a delayed-release component for repeat-action drugs.
4. To deliver drugs that are optimally absorbed in the small intestine to their primary absorption site in their most concentrated form.2,5
In the present work an attempt made to design and development of enteric coated beadscontainingPiroxicam for the effective management of rheumatoid arthritis and osteoarthritis.
The aim of this study is to design and evaluate enteric coated beads of Piroxicam. The new dosage form was obtained by Ionotropic gelation-coacervation method.

Review of literature:
  • Radhika PR, Sadu B, Lakshmi PS, Rani E, Sivakumar Thave designed the enteric coated beads of Naproxen using cellulose acetate phthalate(CAP) as enteric coating polymer.The beads were prepared by ionotropic gelation technique. Various studies were carried out such as angle of repose, drug entrapment efficiency and In-vitro release studies. In-vitrorelease studiesshowed that the enteric coated beads are suitable for further pharmaceutical manipulation(eg:capsule filling) and drug release showed first order kinetics. It was one step production technique,since it does not need a coating process. Beads with high drug loading could be prepared.5
  • Kamble RS, Kajale AD, Giradkar KP, Bakade BV, Channawar MA, Chandewar AVformulated enteric coated dosage form of ketorolac tromethamine by direct compression method and eudragit L as enteric coating polymer. In-vitro drug release comparison was studied of different polymers like xanthum gum, guar gum, sodium alginate, ethyl cellulose. It was concluded that formulation having xanthum gum shows more release retardant properties compared to others.6
  • Girhepunje KM, Krishna P, Ranju SP, Hitesh BG, Thirumoorthy N have formulated the Celecoxib loaded microbeads for the targeted drug delivery system for colo-rectal cancer by using inclusion complex with sodium alginate, eudragit FS 30-D and evaluated for entrapment efficiency, FT-IR, DSC, SEM, In-vitro drug release, In-vitro cell line study and cytotoxicity screening.7
  • Goudanavar PS, Bagali RS, Patil MS, Shekara CSprepared diclofenac sodium microbeads using HPMC and chitosan as drug release modifiers & concluded that micro encapsulation ionotropic gelation technique is inexpensive, prevented drug related adverse effects and drug entrapment efficiency nearly reached 95%. Mechanism of drug release was found to be followed super case-2 transport.8
  • Manjanna KM, Rajesh KS, Shivakumar Bprepared and evaluated calcium alginate beads with calcium chloride as cross linking agent for aceclofenac sodium by ionotropic external gelation method and the polymers acted as drug release modifiers. The entire process found to be feasible.9
  • Manjanna KM, Shivakumar B, Pramod KTMprepared Diclofenac microbeads using sodium alginate as the hydrophilic carrier in combination with HPMC, chitosan and pectin polymers as drug release modifiers in various proportions to overcome the drug related adverse effects, improve drug bioavailability in different GI tract conditions. All investigated properties shows satisfactory results.10
  • Khazaeli P, Pardakhty A, Hassanzadeh Fhas formulated ibuprofen beads by ionotropic gelation using alginate and various cross linking agents. Characterisation of the beads, size distribution, entrapment efficiency of drug and drug release kinetics were investigated. The studies was found to be satisfactory.11
• Williams RO and Liu J evaluated the effects of fluidised-bed processing and curing conditions for beads coated with an aqueous cellulose acetate phthalate dispersion. The coating temperature was found to be critical parameter. Heat-only curing had no significant effect on reducing the drug release, except for the batch coated at the lowest temperature. Exposure of the beads to elevated humidity during curing enhanced coalescence of the film and the mechanical strength of film. The degree of improvement was dependent on the curing temperature, % humidity, curing time and the history of coating conditions. These findings supported the importance of controlling the processing and curing conditions to enhance post-coating polymer coalescence for beads coated with aqueous CAP.12
  • Kumar SS, Kumar SA, Mahajan AA, Pathak NS, Upadhyay S, Pratap V, et al. have developed colon targeted drug delivery of an anti-amoebic drug Tinidazole by Ionotropic gelation and Coacervation phase separation technique using Sodium alginate and Eudragit S100. Microspheres prepared by using Tinidazole core: ES-100 ratio 1:4, stirring speed 600 rpm and 0.2% conc. of Span 80 were reported as an optimized formulation. They concluded that Eudragit S-100 coated Sodium alginate microspheres have the potential to be used as carrier for an effective colon targeted delivery system.13
  • Raj BS, Punita B, Janki B have formulated the chitosan Prazosin beads by ionotropic gelation method and crosslinking with sodium tripolyphosphate. The prepared beads were evaluated for bead size and shape, drug entrapment efficiency and In-vitro drug release study for 7 hours. It showed a sustained release pattern. Prazosin release decreased with an increase in concentration of chitosan.14
  • Manjann KM, PramodKTM, Sivakumar B have formulated the Dexibuprofen-alginate clay composite microbeads for oral controlled drug deliveryby using micro emulsification ionotropic gelation method with the help of calcium chloride as crosslinking agent and the solid microemulsionmicrobeads were evaluated for mean particle size, shape and surface characteristics by SEM, Drug polymer interaction by FT-IR, Drug entrapment efficiencyand In-vitrodrug release.15
  • Prajapathi BG, Patel RP & Patel BChave developed the taste masked, orally disintegrating tablets of piroxicam & evaluated by taking considerations of uniformity of weight, crushing strength etc. The present study concluded that orally disintegrating tablets can be formulated using superdisintegrants properly distributed in suitable solvents used for granulation. Eudragit EPO was found to be a good candidate to mask the bitter taste of the drug.16
  • Reddy KA and Venugopal K have formulated the buccal tablets of piroxicam by using carbopol 934 as mucoadhesive polymers & evaluated In-vitro drug release studies, In-vitro mucoadhesive strength measurement, moisture absorption test, In-vitro retension time, surface PH& In-vitro drug permeation. The FTIR results showed no evidence of indication between the drug and polymers. The results indicate that suitable bioadhesive buccal tablets with desired permeability could be prepared.17
  • Kumar AA, Kumar PR, Anil KA, Reddy KL, Murthy GK et al., have formulated Aceclofenac microcapsules by employing ionotropic gelation using methyl cellulose, sodium CMC, HPMC, and they are evaluated for particle size distribution and size analysis, angle of repose, drug content, microencapsulation efficiency &In-vitro release studies. The In-vitro release studies indicated sustained release of Aceclofenac from the formulation.18
  • Khodakiya A, Raval M, Khodakiya M, Patel B, Patel LD developed SR beads of aspirin by ionotropic gelation technique by using sodium alginate as biopolymer. The beads were coated with CAP enteric polymer. The processing parameters like drug polymer ratio and the beads were evaluated for flow properties, particle size, %drug entrapment and In-vitro drug release were studied. It was found that concentration of polymer has profound effect to control and sustain the release of aspirin.19
Objectives of the study:
The objectives of the study are to formulate enteric coated Piroxicam beads with the purpose of developing a dosage form for very quick onset of action.
Specific objectives of the present investigation are as follows:
1. To carry out preformulation study of the drug.
2. To carry out drug-polymer interaction by FTIR studies.
  1. Formulation of Enteric coated beads of Piroxicam.
  2. To evaluate the physical parameters like shape, surface morphology &
particle size.
  1. To estimate the drug content & encapsulation efficiency
  2. To evaluate theIn-vitro drug release characteristic of the formulation.
  3. To carry out stability studies as per ICH guidelines.

Materials and Methods:
Materials:
  1. Drug:Piroxicam
  2. Polymers:Cellulose acetate phthalate, Polyvinyl acetate pthalate, Cellulose acetate succinate, HPMC, PEG etc.
  3. Excipients: Sodium sulphate, Sodium bicarbonate, Citric acid, Sodium hydroxide, Disodium hydrogen phosphate, Concentrated hydrochloric acid, Methanol, etc.
All ingredients are of analytical grade.
Methods:
  • Preformulation studies
  1. Determination of drug excipient compatibility by FTIR.
  • Formulation of enteric coated beads
  1. Preparation and Encapsulation by Ionotropic gelation technique.5,8,11,13,14,18,19
  2. Enteric coated beads are filled in capsules.5,8,11,13,14,18,19
  • Evaluation studies
  1. Shape and surface morphology by SEM.5,6,7,15
  2. Particle size distribution analysis.5,8,11,13,14,18,19
  1. Flow properties. 5,8,11,13,14,18,19
  2. Drug content by UV Spectrophotometer.5,18,19
  3. Drug entrapment efficiency.5,8,11,13,14,18,19
  • In-vitro drug release study5,7,8,11,13,14,17,18,19
  • Stability studies as per ICH guidelines.

Source of data:
Review of literature from
a)Journals such as
Journal of Chemical and Pharmaceutical Research.
International Journal of Research in Pharmaceutical and Biomedical Sciences.
International Journal of Pharmaceutical Research.
International Journal of Biomedical Research.
Asian Journal of Pharmacy and Medical Science.
Journal of Pharmacy Research.
Scholars Research Library.
Current Research and Information on Pharmaceutical Sciences.
International Journal of PharmTech Research.
International Research Journal of Pharmacy.
American Journal of PharmTech Research.
European Journal of Pharma and Bio Sciences.
Iran Journal of Pharmaceutical Sciences.
International Journal of Current Pharmaceutical Research.
b)Internet Browsing
Method of Collection of Data:
  • Data on drug and Excipients will be collected from the drug information centre, Patents, Reference books, Text books, catalogs etc.
  • Data will be collected from the prepared formulations, In-vitrodissolution studies and stability studies as per ICH Guidelines.
Does the study require any investigations or interventions to beconducted on patients or other humans or animals? If so, please describe briefly.
- Not applicable
Has ethical clearance been obtained from your institution in case of 7.3?
-Not applicable
List of references:
  1. Mradul R, Kapoor R, Sudeesh MS, Patil UK. An applauded novel drug delivery system for arthritis using NSAIDs by microencapsulation technique- A review Der Pharmacia letter 2010; 2(4):335-54
  1. Lachmann L, Liebermann AH. Theory and Practice of Industrial Pharmacy.Special Indian edition; 2009:412-29
  1. Harsh M. Textbook of pathology. 5th ed. Jaypee Brothers Medical Publishers(P)LTD NewDelhi; 2005:875-76
  1. Tripathi KD. Essentials of Medical Pharmacology. 5th ed. Jaypee Brothers Medical Publishers(P)LTD NewDelhi; 2003:178
  1. Radhika PR, Sadu B, Lakshmi PS, Rani E, Sivakumar T. Enteric Coated Beads of Naproxen: Design, Development and Evaluation. Int J PharmTech Res 2012; 4(4):1770-76

  1. Kamble RS, Kajale AD, Giradkar KP, Bakade BV, Channawar MA, Chandewar AV. Formulation and Development of Enteric coated dosage form using Ketorolac Tromethamine. Int J Pharma Res Dev 2010; 2(8):126-35
  1. Ghihepunje KM, Krishna P, Ranju SP, Hitesh BG, Thirumoorthy N. Celecoxib loaded microbeads- A targeted drug delivery for colorectal cancer. Int J Cur Pharm Res 2010; 2(1):46-55.
  1. Goudanavar PS, Bagali RS, Patil MS, Shekara CS. Design and characterization of diclofenac sodium microbeads by ionotropic gelation technique. Int J Pharma BioSci 2010; 1(2):1-10
  1. Manjanna KM, Rajesh KS, Shivakumar B. Formulation and optimization of natural polysaccharide hydrogel microbeads of aceclofenac sodium for oral controlled drug delivery. Ame J Med Sci 2013;1(1):5-17
  1. Manjanna KM, Shivakumar B, Pramod KTM. Diclofenac Sodium Microbeads for Oral Sustained Drug Delivery. Int J PharmTech Res 2009; 1(2):317-27.
  1. Khazaeli P, Pardakhty A, Hassanzadeh F. Formulation of ibuprofen beads by ionotropic gelation. Iran J Pharm Res 2008; 7(3):163-70
  1. Williams RO, Liu J. Influence of processing and curing conditions on beads coated with an aqueous dispersion of cellulose acetate phthalate. Eur J Pharma Biopharm 2000; 49(3):243-52
  1. Kumar SS, Kumar SA, Mahajan AA, Pathak NS, Upadhyay S, Pratap V, et al. Formulation and Evaluation of Colon Targeted Drug Delivery of an Anti-Amoebic Drug. Int J Pharm Invest 2012;2(2):138-52.

  1. Raj BS, Punita B, Janki B. Formulation and evaluation of chitosan prazosin beads by ionotropic gelation method. Int J Res Pharm chem 2012; 3(2):974-83.
  1. Manjann KM, PramodKTM, Sivakumar B. Formulation and evaluation of Dexibuprofen alginate-clay composite microbeads for oral controlled drug delivery. Asian J Pharm Sci 2012; 7(1):28-39.
  1. Prajapathi BG, Patel RP & Patel BC. Development and Characterization of Taste masked, Orally Disintegrating Tablet of Piroxicam. Int J Pharma Sci 2010; 1(1):35-47
  1. Reddy KA, Venugopal K. Formulation & In-vitro evaluation of buccal tablets of piroxicam. Int J Chem Sci 2012; 10(1):399-412.
  2. Kumar AA, Kumar PR, Anil KA, Reddy KL, Murthy GK et al., Formulation design of aceclofenac microcapsules by ionotropic gelation technique, characterization studies and release kinetics. J Applied Pharm Sci 2001; 1(6):127-32.
  3. Khodakiya A, Raval M, Khodakiya M, Patel B, Patel LD. Formulation development of sustained release aspirin beads for intestinal delivery. Int J Pharm Sci Rev Res 2012; 16(1):38-46


Signature of the candidate / (SANJAY K)
Remarks of the Guide / The work, which is assigned to
Mr.Sanjay K is under my guidance.
11.1 Name and Designation of the
Guide / Viresh K ChandurM.Pharm
Asst.Professor,
Department of Pharmaceutics
Srinivas College of Pharmacy
Valachil, Mangalore- 574143
11.2 Signature
11.3 Name and Designation of the
Co-Guide / _ _ _ _ _
11.4 Signature / _ _ _ _ _
11.5 Head of the Department / Dr. A. R. SHABARAYA M.Pharm,Ph.D.
Principal and Director,
Department of Pharmaceutics,
SrinivasCollege of Pharmacy,
Valachil, Mangalore- 574143
11.6 Signature
12.1 Remarks of the Principal / Recommended and forwarded for favourable consideration.
12.2 Signature / Dr. A. R. SHABARAYA
(principal & director)