Formulation and Evaluation of Orodispersible Tablets of Piroxicam

Formulation and Evaluation of Orodispersible Tablets of Piroxicam

FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OF PIROXICAM

M. PHARM DISSERTATION PROTOCOL

SUBMITTED TO THE

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA

BY:

RAJKUMAR MALSHETTY

B. Pharm

UNDER THE GUIDANCE OF

DR. K SREENIVASA RAO

M. Pharm PhD.

Professor & Principal

DEPARTMENT OF PHARMACEUTICS,

RRKSCOLLEGE OF PHARMACY,

NAUBAD, BIDAR-585402,

KARNATAKA.

2011-12

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA,

BANGALORE,

ANNEXURE - II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR M.PHARM DISSERTATION

1. / Name of the candidate
And address. / RAJKUMAR MALSHETTY
Sri Krishna Niliya,Plot No-175, Old Adarsh Colony (Behind KEB)Bidar-585401
2. / Name of Institution / RRKS’s College of Pharmacy,
Naubad, Bidar-585 402
3. / Course of study and subject. / M. Pharmacy
(Pharmaceutics)
4. / Date of admission to the course / 10-12-2012
5. / Title of Topic / FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OF PIROXICAM

6. BRIEF RESUME OF THE INTENDED WORK:

6.1. Need for the study:

The tablet is the most widely used dosage form because of its convenience in terms of self-administration, compactness, and ease in manufacturing. However, geriatric and pediatric patients experience difficulty in swallowing conventionaltablets, which leads to poor patient compliance. To overcome this weakness, scientists have developed innovative drug deliverysystems known as orally disintegratingtablets(ODTs)1.which disintegrates anddissolves rapidly in saliva without the need ofswallowing with drinking water since the tabletis placed in the mouth where it dispersesrapidly before swallowing2.

Orodispersible tablets are those which disintegrate or dissolved in saliva without the need of water. As tablet disintegrates in mouth this could enhance the clinical effect of the drug through pre-gastric absorption from the mouth, pharynx and esophagus. In such cases bioavailability of drug is significantly greater than those observed from conventional dosage form by avoiding first pass metabolism3.

Recently, useful dosage forms, such as rapidly disintegrating or dissolving tablets, have beendeveloped and applied clinically. When such tablets are placed in the oral cavity, saliva quickly penetrates into the pores to cause rapid tablet disintegration. Currently, it has been revealed that a fast dissolving tablet prepared by a technique like lyophilization, vaccum drying technique, direct compression method , disintegrant addition technique and sublimation technique by using sublime agent like camphor, menthol4.

Piroxicam is a Non steroidal anti-inflammatory(NSAID) drug.Chemically Piroxicam is 4-Hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide. And it is white or slightly yellow, crystalline powder. Slightly soluble in water, soluble in dichloromethane5. Piroxicam is used as an effective analgesic and anti-inflammatory agent in rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and acute pain in musculoskeletal disorder and acute gout.

In the present study, an attempt will be made to formulate orally disintegrating tablets of Piroxicam with a view to provide a convenient mean of administration to those patients suffering from difficulties in swallowing such as pediatrics and geriatrics, un-cooperative and mentally ill patients.

6.2 Review of literature:

Literature survey on the topic has been done and very prominent are:

Mahajan HS et al6., prepared Mouth dissolving tablets of Sumatriptan succinate by direct compression method using superdisintegrants like sodium starch glycollate, carboxy methyl cellulose sodium and treated agar. Combination of sodium starch glycollate and carboxy methyl cellulose was found to give best result.

Shirwaikar AA et al7., prepared Atenolol was formulated as Fast disintegrating tablet using three super disintegrants like sodium starch glycollate, crosscarmellose sodium, crosspovidone at different concentrations. Crosscarmellose sodium was proved to be best among the three.

D.V. Derle et al8.,developed Microemulsion as a vehicle for Transdermal Permeation of Nimesulide. a pseudoternary phase diagram was constructed to determine the composition of an aqueous phase, an oil phase and surfactant: co-surfactant(2:1, 3:1, 4:1) phase that will yield a ME. No significant differences wasobserved between the release rates of nimesulide from both formulations despite their difference in alcohol content.

Shishu et al9., prepared Chlorpheniramine malate rapidly disintegrating tablets were prepared by using taste masked granules of aminoalkyl metha crylate copolymer (Eudragit E-100) by extrusion method, and were found oral fast disintegrating tablets which had good taste and disintegrated in the oral cavity within 30 seconds.

Omaima AA et al10.,prepared formulated and optimized mouth dissolving tablets containing Rofecoxib Solid Dispersion. The solid dispersions were prepared by using PVP (K30) by solvent evaporation method. The solid dispersions were found to have enhanced solubility and improved dissolution profile.

Mohsin A A. et al11., prepared fast dissolving tablets of the drug Amitriptyline hydrochloride using superdisintegrants such as Croscarmellose sodium (Ac‐Di‐Sol), Sodium starch glycolate (Explotab) and Crospovidone by direct compression technique. Tablets containing Crospovidone showed better disintegrating character along with the rapid release. No appreciable difference was found between the formulations containing other two superdisintegrants. Crospovidone was found to be better suited for the formulation of mouth dissolving tablet of Amitriptyline hydrochloride compared to other superdisintegrants used in the study.

Swamy PV et al12., developed orodispersible tablet of meloxicam using different superdisintegrants. Combinations of sodium starch glycolate-croscarmellose sodium or sodium starch glycolate-crospovidone were used along with directly compressible mannitol. The prepared batches evaluated for hardness, friability, wetting time, water absorption ratio like various parameters. He concluded that the formulation prepared using 2% w/v sodium starch glycolate and 15% croscarmellose sodium was found better formulation compare to conventional tablet.

Abdelbary C et. al.,13 determined the in-vitro disintegration profile of RDT and correlate with oral disintegration. They evaluated the disintegration profile of RDT manufactured by main commercialized technologies, using texture analyzer. The evaluation of quantitative values as the disintegration onset (t1) and total disintegration time (t2), the characterization of effects of test variables as the disintegration medium and temperature on the disintegration time of RDT and correlation between in-vitro and in-vivo oral disintegration times. Which showed that the use of the texture analyzer in-vitro determination of the disintegration, behaviors different RDT was shown very successful, convenient and precise

Mohammed S. Khan. et al14., prepared piroxicam floating microspheres for prolonged gastric retention by solvent evaporation method using polymers hydroxypropylmethyl cellulose and ethyl cellulose. It was observed there is no significant effect of the stirring rate during preparation on drug release was observed.

S. Velmurugan. Et al15., prepared Buccal tablets of Piroxicam by Using HPMC K4M and Carbopol 934 as Mucoadhesive polymers. In this present study H# formulation comprises of Piroxicam and HPMC K4M (1:3) showed optimum drug release and satisfactory bioadhesive properties.

6.3Objective of the study:

The basic objective of this work is to develop an Orodispersible tablet of Piroxicam which is a potent non-steroidal anti-inflammatory drug, which preferentially inhibits COX-2.

Tablet disintegrates and disperses in oral cavity within 30 seconds without the need of drinking water and has pleasant mouth feel and there is no after taste or grittiness.

Successfully discriminates the ability of three superdisintegrants to promote drug dissolution and proposes a model formulation for disintegrant performance testing and quality control purposes.

To permit the arbitrary selection of a batch of tablets with improved dissolution profile and subsequently good bioavailability.

7. MATERIALS AND METHOD:

7.1 Source of data:

  • Internet.
  • (Helinet).
  • RRKS College Library, Bidar
  • International Pharmaceutical Abstract.

7.2 Materials:

Drug:PIROXICAM.

Chemicals:

Directly Compressible Filler: Microcrystalline cellulose, Mannitol, etc

Sublimating agent: Camphor or Menthol, etc

Fast Disintegrant: Croscarmellose Sodium, Crospovidone, Sodium starch

glycolate etc.

Sweetener: Aspartame.

Flavorant: Mixed fruit flavor.

Glidant:Talc or Colloidal silicon dioxide.

Lubricant: Magnesium stearate.

7.3 Methods of the preparation of Orodispersible tablets:

a)Direct compression: In this method, addition of superdisintegrants in optimum concentration so as to achieve rapid disintegration along with good mouth feels. Superdisintegrants like sodium starch glycollate, crosspovidone, croscarmallose sodium etc; will be used.

b)Sublimation: In this method, mannitol is used as diluent and camphor as a volatile material to prepare highly porous compressed tablets. After compression tablets will be heated in hot air oven at 800 C until a constant weight is obtained to ensure that complete removal of volatilisable component.

c)Use of sugar based excepients: In this method, highly soluble sugar based excepients such as aspartame, dextrose, fructose, etc; are used in order to produce disintegration with good taste masking.

7.4Evaluation ofMouth dissolving tablets:

Various Orodispersible tablet formulations of Piroxicam will be formulated and evaluated for hardness, friability, weight variation, disintegration time, drug content, In vitro dissolution rate, short-term stability and drug excepients interaction (IR spectroscopy).

a)Estimation of Drug content: The drug content of Orodispersible tablets will be determined spectrophotometrically at 334 nm.14

b)Disintegration time: Disintegration time of the Orodispersible tablets will be determined by using distilled water at 37±20C as a medium using tablet disintegration test apparatus (USP).

c)In vitro dissolution study: In vitro drug release study of the prepared Orodispersible tablets will be carried in 900ml of 6.8 pH phosphate buffer tablet dissolution tester using paddle stirrer at 100 rpm.14

d)Short term stability: Promising Orodispersible tablets of the drug will be stored at a temperature of 40±20C with 75±5% relative humidity for 1 month and evaluated for drug content, disintegration time and drug-excepients interaction.

7.5 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 work ------

7.6 Has ethical clearance been obtained from your institution in case of 7.5.

------Not applicable ------

8. LIST OF REFERENCES:

1)Ketan RM, et al. “Formulation, Design and Optimization of Orodispersible Tablets of Atenolol.”Int J. PharmTech. Res. 2009; Vol 4: 1559-1563.

2)Jashanjit S, Rajmeet singh. “Optimization and Formulation of Orodispersible Tablets of Meloxicam.”Tropical J. Pharm. Res. 2009; Vol 8(2): 153-159.

3)Sreenivas SA, et al. “Orodispersible Tablets: New-fangled Drug Delivery System-A Review.” Indian J. Pharm. Educ. Res. 2005; Vol 39: 177-180.

4)Uddhav B, et al. “Formulation and Evaluation of sublimed Fast Melt Tablets of Levocetirizine Dihydrochloride.” Int J Pham. Sci. 2010; Vol 2(2): 76-80.

5)Martindale, The complete drug reference, 34 editions, Page 84.

6)Mahajan HS, Kuchekar BS and Badhan AC. “Mouth dissolving tablets of Sumatriptan succinate.”Indian J Pharm Sci., 2004 Jul-Aug; 238-340.

7)Shirwaiker AA, Ramesh A. “Fast disintegrating tablets of Atenolol by Dry granulation method.”Indian J. Pharm. Sci,. 2004; 66(4): 422-426.

8)D.V. Derle, B.S.H Sagar, et al. “Microemulsion as a vehicle for transdermal permeation of nimesulide.”Indian Journal of Pharmaceutical Sciences, 2006; 68(5): 622-625.

9)Shishu, Ashima Bhatti and Tejbir Singh. “Preparation of Tablets Rapidly Disintegrating in Saliva containing Bitter Taste-Masked Granules by Compression Method.”Ind. J. Pharm. Sci. 2007; 69(1): 80-84.

10)Omaima A. Sammour, Mohammed A.Hammad, Nagia A. Megrab, Ahmed S. Zidan. “Formulation and Optimization Of Mouth Dissolve Tablets Containing Rofecoxib Solid Dispersion.”AAPS Pharm. Sci. Tech. 2006; 7(2) Article 55: E1-E8.

11)Mohsin AA , Nimbalakar NE, Sanaullah S, and Aejaz A.“Formulation And Evaluation Of Mouth Dissolving Tablets Of Amitriptyline Hydrochloride By Direct Compression Technique.”Int. J. Pharm. & Pharma. Sci. 2010; 2 (1): 204-210.

12)Swamy PV, Areefulla SH, Shirand SB, Gandra S, and Prashant B. “Orodispersible tablets of meloxicam using disintegrant blend for improved efficacy.”Ind. J.Pharm. Sci. 2007; 69(6): 836-840.

13)Abdelbary G, Prinderre.P, Eouani C, Joachim J, and Reynier JP. “Determination of
in vitro disintegration profile of rapidly disintegrated tablet and correlation
with oral disintegration.” Int. J. Pharm. 2005; 292: 29-41.

14) Mohammed S. Khan, Gowda D.V, and Afifa Bathool. “Formulation and Characterization of Piroxicam floating microspheres for prolonged gastric retention”. Scholar Research Library. 2010; 2(6): 217-222.

15)S. Velmurugan, B. Deepika, K.Nagaraju, and Sundar Vinushitha. “Formulation and in-vitro Evaluation of Buccal Tablets of Piroxicam”. Int. J. PharmTech. Res. 2010; 2(3): 1958-1968.

9. / Signature of the candidate / ( RAJKUMAR MALSHETTY)
10. / Remarks of the Guide
11. / Name and Designation of
(in block letters)
11.1Guide
11.2Signature / DR. K. SREENIVASA RAO
M.Pharm, Ph.D
PROFESSOR & PRINCIPAL
DEPARTMENT OF PHARMCEUTICS
RRKS COLLEGE OF PHARMACY
NAUBAD, BIDAR.
12. / Name and Designation
(In block letters) / NOT APPLICABLE
12.1Co – Guide
12.2Signature / ------
------
13 / 13.1Head of the Department
13.2 Signature / DR. K. SREENIVASA RAO
M.Pharm, Ph.D
PROFESSOR & PRINCIPAL
DEPARTMENT OF PHARMCEUTICS
RRKS COLLEGE OF PHARMACY
NAUBAD, BIDAR.-585402
KARNATAKA
14. / 14.1Remarks of the Chairman
and Principal.
14.2Signature / ( DR. K SREENIVASA RAO )