Formulation and Evaluation of Palatable Fast Dissolving

FORMULATION AND EVALUATION OF PALATABLE FAST DISSOLVING

TABLETS OF LORNOXICAM BY USING IONEXCHANGE RESINS

M.Pharm dissertation protocol submittehd to

Rajiv Gandhi University of Health Sciences, Karnataka

Bangalore – 560041

MS.BANDI MOUNICA B.Pharm

Under the Guidance of

DR.ROOPA KARKIM.Pharm, Ph.d

Professor HOD

Department of Industrial Pharmacy

Acharya & B.M.Reddy College of Pharmacy

Soldevanahalli,Chikkabanavara (Post)

Hesarghatta main road, Bangalore – 560 090

2010– 2012

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

KARNATAKA, BANGALORE.

ANNNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1 / Name and address of candidate / BandiMounica,
c/o V.Veerendra Rao,
D.NO:8-392,
L.M.B Colony,
Mangamoor Donka,
Ongole-523002,
Prakasam(Dist),
Andhra pradesh.
2 / Name of institution / ACHARYA & B.M. REDDY COLLEGE OF
PHARMACY.
Soldevanahalli, Hesarghatta Main Road,
Chikkabanavara Post.
Bangalore-560090
3 / Course of study and subject / M. Pharm
(Industrial Pharmacy)
4 / Date of admission /

04-09-2010

5 / Title of the project / FORMULATION AND EVALUATION OF PALATABLE FAST DISSOLVING TABLETS OF LORNOXICAM BY USING IONEXCHANGE RESINS
6
6.1 / BRIEF RESUME OF INTENDED WORK
NEED FOR THE STUDY:
Non steroidal anti inflammatory drugs (NSAID’s) are the ones with analgesic and antipyretic effects which also have anti inflammatory action in higher doses. NSAID’s are usually indicated for the treatment of acute or chronic conditions of pain and inflammation and are prescribed for the symptomatic relief of the arthritis1.
Arthritis which is defined as the inflammation of joints leading to their damage, can be classified into various types like
1)Rheumatoid arthritis
2)Osteoarthritis
3)Gout
4)Psoriatic arthritis
Rheumatoid arthritis is an autoimmune disorder that causes the immune system to attack the joints where it causes inflammation (arthritis) and destruction. It can also damage some organs such as the lungs and skin. Studies have shown that this type of arthritis is more common in women than in men.
Osteoarthritis also known as degenerative arthritis or degenerative joint disease is a clinical syndrome in which low grade inflammation results in pain in the joints caused by abnormal wearing of the cartilage that covers and act as a cushion inside joints and destruction or decrease of Synovial fluid that lubricates those joints.
The anti arthritis drug formulation is a challenge to the pharmacist in the present world. The present work will be focused on to formulate fast dissolving tablets by using NSAID’s. The NSAID’s are the first choice of the drugs used in the treatment of fever, pain and inflammation in the body. The non-selective COX inhibitors have recently been found to be very effective in the treatment especially for arthritis2.
E.g. Lornoxicam, Meloxicam, Piroxicam and some other NSAID’s.
Lornoxicam is a non-steroidal anti-inflammatory drug with analgesic property and belongs to the class of Oxicams. Lornoxicam inhibits the synthesis of prostaglandins via inhibition of cyclo-oxygenase enzyme, but does not inhibit 5-lipo-oxygenase. The inhibition of cyclo-oxygenase does not result in an increase in leukotriene formation. It has short biological half-life (3 to 4 h) and the bioavailability is 90%. Site of absorption of lornoxicam is in the intestine3.
Among the different routes of administration though the oral route continues to be the most preferred one due to various advantages including ease of ingestion, avoidance of pain, versatility and most importantly patient compliance, it still suffers from a drawback especially for pediatric and geriatric patients in the form of difficulty in swallowing.
The two major dosage forms widely used for pediatric and geriatric patients are:
1)Dry syrups
2)Fast dissolving tablets
Dry syrups are highly expensive and unstable hence, to overcome these drawbacks fast dissolving tablets are the better ones for easy administration of drugs to pediatric and geriatric patients.
All most all NSAID’s (Lornoxicam, Meloxicam, Piroxicam etc.,) are intensely bitter drugs, thus in the present study an attempt has been made to mask the Lornoxicam and to formulate into FDT with good mouth feel so as to prepare a “patient- friendly dosage form.”
Methods employed for the development of taste masking are6:

Microencapsulation
Inclusion complexes
Mass extrusion method
Ion exchange resin

The concept of fast dispersing drug delivery system emerged from the desire to provide patient with more conventional means of taking their medication. In some cases such as motion sickness, sudden episodes of allergic attacks or coughing and unavailability of water, swallowing conventional tablets may be difficult. Particularly difficulty is experienced by pediatric and geriatric patients, such problems can be resolved by fast dissolving tablets.
Fast dissolving drug delivery system can be achieved by various methods like direct compression, wet granulation, moulding, spray drying, freeze drying and sublimation. Fast dissolving tablets disintegraterapidly in the saliva without the need for water. Some tablets are designed to disperse in saliva remarkably fast, within a few seconds, and are true fast dispersing tablets. The major advantage of fast dispersing tablet formulation is that it combines the advantage of both liquid and conventional tablet formulations, while also offering advantages over both traditional dosage forms. It provides the convenience of a tablet formulation, while also the ease of swallowing provided by a liquid formulation4.
The major advantages of palatable fast dissolving tablets are5:
Require no water for oral administration, yet dissolve or disintegrate in the mouth in a matter of seconds.
Allow high drug loading.
Masking of bitter taste.
Have a pleasant mouth feel.
Leave minimal or no residue in the mouth after oral administration.
Be portable without fragility concerns.
Exhibit low sensitivity to environmental conditions such as humidity and temperature.
The method which was selected for formulation of palatable fast dissolving tablets is by using ion exchange resins and the resins used are kyron and indion which are used as super disintegrants.Various works have done on sublimation technique, kneading method, polymer carrier system and the present study is an attempt to develop fast dissolving tablets by using ion exchange resins.
6.2 / REVIEW OF LITERATURE:-

Vijay Set al., reviewed that the potent drugs belonging to cardiac analgesics, anti inflammatory, oral vaccines and sex hormones, etc., are bitter in taste, it become necessary to develop such a dosage to patient especially in case of children or geriatrics. To overcome this problem so many techniques are made available to mask the bitter taste of drugs. Commonly used techniques for pharmaceutical dosage form are use of flavours, coating of drug particle with inert materials, by formation of inclusion complexes, by molecular complexes of drug with other chemicals, microencapsulation, multiple emulsions, prodrugs,using liposomes, dispersion coating and ion exchange resin approach6.

Agrawal VA et al., reviewed that taste is an important parameter in administering drugs orally and is a critical factor to be considered while formulating orodispersible, melt in mouth, buccal tablet and other formulations which comes in contact with taste buds. Undesirable and particularly bitter taste is one of the important formulation problems that are encountered with many drugs. Proven methods for bitterness reduction and inhibition have resulted in improved palatability of oral pharmaceuticals. The present review depicts the taste masking techniques like taste masking with flavours, sweeteners, and amino acids, lipophilic vehicles e.g. lipids, lecithin and lecithin-like substances etc and inter coating of drug particles, microencapsulation, inclusion complexes and molecular complexes of drugs with other chemicals, solid dispersions, use of multiple emulsions, liposome’s, prodrugs7.

Mallikarjun S et al., formulated aceclofenac fast dispersible tablets prepared by direct compression method. Effect of superdisintegrants (such as, croscarmellose sodium, sodium starch glycolate, and crospovidone) on wetting time, disintegration time, drug content, in vitro release and stability parameters has been studied. Disintegration time and dissolution parameters (t50% and t80%) decrease with increase in the level of croscarmellose sodium whereas, disintegration time and dissolution parameters increased with increase in the level of sodium starch glycolate in tablets. Stability studies indicated that tablets containing superdisintegrants were sensitive to high humidity conditions8.

Magesh KK et al., worked on to mask the bitter taste of Ondansetron hydrochloride as an orally disintegrating tablet using Indion 294 (ion exchange resin) as a taste masking agent. FT-IR spectrometries were used to investigate the compatibility of drug: resin complex. Super disintegrant like Crosscarmellose sodium, Crospovidone, Indion 234 is used. The results indicated that orally disintegrated tablets of ondansetron hydrochloride containing Indion 234 and Indion 294 provides good taste and better option for quick disintegration and fast release and improved bioavailability9.

Puttewar TY et al., worked on to developdoxilamineorodispersable tablets and the formulations were developed and studied. To prevent bitter taste and unacceptable odour of the drug, the drug was taste masked with weak cation exchange resins like Indion 234, Indion 204 and Indion 414. Among the three resins, one was selected for further studies i.e., Indion 234, because of high drug loading capacity. Drug–resin complex was prepared using batch method and effect of various processing parameters viz. drug–resin ratio, pH, temperature and drug concentration was studied to optimize the loading conditions. Maximum loading was obtained at drug–resin ratio 1:2, pH 5, temperature 500C and drug concentration 4 mg/ml10.

Raghavendra NGRet al., worked to develop fast dissolving tablets of poorly soluble carbamazepine which was formulated using direct compression technique with β-cyclodextrin complexes using various superdisintegrants like Indion-414, croscarmellose sodium,crospovidoneand sodium starch glycolate. The prepared tablets were evaluated for hardness, friability, drug content, weight variation, disintegration time, wetting time, in vitro dissolution studies etc. The different formulations showed disintegration times between the ranges of 26.86 and 58.54 s. Drug release showed time between the range of 4 and 12 min11.

Masareddy RS et al., in their work made an attempt to study two different methods direct compression and sublimation in formulation of mouth dissolving tablets of clozapine. Formulations were prepared using various superdisintegrants and subliming agents. All prepared formulations were evaluated for physico-chemical parameters. The formulations exhibited good disintegration properties with total disintegration time in the range of 25 to 35 s. Comparative evaluation of two methods showed direct compression method is a better alternative to sublimation method as its formulations rapidly disintegrate in oral cavity12.

Patel DM et al., developed fast dissolving tablets of etoricoxib. Granules containing etoricoxib, menthol, crospovidone, aspartame and mannitol were prepared by wet granulation technique. Menthol was sublimed from the granules by exposing the granules to vacuum. The porous granules were then compressed into tablets. The results of multiple regression analysis indicated that for obtaining fast dissolving tablets; optimum amount of menthol and higher percentage of crospovidone should be used13.

Lourenco CF et al., worked on to develop mouth disintegrating tablets of rizatriptan benzoate using superdisintegrants crospovidone,carboxymethylcellulose ,Indion 414 and Indion 234 using the direct compression method. The tablets prepared were evaluated for thickness, uniformity of weight, content uniformity, hardness, friability, wetting time,in vitroandin vivodisintegration time, mouth feel,in vitrodrug release and assay by high performance liquid chromatography. The tablets disintegratedin vitroandin vivowithin 4 to 7 s and 6 to 19 s, respectively. Almost 90% of drug was released from all formulations within 20 min14.

Purnima A et al.,worked onIndion 414, an ion exchange resin, as a new superdisintegrant for pharmaceutical dosage forms. Indion 414 is a pharmaceutical grade weak acid cation exchange resin. Model drugs belonging to various classes were taste masked and formulated into palatable mouth dissolve tablets. Experiments were carried out to evaluate the disintegrant property of Indion 414 by incorporating Indion 414 in fast disintegrating dosage form like mouth dissolve tablets. Indion 414 was compared with the conventional disintegrants to determine its relative efficacy15.

Sradanjali P et al., worked on Metronidazole fast dissolving tablets used in the treatment of motion sickness in adults and children.Theimportant prerequisite for quick relief from motion sickness, is to develop a formulation for this drug which overcomes problems such as difficulty in swallowing, inconvenience in administration while travelling and better compliance. Hence in the present research work mouth dissolving tablets of metronidazole were developed with Superdisintegrants like Crospovidone, Indion 414, L – HPC and pregelatinised starch in various concentrations like 8 % and 10 % w/w by wet granulation method.16

6.3 / OBJECTIVE OF THE STUDY:
The objectives of the present study are following:-
Characterization of drug and excipients for intended formulations.
Compatibility studies for selected drugs and polymers by FTIR, DSC etc.
To mask the bitterness of the drug.
To design and develop fast dissolving tablets by wet granulation method by using ion exchange resins.
To study the comparative effect of ion exchange resins like kyron T-314 and Indion-414.
Characterization offast dissolving tablets for various parameters.
To carry out stability studies on the satisfactory formulation as per ICH guidelines.
7.0
7.1
7.2 / MATERIALS AND METHODS:
SOURCE OF DATA
1)Review of literature from:

Journals – such as
Indian Journal of Pharmaceutical Sciences
International Journey of Pharmacy and Pharmaceutical sciences
International Journal of pharmaceutical research
Asian Journal of Pharmaceutical sciences
Journal of Advanced Pharmaceutical research
Journal of Pharmacy Research
International Journal of Pharma Research and Development
Reference books such as

Ross and Wilson. Anatomy and physiology.9th edition
World Wide Web
J-Gate@Helinet etc

MATERIALS
Drug: Lornoxicam
Disintegrants: kyron T-314,indion etc.
Taste masking agents: Using Flavours,Sweetening agents
Excipients:Aerosil,Mannitol, PVP K-90,Camphoretc.
METHOD OF COLLECTION OF DATA:
To carry out Micromeritic properties likeangle of repose, bulk density, percentage compressibility.
To mask the bitterness of the drug using suitable methodology and evaluate the taste masking.
To study the comparative effect of ion exchange resins like kyron T-314 and Indion-414.
Formulation of fast dissolving tablets by wet granulation method and its evaluation for parameterslike shape, size, hardness, thickness, friability, drug content uniformity, weight variation, uniformity of dispersion, wetting time, in vitro dispersion time, in vitro disintegration time.
In vitro release will be carried out using U.S.P II apparatus then drug content will be evaluated using UV spectrophotometer.
 Stability studies on the optimized formulation as per ICH guidelines.
7.3

7.4 / DOES THE STUDY REQUIRE ANY INVESTIGATION TO BE CONDUCTED ON PATIENT OR OTHER HUMANS OR ANIMALS?
NO
Has ethical clearance been obtained from your institution in case of 7.3?
not APPLIcable
8 / LIST OF REFERENCES:-

Non steroidal anti inflammatory drugs.[online].Available from:

URL: anti inflammatory drugs.

Ross and Wilson. Anatomy and Physiology. 9th edition. Churchill Livingstone; 2003.p.425-26.
Lornoxicam.[online].Available from:

URL:

Paramita Dey, Orodispersible tablets: A new trend sin drug delivery. J Nat Sci Bio Med

2010; 1(1):2-5.

Kuchekar BS, Bhinse SB, Armugam V. Design of fast dissolving tablets. Indian J PharmEdu 2001;35(4):150-52.
Vijay S, Himanshu C. Role of taste and taste masking of bitter drugs in pharmaceutical industries-An overview. Int J Pharm and Pharmsci 2010; 2(4):14-18.
Agrawal VA, Chiddarwar AP, Mahale AM, Wakade RB. Taste abatment techniques to improve palatibilty of oral pharmaceuticals: A Review. Int J Pharm Res and Development 2010; 2(7):1-10.
Mallikarjun S, Prasad DVK, Gupta VRM, B Sa. Development of fast dispersableaceclofenac tablets: Effect of functionality of superdisintegrants. Indian J Pharmsci 2008; 70(2):180
Antaryami J, Magesh K, Ruckmani K. Formulation and evaluation of taste masked orally disintegrating ondansetron hydrochloride tablet. Int J Res PharmSci 2010; 1(3):328-32.
Puttewar TY, Kshirsagar MD, Chandewar AV, Chikhale RV. Formulation and evaluation of orodispersible tablet of taste masked doxylaminesuccinate using ion exchange resin. Jou King Saud Univ 2010; 22:229-40.
Raghvendra NG, Patel T, Gandhi S. Development and evaluation of carbamazepine fast dissolving tablets prepared with a complex by direct compression technique. Asian J Pharm 2009:97-103.
Masareddy RS, Kadia RV, Manvi FV. Development of mouth dissolving tablets of clozapine using two different techniques. Indian J PharmSci 2008; 70(4):526-28.
Patel DM, Patel MM. Optimization of fast dissolving etoricoxib tablets prepared by sublimation technique. Indian J PharmSci 2008; 70(1):71-76.
Lourenco CF, Keny RV, Desouza C. Formulation and evaluation of rizatriptan benzoate mouth disintegrating tablets. Indian J PharmSci 2010; 72(1):79-85.

Purnima A, Namita P, Anita W.Indion 414 as super disintegrant in formulation of mouth dissolve tablets.Indian J PharmSci 2006;68(1):117-9.
Sradhanjali P, Prafulla K D, Guru P R.Development of metronidazole mouth dissolving tablets.J Adv Pharm Res 2010; 1:12-16.

9 / Signature of the candidate:
10 / Remarks of the Guide:
11 / Name and Designation of:

11.1 Institutional Guide: / Dr. RoopaKarki
Professor& HOD
Dept. of Industrial Pharmacy
11.2 Signature:
11.3 Co-Guide:
11.4 Signature:
11.5 Head of the Department: /

Dr.Roopakarki

Professor & HOD
Dept. of Industrial Pharmacy
11.6 Signature
12 / 12.1 Remarks of the Principal
12.2 Signature /

Dr. Goli Divakar

Principal

ACHARYA & B.M.REDDY COLLEGE OF PHARMACY,
SOLDEVANAHALLI,
HESARAGHATTA MAIN ROAD,
BANGALORE-90.