FORMULATION AND EVALUATION OF PALATABLE FAST DISSOLVING
TABLETS OF LORNOXICAM
M. Pharm dissertation protocol submitted to
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore – 560 041
By
MS. BANDI MOUNICA B.pharm
Under the Guidance of
Mr. RAVI SARMA M.pharm
Asst. Professor
Department of Industrial Pharmacy
Acharya & B.M.Reddy College of Pharmacy
Soldevanahalli, Chikkabanavara (Post)
Hesarghatta main road, Bangalore – 560 090
2010 – 2011
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE.
ANNNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1 / Name and address of candidate / Bandi Mounica,D/o B.satyanarayana Rao,
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 LORNOXICAM6
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 are:
· Microencapsulation/
· Inclusion complexes/
· Ion exchange resin/
· Mass extrusion method6.
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 disintegrate rapidly 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 are:
Ø Require no water for oral administration, yet dissolve or disintegrate in the mouth in a matter of seconds.
Ø Allow high drug loading.
Ø Masking of bitter taste
Ø Have a pleasant mouth feel.
Ø Leave minimal or no residue in the mouth after oral administration.
Ø Be portable without fragility concerns.
Ø Exhibit low sensitivity to environmental conditions such as humidity and temperature.
Ø Allows the manufacturing of tablets using conventional processing and packaging equipment at low costs5.
6.2
/ REVIEW OF LITERATURE:-
· Sharma V et al., reviewed that as most of the potent drugs belonging to cardiac analgesics, anti inflammatory, anti tubercular, antihalmentics , antibacterial ,anticoagulants, anti epileptics, antimalarials, antineoplastics, anti thyroids, antiprotozoal, diuretics, histamine receptor antagonists, nutritional agents, opioid analgesics, oral vaccines and sex hormones, etc., are bitter in taste, it becomes necessary to develop such a dosage for that must be acceptable in taste 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 that are adopted for large scale production of 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.
· Magesh Kumar K 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 are used. The granules were evaluated for pre-compression parameters like angle of repose, bulk density, tapped density, compressibility index and post compression parameters were evaluated. 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 bioavailability7.
· Anand V et al., worked on to develop taste-masked orally disintegrating tablets (ODTs) of prednisolone (PDL) by incorporation of microspheres in the tablets for use in specific populations viz. pediatrics, geriatrics and patients experiencing difficulty in swallowing. By using the method of microspheres containing PDL were prepared by the solvent evaporation method using acetone as solvent for pH-sensitive polymer and light liquid paraffin as the encapsulating medium. Taste evaluation studies confirmed that microspheres of PDL having a drug to polymer ratio of 1: 10 are tasteless and these were further used for formulation into ODTs8.
· Puttewar TY et al., worked on to develop doxilamine orodispersable tablets with considerable increase in drug release as compared to marketed formulations. 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/ml. A successful taste masking of resinate was confirmed by time intensity method and also by taking drug release in 0.01 N hydrochloric acid and in simulated salivary fluid. The data obtained of post-compression parameters such as weight variation, hardness, friability, wetting time, water absorption ratio, content uniformity, disintegration time and dissolution and was found superior over conventional formulation9.
· 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. Administration of bitter drugs orally with acceptable level of palatability is a key issue for health care providers. Proven methods for bitterness reduction and inhibition have resulted in improved palatability of oral pharmaceuticals. The problem of bitter and obnoxious taste of drug in pediatric and geriatric formulations is a challenge to the pharmacist in the present scenario. 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, prodrugs10.
· Raghavendra rao N G et 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,
crospovidone and 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.
· Shailesh S et al., developed fast dissolving tablets of promethazine theoclate which were prepared by direct compression method after incorporating super disintegrants ac-di-sol and sodium starch glycolate and crospovidone in different concentrations and are assessed for their critical concentration levels and efficiencies. Different types of evaluation parameter for tablet were used. Tablets containing ac-di-sol salt showed superior organoleptic properties along with excellent in vivo and in-vitro dispersion time and drug release as compare to other formulations12.
· Senthil KR et al., worked on to develop fast dissolving tablets of terbutaline sulfate were prepared by the direct compression method after incorporating superdisintegrants such as Explotab, Ac-di-sol and Polyplasdone XL in different concentrations. The prepared tablets were evaluated for weight variation, thickness, hardness, friability, wetting time, drug content, water absorption ratio, in vitro dispersion time, in vitro disintegration time and in vitro drug release. Among all the formulation which is containing 5% w/w concentration of polyplasdone XL was considered to be the best formulation which releases upto 99.33% of the drug in 10 min13.
· Mallikarjun S et al., formulated aceclofenac fast dispersible tablets which have been 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. However, the disintegration time values did not reflect in the dissolution parameter values of crospovidone tablets and release was dependent on the aggregate size in the dissolution medium. Stability studies indicated that tablets containing superdisintegrants were sensitive to high humidity conditions14.
· 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 cavity15.
· Swamy PV et al., developed orodispersible tablets of pheniramine maleate by effervescent method. In the effervescent method, mixture of sodium bicarbonate and tartaric acid (each of 12% w/w concentration) were used along with super disintegrants, i.e., pregelatinized starch, sodium starch glycolate, croscarmellose sodium and crospovidone. Based on in vitro dispersion time (approximately 60 s), three formulations were tested for in vitro drug release pattern (in pH 6.8 phosphate buffer), short-term stability (at 40±2°/75±5% RH for 3 months) and drug-excipient interaction (IR spectroscopy). Among three promising formulations, formulation containing 4% w/w crospovidone and mixture of sodium bicarbonate and tartaric acid (each of 12% w/w) emerged as the overall best formulation (t70% = 1.65 min)16.
· 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. A 32 full factorial design was applied to investigate the combined effect of 2 formulation variables: amount of menthol and crospovidone. The results of multiple regression analysis indicated that for obtaining fast dissolving tablets; optimum amount of menthol and higher percentage of crospovidone should be used17.