Download design and development of lornoxicam fast dissolving tablets by

DESIGN AND DEVELOPMENT OF LORNOXICAM FAST
DISSOLVING TABLETS BY DIFFERENT TECHNIQUES
M.PHARM DISSERTATION PROTOCOL
Submitted to
Rajiv Gandhi University of Health Sciences
Bangalore, Karnataka
By
PARIKH BHAVIK A.
B.Pharm
Under the Guidance
of
Prof. Sanjeev L. Gupta
M.Pharm (Ph.D)
DEPARTMENT OF PHARMACEUTICS
R.M.E.S’s COLLEGE OF PHARMACY,
GULBARGA-585102
2009-2010
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA.
CURRICULUM DEVELOPMENT CELL
CONFORMATION FOR REGISTRATION OF
SUBJECT FOR DISSERTATION
Registration No.
:
Name of the Candidate
:
Parikh Bhavik A.
Address
:
R.M.E.S’s College of Pharmacy
Gulbarga, Karnataka.
Name of the Institution
:
R.M.E.S’s College of Pharmacy
Gulbarga, Karnataka.
Course of Study and Subject
:
M.Pharma in Pharmaceutics
Date of Admission to the Course :
26th October 2009
Title of the Topic
Design and development of Lornoxicam fast
:
dissolving tablets by different techniques.
Brief resume of the intended work :
Enclosed
Signature of the student
:
Guide Name
:
Prof. Sanjeev L.Gupta M.Pharm(Ph.D)
Remarks of the Guide
:
Recommended for approval
Signature of the Guide
:
Co-Guide Name
:
Signature of the Co-Guide
:
HOD Name
:
Signature of the HOD
:
Director/Principal Name
:
Prof. Kishoresingh k.chatrapathi M.Pharm Ph.d
Mobile No
:
+919880200905
Director/Principal E-mail
:
[email protected]
Remarks of Director/principal
:
Recommended for approval
Director/Principal Signature
:
Mr.Upendra Kulkarni M.Pharm(Ph.D)
Prof. Hariprasanna R. C. M.Pharm(Ph.D)
Rajiv Gandhi University of Health Sciences
Bangalore, Karnataka
ANNEXURE - II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1.
Name and Address of the candidate
Parikh Bhavik A.,
B-19, Pooja Park Society,
Zadeshwari GNFC bypass Road,
Near GNFC Township,
Bharuch,
Gujarat.
2.
Name of the Institution
R.M.E.S’s College of Pharmacy, Gulbarga,
Karnataka-585102
3.
Course of study and subject
Master of Pharmacy in Pharmaceutics
4.
Date of admission to course
26th October 2009
5.
Title of the topic
Design and development of Lornoxicam fast
dissolving tablets by different techniques.
6.
Brief resume of the intended work
6.1 Need of the study
The oral route of administration still continues to be the most preferred route due to
its manifold advantages including ease of ingestion, pain avoidance, versatality, accurate
dosage, self-medication and most importantly patient compliance.1-2 It has been shown that
the dissolution rate of pure drug can be altered significantly by the proper selection of
formulation component as well as processing method.3 Reports related to effect of
formulation excipients like diluants4, disintegrants5, surfactant6, granulating agents7 and
binders8 are available. In other set of works effect of processing factors such as method of
granulation9 on the dissolution rate have been reported. Ho and Hersey10, have introduced
a novel method of granulation based on the agglomeration due to prolonged grinding to
improve the dissolution rate of paracetamol from tablets.
The oral fast-dissolving dosage forms, also known as fast-melt, fast disintegrating
dosage forms, are a relatively novel dosage technology that involves rapid disintegration or
dissolution of the dosage forms, into a solution or suspension in the mouth without need for
water.11-15 The dosage form begins to disintegrate immediately after coming into contact
with saliva, with complete disintegration normally occurring within 30-50s after
administarion.16 The solution containing active ingredients is swallowed, and the active
ingredients are than absorbed through the gastrointestinal epithelium to reach the target
and produce the desired effect.17
Fast dissolving tablets (FDT) are designed for the purpose of improving patient
acceptance and compliance. A survey of 6158 GP patients conducted in Norway indicated
that approximately 26% of all patients do not take their prescribed medication as they
encountered problems when swallowing conventional tablets. Often, the main complaints
are the size, surface and taste of the tablets. 18-19 FDT help to overcome some of these
problems: the rapid disintegration of the tablet into a solution containing the drug enables
those who find difficulty in or experience discomfort when swallowing, to have a more
patient friendly experience.17 Target group for FDT are wide-ranging as people of all ages
can experience difficulty in conventional tablets and capsules. This includes children and
elderly who either experience difficulty and cannot swallow or have not learnt to swallow
the conventional solid dosage forms. In addition, institutionalized psychiatric patient as well
as hospitalized or bedridden patients suffering from a variety of disorders such as stroke,
thyroid disorder, Parkinson’s disease and other neurological disorders also find difficulty in
swallowing and require fast-melt tablets because of their physical condition. The
convention and the ease of using FDTs is also important to normal consumers, with some
adults preferring this dosage forms as they are easy to handle and swallow, can be taken
without water and have a rapid onset of action.20 For example, patients with a limited
access to water would also find such FDTs extremely beneficial.17
Lornoxicam is a non-steroidal anti-inflammatory drug with extremely potent antiinflammatory and analgesic activity. It is widely used for the symptomatic treatment of pain
and inflammation in patients with rheumatoid arthritis and osteoarthritis. Moreever it
showed grate efficacy in various clinical trials in the management of perioperative and
postoperative pain associated with gynecological, orthopedic, abdominal and dental
surgeries. Lornoxicam shows distinct pH-dependent solubility characterized by very poor
solubility in acidic condition present in the stomach.21-24
Therefore, the main objective of the present investigation is to fabricate and
optimize the fast-dissolving tablets containing Lornoxicam by different techniques.
6.2
Review of Literature
1) J.J Zhang et al.25 prepared Lornoxicam solid dispersion systems with polyvinyl pyrrolidone
K30(PVP), Gelucire 44/14(GLC) and poloxamer188 (PXM) by solvent method at different
weight ratios, the correspomding physical mixture were used as control group. The relative
potency of carrier for dissolution improvement might be ranked as PXM> PVP>GLC. The
type of carrier and drug-carrier ratio had great effect on the characterization of dissolution
and heat enthalpy of Lornoxicam solid dispersion.
2) Gohel et al.26 prepared mouth dissolving tablets for nimesulide by preparing granules
containing nimesulide, camphor, crospovidone and lactose and then camphor was
sublimed from granules, alternatively, first tablets were prepared and then camphor was
sublimed by vacuum. Sublimation of camphor from tablets resulted in superior tablets as
compared with tablets prepared from granules that were exposed to vacuum.
3) Lalla et al.27
-cyclodextrin using
ball milling technique and evaluated using DSC. Fast dissolving tablets composition with
25mg equivalent rofecoxib showed complete release of rofecoxib in 12 minutes as
compared to 20% drug released form the conventional release marketed tablets during the
same period of time.
4) Mahaparale et al.28 prepared solid dispersion of meloxicam by solvent evaporation method
with polyvinyl pyrrolidone (PVP), polyethylene glycol 6000 (PEG 6000) and polyethylene
glycol 4000 (PEG 4000) dissolution study was carried out for all solid dispersion. All solid
dispersion of Meloxicam showed higher solubility and faster dissolution then pure drug
alone. Meloxicam: PVP (1:9) ratio showed highest solubility and faster dissolution than any
other solid dispersion.
5) N. G. Raghavendra et al.29 prepared fast- dissolving tablets of carbamazepine by solid
dispersion method. The formulations prepared with mannintol solid dispersion were
showed disintegration time between the ranges of 12.83 – 16.79 sec and drug release
showed between the range of 8 – 10 minutes. However the formulations prepared with
PEG 6000 solid dispersion did not disintegrate in specified limit of time for fast-dissolving
tablets.
6) Desai et al.30 prepared orodissolving tablets of promethazine hydrochloride using
superdisintegrants, sodium starch glycolate and croscarmellose sodium by direct
compression method. The formulations containing 4% of sodium starch glycolate and 1-3%
of croscarmellose sodium were found to give the best results. Thus, the tablets apart from
fulfilling all official and other specifications, exhibited higher rate of release.
7) Babu et al.31 prepared solid dispersion of piroxicam in five super disintegrants namely
primogel, microcrystalline cellulose, crospovidone, pregeletinized starch, croscarmellose
sodium and with water soluble carriers polyvinyl pyrrolidone and polyethylene glycol. Solid
dispersions of piroxicam in super disintegrants gave a marked enhancement in its
dissolution rate and dissolution efficiency. Solid dispersion in super disintegrants could be
used as an effective and efficient technique for enhancing the dissolution rate of piroxicam
a poorly soluble drug.
8) Patel et al32 formulated tablets of Piroxicam with PVP K30 and sodium lauryl sulphate with
a view to increase its water solubility. Sodium lauryl sulphate is used in solid dispersion
with PVP K30 by solvent evaporation method. This solid dispersion is made to tablets by
using different disintegrating agents like sodium starch glycolate and crospovidone. 3 2
factorial designs were applied for the study and they found increase in dissolution with the
superdisintegrants concentration. They found no significant change after four weeks kept at
45oc.
9) Bolhuis et al.33 prepared the solid dispersion by surface depositions of the poorly soluble
and hydrophobic drug on the surface of the hydrophilic and highly swelling
superdisintegrants. They found that wet granulation of drug with sodium starch glycolate
show a large increase in the solubility of the drug. The granules containing too high
concentration of superdisintegrants showed low drug release from the tablets. Thus
viscous layer of superdisintegrants in the granules describes effect during the dissolution
process.
10) Chowdary and Rao34 prepared solid dispersion of itraconazole in lactose, microcrystalline
celluclose and three superdisintegrants (Primogel, Kollidon CL, and Ac-Di-Sol) and their
formulations into tablets were investigated with an objective of enhancing the dissolution
rate of itraconazole from tablet formulations. A marked enhancement in the order of the
excipients to enhance the dissolution rate was Ac-Di-Sol.
11) Shu et al.35 formulated rapid oral disintegration tablets by direct compression using coground mixture of D-mannitol and crospovidone. The tablets manufacturing from a physical
mixture of 30% (w/v) co-ground mixture of D-mannitol and crospovidone (mixed ratio 9:1)
with 65.5% (w/v) of non-ground mannitol, 4% (w/v) of crospovidone, and 0.5% (w/v) of
magnesium sterate had good properties for rapidly disintegrating tablets in the oral cavity.
The presumed that crospovidone acted as a grinding assistant for D-mannitol in the cogrinding process, enhancing the hardness of tablets by increasing the contact area among
powder particles.
12) Riikka Laitinen et al.36 prepared fast-dissolving particles of poorly soluble perphenazine
drug. In the study the dissolution rate of a poorly soluble drug was improved by solid
dispersion technique to permit its usage in intraoral formulations. PVP K30 and PEG 8000
were selected for carriers according to solubility parameter approach and their 5/1, 1/5 and
1/20 mixtures with perphenazine were prepared by freeze drying from 0.1N HCl solution.
The dissolution rate of PPZ was improved with all drug/polymer mixture ratios compared to
crystalline or micronized PPZ. A major dissolution rate improvement was seen by 1/5
PPZ/PEG formulations.
6.3
Objectives of the study
The present research study is planed with the following objectives.
1) To fabricate fast-dissolving tablets of Lornoxicam by different techniques like solid
dispersion method, by using natural and synthetic superdisintegrants and by sublimation
technique, etc.
2) To evaluate the formulations with respect to various physical parameters.
3) To evaluate the formulations with respect to content uniformity, in vitro release studies, etc.
4) To characterize the formulation by instrumental methods like FTIR, DSC and XRD, etc.
5) To perform the stability studies on promised formulations.
7
Material and Method
7.1 Source of data
Primary data: This data will be collected by conducting laboratory experiment and
recording the observation.
Secondary data: This will be collected from various journals and text book
7.2 Methods of Collection of data
The data for the study is planned to collect from the laboratories based on experiment
which include the following:
-Formulation and development of fast-dissolving tablets containing Lornoxicam.
-Evaluation fast dissolving tablets with respect to drug content determination and in vitro
release study.
-Evaluation of fast dissolving tablets with respect to some physical parameter
7.3
Does the study require any investigation to be conducted on patients or other humans
Or animals? If so, please describe briefly.
Not under the plan of the work
7.4
Has ethical clearance been obtained from your institution in case of 7.3
NOT APPLICABLE
8
List of References
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2001; 35(4): 150-2.
2) Chien YW. Novel drug delivery systems. 2nd Ed. New York: Marcel Dekker; 1992.
3) Abdou HM. (Ed.). Factors affecting the rate of dissolution of solid dosage forms. In;
Dissolution, bioavailability and bioequivalence. Pp 73-105. Mack publishing
company eastonpennsulvanio.
4)
-lactose, PVP K12 and PVP K90 as
excipients to prepare Piroxicam granules using two wet granulation techniques. Eur J
Pharm Biopharm. 2003; (56): 479-87.
5) Solvang S, Finhold P. Phenobarbital tablets by wet and dry granulation methods. J Pharm
Acta Helv. 1970; ibid 59: 49.
6) Chen L R, Wesley JA, Bhattachar S, Ruiz B, Bahash K, Babu S R. Dissolution behavior of
a poorly water soluble compound in the presence of Tween 80. Pharm Res. 2003; 20(5):
797-801.
7) Marlowe E, Shagraw R. Sodium salicylate tablet using wet granulation and direct
compression methods. J Pharm Sci. 1967; 56: 498.
8) Chebli C, Cartilier L. Cross-linked cellulose as a tablet excipient: A binding/disintegrating
agent. Ind J Pharm. 1998: 171: 101-10.
9) Sanderson I M, Kennerley J W, Parr G D. An evaluation of the relative importance of
formulation and process variables using factorial design. Pharmacol. 1984; 36(12): 78995.
10) Ho T, Hersay J. Compatibility of granules prepared by a novel method of granulation and
their dissolution. J Pharm Pharmacol. 1980; 32(3): 160-6.
11) M. Chiper, R. Bodmeier, Modified conventional hard gelatin capsules as fast disintegrating
dosage form in the oral cavity, Eur. J. Pharm Biopharm. 62(2006) 178-184.
12) T. Mizumoto, Y. Masuda, T. Yamamoto, E. Yonemochi, K. Terada, Formulation design of a
novel fast disintegrating tablet, Int. J. Pharm 306(2005) 83-90.
13) H. Seager, Drug delivery products and the Zydis fast dissolving dosage form, J. Pharm.
Pharmacol. 50 (1998).
14) S.V. Sastry, J.R. Nyshadham, J.A. Fix, Recent technological advance in oral drug delivery:
A review, Pharm. Sci. Technol. Today 3 (4)(2000) 138-145.
15) EU Pharmacopoeia, Published by the Directorate for the Quality of Medicines of the
Council of Europe (EDQM), second ed., Strasbourg, France, 2002a.
16) L.Dobetti, Fast-melting tabets: Development and technologies, Pharm. Technol. N. Am.
Suppl. (2001) 44-50.
17) Rahul Chandrasekhar, Zahra Hassan, Farhan AlHusban, Alan M. Smith, Afzal R.
Mohammed, The role of formulation excipients in the development of lyophilized fastdisintegrating tablets. European Journal of Pharmaceutics and Biopharmaceutics 72
(2009) 119-129.
18) O.Anderson, O.K. Zweidorff, T. Hjelde, E.A. Roaland, Problems with swallowing tablets: a
questionnaire study from general practice, Tidsskr. Nor. Loegeforen 20 (1995) 947-949.
19) H.W. Frijlink, Benefits of different drug formulations in psychopharmacology, Eur.
Neuropsychopharmacol.13 (suppl. 3) (2003) S77-S84.
20) S.H. Jeong, K. Park, Development of sustained release fast-disintegrating tablets using
various polymer-coated ion-exchange resin complexes, Int. J. Pharm. 353 (1-2) (2008)
195-204.
21) Homdrum EM, Likar R, Nell G. Xefo Rapid: a novel effective tool for pain treatment. Eur
Surg. 2006; 38: 342-52.
22) Kidd B, Frenzel W. A multicenter, randomized, double blind study comparing Lornoxicam
with Diclofenac in osteoarthritis. J Rheumatol. 1996; 23: 1605-11.
23) Balfour JA, Fitton A, Barradell LB, Lornoxicam, A review of its pharmacology and
therapeutics potential in the management of and inflammatory conditions. Drugs. 1996;
51: 639-57.
24) Skjodt NM, Davies NM, Clinical pharmacokinetics of Lornoxicam. A short half-life Oxicam.
Clin. Pharmacokinet. 1998; 34: 421-8.
25) http://www.aapsj.org/abstracts/Am_2003/AAPS2003-002004.pdf
26) Gohel MC, Patel MM, Amin AF, Agrawal R, Dave R, Bariya N. Formulation design and
optimization of mouth dissolving tablets of Nimesulide using vacuum drying technique.
AAPS PharmSciTech 2004: 5(3): Article 36.
27) Lalla JK, Mamania HM. Fast dissolving Rofecoxib tablets. Indian J Pharm Sci 2004 May;
66(4): 350-3.
28) Mahaparale P R, Gudsoorkar VR, Gajeli GB, Kuchekar BS. Studies on solid dispersion of
Meloxicam. Indian J Pharm Sci 2006; 40(3) 172-4.
29) N. G. Raghavendra Rao, Tarun Patel, Upendra Kulkarni. Formulation and evaluation of fast
dissolving tablets of Carbamazepine by Solid dispersion method. IJPT\March 2010\Vol. 1\
Issue No.2\23-37.
30) Desai SA, Khavade SV, Petkar KC, Kuchekar BS. Orodissolving tablets of Promethazine
Hydrochloride. Indian J Pharm Sci 2006; 40(3) 172-4.
31) Srinivas Babu P, Ramu A, Sasidhar R, Vidhyadhara. Enhancement of dissolution rate of
Piroxicam by solid dispersion using newer carriers. The Pharma review 2007; 163-6.
32) Patel DM, Shah RR, Jogani PD. Tablets Formulation of Piroxicam containing PVP K30 and
SLS. Indian J. Pharm Sci 2004 Jan; 66 (1) 49-55.
33) Bolhuis GK, Zuurman K, Wierik GHP. Improvement of dissolution of poorly soluble drugs
by solid deposition on a superdisintegrant. II. The choice of superdisintegrants and effect of
granulation. Eur J Pharm Sci 1997; 5(1-2): 63-9.
34) Chowdary KPR, Rao SS. Investigation of Dissolution enhancement of Itraconazole by solid
dispersion in superdisintegrants. Drug Dev Ind Pharm 2000 Nov; 26(11) 1207-11.
35) Shu T, Suzuki H, Hirokana K, Ito K. Studies of rapidly disintegrating tablets in the oral
cavity using co-ground mixtures of Mannitol with Crospovidone. Chem Pharm Bull 2002;
50(2): 193-8.
36) Riikka Laitinen, Eero Suihko, Kaisa Toukola, Mikko Bjorkqvist, Joakim Riikonen, Vesa
Pekka Lehto, Kristiina Jarvinen, Jarkko Ketolainen. Intraorally fast-dissolving particles of a
poorly soluble drug: Preparation and in vitro characterization. European Journal of
Pharmaceutics and Biopharmaceutics 71 (2009) 271-281.
9.
Signature of candidate
10. Remark of the guide
11
The above information and literature has been
extensively investigated, verified and was found
to be correct. The present study will be carried
out under my supervision and guidance.
Name & Designation of
11.1 Guide
Prof. Sanjeev L.Gupta
M.Pharm,( Ph.D)
Professor
Department of Pharmaceutics
R.M.E.S.’s College of Pharmacy,
Gulbarga-585102.
11.2 Signature
11.3 Co-Guide (if any)
Mr.Upendra Kulkarni,
M.Pharm,(Ph.D)
Lecturer,
Department of Pharmaceutics
R.M.E.S.’s College of Pharmacy,
Gulbarga-585102.
11.4 Signature
11.5 Head of the Department
Prof. Hariprasanna R. C.
M.Pharm,(Ph.D)
Professor & HOD
Department of Pharmaceutics
R.M.E.S.’s College of Pharmacy, Gulbarga.
11.6 Signature
12
12.1 Remark of the Director / The above mentioned information is correct
principal
and I recommend the same for approval.
12.2 Signature
Prof. Kishoresingh K.Chatrapathi
M.Pharm, Ph.D
Director/Principal
R.M.E.S’s College OF Pharmacy,Gulbarga