FORMULATION AND EVALUATION OF FAST DISINTEGRATING TABLETS OF OXCARBAZEPINE
M.Pharm. Dissertation Protocol
Submitted to the
Rajiv Gandhi University of Health Sciences, Karnataka.
Bangalore.
By
SONI ASHISHKUMAR MAHENDRAKUMAR
B.Pharm.
Under the Guidance of
P. RAVI PRAKASH,
Assistant Professor,
Dept. of Pharmaceutics
DEPARTMENT OF PHARMACEUTICS
N.E.T. PHARMACY COLLEGE, RAICHUR
2007
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1 / Name of candidate and address (In Block Letters) / SONI ASHISHKUMAR MAHENDRAKUMARS/O SONI MAHENDRAKUMAR MANEKLALB/1/117,Nar-narayana Bunglows and society,Bholav, P.O.-Narmadanagar
Bharuch-392001
GUJARAT.
2 / Name of the Institute / N.E.T.PHARMACY COLLEGE,
RAICHUR.
3 / Course of study and subject: / M.PHARM. PHARMACEUTICS.
4 / Date of admission of course: / 02-05-2007
5 / Title of the topic:
FORMULATION AND EVALUATION OF FAST DISINTEGRATING TABLETS OF OXCARBAZEPINE.
6 / Brief Resume of this intended work:
6.1 Need for the study Enclosure-I
6.2 Review of Literature Enclosure-II
6.3 Objectives of study Enclosure-III
7 / Materials and Methods:
7.1 Source of data Enclosure-IV
7.2 Method of collection of data (Including Sampling procedure, if any)
Enclosure-V
7.3 Does the study require any investigation or interventions to be conducted on patients of humans or animals ? If so, please describe briefly.
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7.4 Has ethical clearance been obtained from your institution in case of 7.3 ?
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8 / List of References Enclosure-VI
9 / Signature of the candidate
10 / Remarks of the Guide / The proposed work can be carried out in the laboratory
11 / Name and designation of
(in block letters)
11.1 Guide
11.2 Signature / P. RAVI PRAKASH,
Assistant Professor,
Dept. of Pharmaceutics,
N.E.T.Pharmacy College,
Raichur-584103.
11.3 Co-Guide (if any)
11.4 Signature / ------
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11.5 Head of Department
11.6 Signature / PROF. H.DODDAYYA,
Dept. of Pharmaceutics,
N.E.T.Pharmacy College,
Raichur-584103.
12 / 12.1 Remarks of the Chairman and Principal
12.2 Signature / PROF. H.DODDAYYA,
Principal,
N.E.T.Pharmacy College,
Raichur-584103.
Enclosure-I
6) Brief resume of the intended work.
6.1) Need for the study:
The oral route of administration still continues to be the most preferred route due to it’s manifold advantages including ease of ingestion, pain avoidance, versatility and most importantly patient compliance.1 Oral solid dosage forms are popular because of ease of administration, accurate dosage, self medication, pain avoidance and most importantly patient compliance.2 Tablets hold premier position among all dosage forms.3 Among the pharmaceutical dosage forms, the conventional tablet seems to be most popular, because of its ease of transportability and comparatively lower manufacturing cost.4
There are two different types of dispersible tablets which have to be distinguished: one dosage form disintegrates instantaneously in the mouth to be swallowed without need of drinking water. 5,6,7 While the other tablet formulation can readily be dispersed in water to form a dispersion, easy to ingest by the patient.8,9 Faster the drug in solution, quicker the absorption and onset of clinical effect, because, some drugs are absorbed from the mouth, pharynx and oesophagus as the saliva passes down into the stomach.10 In such cases, bioavailability of drug is significantly greater than those observed from conventional tablet dosage form.11 Thus, fast dissolving tablets have the advantages of both solid and liquid dosage forms.12 The target population for these new fast dissolving/disintegrating dosage forms have generally been pediatric, geriatric, and bedridden or developmentally disabeled patients. Patients with persistent nausea, who are travelling or who have little or no access of water are also good candidate for fast dissolving/disintegrating tablets. 6
Oxcarbazepine, a keto analogue of carbamazepine has been registered by US FDA in Dec 2001.13 It is used as add on or first line treatment in patients with generalized tonic clonic seizures and partial seizures with or without secondary generalization in adults and as an adjunctive in children.14 Its insolubility in water and blend taste makes it an ideal candidate for fast disintegrating tablets with regards to palatability. Since epileptic patients have to strictly follow the dosage regimen for preventing sub therapeutic concentration. Fast dissolving/ disintegrating tablets will avoid missing out of dose even during travelling or other situation where there is no access to water. The poor dissolution of relatively insoluble drugs has been a problem in the formulation of oral dosage forms. This limits the aspects such as absorption and bioavailability.15
Hence in the present work attempt will be made to develop and evaluate fast disintegrating formulation of oxcarbazepine.
Enclosure-II
6.2) Review of literature:
1) Kuchekar BS et al. (2006)1 prepared orodissolving tablets of promethazine-HCl using superdisintegrants like sodium starch glycolate and croscarmellose sodium by direct compression method and reported that formulation containing 4% of sodium starch glycolate and 1-3% of croscarmellose sodium were found to give the best results.
2) Sreenivas SA et al. (2006)11 prepared ondansetron hydrochloride mouth disintegrating tablets using various disintegrants like crospovidone, croscarmellose sodium, pregelatinized starch, sodium starch glycolate and low-substituted hydroxyl propyl cellulose (L-HPC) in 5% and 10% concentrations and by direct compression, and reported that tablets containing 10% disintegrant concentration of crospovidone and croscarmellose sodium were best for ondansetron hydrochloride mouth disintegrating tablets.
3) Lalla JK et al. (2004)16 prepared inclusion complex of rofecoxib, an NSAID with β-cyclodextrin using ball milling technique and evaluated using DSC. Fast dissolving tablet composition with 25 mg equivalent rofecoxib showed complete release of rofecoxib in 12 minutes as compared to 20% drug release from the conventional release marketed tablets during the same period.
4) Nayak SM et al. (2004)17 reported the design and optimization of fast dissolving tablets for promethazine theoclate. The tablets were prepared using effervescent melt, superdisintegrant addition and melt technologies. They reported that the tablets from the effervescent melt and superdisintegrant addition technique released 92% and 89% of the drug at the end of 10 mins respectively.
5) Toshihiro Shimizu et al. (2003)18 prepared lansoprazole fast disintegrating tablets. Lansoprazole enteric coated microgranules prepared with micro crystalline cellulose, low substituted hydroxyl propyl cellulose (L-HPC-33), cross povidone as binder and disintegrants were prepared by wet granulation method and compressed into tablets with a rotary tablet press. Low substituted hydroxyl propyl cellulose (L-HPC-33) is reported to be useful as a binder and disintegrants in a rapidly disintegrating tablet.
6) Pandey S et al. (2003)19 reported the optimization of fast dissolving dosage form of diclofenac sodium by rapidly disintegrating agents such as crosslinked carboxy methyl cellulose, sodium starch glycolate and crospovidone. Tablets containing crosslinked carboxy methyl cellulose showed better disintegrating character along with rapid release. (90% drug release in 10 minutes)
7) Chowdary KPR et al. (2000)20 formulated dispersible tablets of ibuprofen employing potato starch, primogel, microcrystallinecellulose(MCC) and pregelatinised starch (PGS) and reported that tablets formulated employing primogel as internal & external disintegrant and tablets formulated employing potato starch as internal disintegrents and primogel and PGS as external disintegrents fulfilled all the official and other requirements of dispersible tablets.
8) Chowdary KPR et al. (1998)21 formulated dispersible tablets of norfloxacine, paracetamol and piroxicam with pre-gelatinized starch as disintegrant. A concentration of 10-20% of pre-gelatinized starch in formulation is reported to be optimum for formulation of dispersible tablet.
Enclosure-III
6.3) Objectives of the study:
The present study is planned with the following objectives:
1) To prepare the fast disintegrating tablet of oxcarbazepine.
2) To evaluate the formulations with respect to various physical parameters (weight variation, hardness, friability, etc.)
3) To evaluate the tablets with respect to content uniformity, in vitro disintegration time and in vitro dissolution rate studies.
Enclosure-IV
7) Materials and Methods:
7.1) Source of data:
Primary data: This data will be collected by conducting laboratory experiments and recording the observation.
Secondary data: This will be collected from various journals and textbooks.
Enclosure-V
7.2) Method of collection of data:
The data for the study is planned to collect from the laboratory based experiments, which include the following –
Preparation of fast disintegrating tablets of oxcarbazepine.
Evaluation of fast disintegrating tablets with respect to drug content determination, in vitro disintegration time, in vitro dissolution rate studies etc.
Evaluation of fast disintegrating tablets with respect to some physical parameters (weight variation, hardness, friability etc.)
Enclosure-VI
8) List of references:
1) Kuchekar BS; Bhise SB; Arumugam V. Design of fast dissolving tablets. Ind J Pharm Edu 2001; 35(4): 150-152.
2) Chien YW. Novel drug delivery systems. 2nd ed. New York: Marcel Dekker; 1992: 139.
3) Patel DM; Patel NM; Shah RR; Jogani PD; Balapatel AI. Studies in formulation of orodispersible tablets of rofecoxib. Ind J Pharm Sci 2004; 66(5): 621-625.
4) Reddy LH; Ghosh B; Rajneesh. Fast dissolving drug delivery systems: A review of the literature. Ind J Pharm Sci 2002; 64(4): 331-336.
5) Bi Y; Sunada H; Yonezawa Y; Danjo K; Otsuka A; Lida K. Preparation and evaluation of a compressed tablet rapidly disintegrating in oral cavity. Chem Pharm Bull 1996; 44: 2121-2127.
6) Chang RK; Guo X; Burnside BA; Couch RA. Fast dissolving tablets. Pharm Technol Eur 2000; 12(6): 52-58.
7) Watanabe Y; Koizume K; Zama Y; Kiriyama M; Matsumoto Y; Matsumoto M. New compressed tablet rapidly disintegrating in saliva in the mouth using crystalline cellulose and a disintegrant. Biol Pharm Bull 1995; 18: 1308-1310.
8) Martin TP; Hayes P; Collins DM. Tablet dispersion as an alternative to formulation of oral liquid dosage form. Aust J Hosp Pharm 1993; 23: 378-381.
9) Schiermeier S; Schmidt PC. Fast dispersible ibuprofen tablets. Eur J Pharm Sci 2002; 15: 295-305.
10) Amita N; Kandarapu R; Garg S. An update on taste masking technologies for oral pharmaceuticals. Ind J Pharm Sci 2002; 64(1): 10-17.
11) Sreenivas SA; Dandagi PM; Gadad AP; Godbole AM; Hiremath SP; Mastiholimath VS. Orodispersible tablets: New-fangled drug delivery system-A review. Ind J Pharm Edu 2005; 39(4): 177-181.
12) Bhushan SY; Sambhaji SP; Anant RP; Mahadik KR. New drug delivery systems for elderly. Indian Drugs 2000; 37(7): 312-318.
13) Noviasky; John A; Porsteinsson; Anton P; Lee; Yeong H. Second Generation Anticonvulsant Medications: Their Use in Children. The J of School Nursing 2001; 17(2): 103-111.
14) Stefani A; Spadoni F; Bernardi G. Voltage-activated calcium channels: targets of antiepileptic drug therapy? Epilepsia 1997; 38(9): 959-965.
15) Kavitha K; Nalini CN; Kasturi GD; Merlin JP; Varalakshmi V; Maragatham C. Effect of betadex on the solubility and dissolution behaviour of rofecoxib. The Antiseptic 2004; 101(10): 463-465.
16) Lalla JK, Mamania HM. Fast dissolving rofecoxib tablets. Ind J Pharm Sci 2004; 66(3): 350-352.
17) Nayak SM; Gopikumar P. Design and optimization of fast dissolving tablets for promethazine theoclate. Indian Drugs 2004; 41(9): 554-556.
18) Shimizu T; SugayaM; NakanoY; IzutsuD; Mizukami Y; Okochi K et al. Formulation study for lansoprazole fast disintegrating tablet.III. Design of rapidly disintegrating tablets. Chem Pharm Bull 2003; 51(10): 1121-1127.
19) Pandey S; Agrawal S; Shenoy V. Optimizing fast dissolving dosage form of diclofenac sodium by rapidly disintegrating agents. Ind J Pharm Sci 2003; 65(2): 197-201.
20) Chowdary KPR; Hymavathi R. Formulation and dissolution rate studies on dispersible tablets of ibuprofen. Ind J Pharm Sci 2000; 62(3): 213-216.
21) Chowdary KPR; Rama Rao N. Formulation and evaluation of dispersible tablets with pregelatinized starch.Indian Drugs 1998; 35(6): 368-371.