RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA, BANGALORE.

ANNEXURE – II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / Name of the Candidate
and Address / Mr. Ashok N.Pai
A/304, Krishna Regency, Near Dalmiya College, Behind Sundar Nagar, Malad West , Mumbai-400064
2. /
Name of the Institution
/ SHREE DEVI COLLEGE OF PHARMACY,
Airport Road,Kenjar villege,Malavoor Panchayat,
Mangalore.
Pin -574142
3. / Course of Study and Subject / M. Pharm
(Pharmaceutics)
4. /
Date of Admission
/
July 2011
5. TITLE OF THE PROJECT:-
FORMULATION DEVELOPMENT OF MOUTH DISSOLVING TABLETS
OF AN ANTIEMETIC DRUG
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6.1
6.2
6.3
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7.1
7.2
7.3

7.4
7.5 / BRIEF RESUME OF THE INTENDED WORK:
NEED FOR THE STUDY:
Mouth dissolving tablets (MDT) are a new generation of formulations which combine the advantages of both liquid oral and conventional tablet formulations. They provide the convenience of a tablet formulation and also allow the ease of swallowing provided by a liquid formulation.1
The cause of nausea and vomiting could be from a lot of conditions such as motion sickness, gastrointestinal disorders, drug toxicity, cancer chemotherapeutic agents, peptic ulcer, hepatitis, renal failure and pregnancy. Discomfort from drug induced emesis can deter a patient from taking further chemotherapeutic agent especially with the potentially curative anti neoplastic treatment. Vomitingthat is not controlled can lead to dehydration, nutrient loss and profound metabolic imbalances.2These tablets releases the medicament in the mouth for absorption through local oromucosal tissue and through pre-gastric (oral cavity, pharynx and oeso-phagus), gastric (stomach) and post-gastric (small and large intestine) segments of the gastrointestinal tract.
Orally disintegrating dosage forms are particularly suitable for patients, who have difficulty to swallow traditional tablets with a glass of water. Other factors are as follows,
  • Pediatric and geriatric patients who have difficulty in swallowing or chewing solid dosage forms.
  • Patients who are unwilling to take solid preparation due to fear of choking.
  • Very elderly patients who may not be able to swallow a daily dose of antidepressant.
  • An eight-year old child with allergies who desires a more convenient dosage form than antihistamine syrup.
  • A middle-aged woman undergoing radiation therapy for breast cancer may be too nauseous to swallow her H2- blocker.
  • A schizophrenic patient in an institutional setting who may try to hide a conventional tablet under his or her tongue to avoid their daily dose of an atypical antipsychotic drug.
  • A patient withpersistent nausea, who may be in journey, or has little or no access to water.3
  • MDTs offer several advantages over other dosage forms like effervescent tablets, dry syrups and chewing gums/tablets.
  • More rapid drug absorption from the pre-gastric area i.e. mouth, pharynx and oesophagus which may produce rapid onset of action.
  • Pregastric absorption can result in improved bioavailability, reduced dose and improved clinical performance by reducing side effects.
Immediate release (Fast dissolving) drug delivery systems can be achieved by various conventional methods like direct compression, wet granulation, molding, spray drying, freeze drying and sublimation. Immediate release (Fast dissolving) tablets disintegrate and/or dissolve rapidly in the saliva without the need for water. Some tablets are designed to dissolve in saliva remarkably fast, within a few seconds, and are true fast-dissolving tablets. The major advantage of the fast dissolving tablet formulation is that it combines the advantages 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 allowing the ease of swallowing provided by a liquid formulation.4
REVIEW OF LITERATURE:
  • Nausea and vomiting continues to be an important problem for cancer patients receiving chemotherapy. Chemotherapy-induced nausea and vomiting (CINV) are classified as acute, occurring within the first 24 h, or delayed, occurring after the first 24 h. A number of antiemetic agents are available for the management of nausea and vomiting, including 5-HT3-receptor-antagonists, corticosteroids, NK-1-receptor-antagonists,dopamine-receptor antagonists, benzodiazepines, neuroleptics and cannabinoids.With modern antiemetic therapy, vomiting can be prevented in 70–80% of patients, whereas the control of nausea remains suboptimal.5
  • A five-drug combination, including metoclopramide, thiethylperazine, diphenhydramine, dexamethasone, and diazepam, was given to 32 patients during three consecutive treatments with chemotherapy. Eighteen patients (group A) were treated with a cisplatin-containing regimen, and 14 patients (group B) were treated with a cyclophosphamide- and doxorubicin-containing chemotherapy. In group A, complete responses were lower on the first day than on the second and third days (P< 0.015 andP< 0.041, respectively), during the first and second courses. The five-antiemetic drug regimen seems safe and effective. These results show that clinical trials that evaluateantiemetic efficacy in cisplatin-containing chemotherapy regimens should evaluate at least two consecutive courses.6
  • Nausea and vomitingare difficult symptoms to manage in patients with advanced cancer. Several classes ofantiemeticare available, including phenothiazines, butyrophenones, substituted benzamides and selective serotonin antagonists, as well as corticosteroids. Most patients will respond to either single agents or combinations that frequently include corticosteroids. A minority of patients will havenauseathat fails to respond. The atypical antipsychotic,olanzapine, relievesnauseain some patients failing to respond to the usual.7
  • Thirty-seven patients with advanced malignancies, who receivedcis-platinum-based combination chemotherapy, were evaluated for theantiemetic efficacy of high-dose metoclopramide. Most of the patients suffered from ovarian carcinoma. The dose of metoclopramide was 7.5 or 10 mg/kg per course. A total of 69 courses were given to 37
patients and in 22% of the courses, nausea and vomiting were eliminated altogether. In an additional 48% of the courses, a partial protection from chemotherapy-induced emesis was evident. No serious side effects were observed. The administration of high-dose metoclopramide is recommended for prevention ofcis-platinum chemotherapy-induced emesis.8
  • In a prospective, randomized, double-blind trial the combination betamethasone-dixyrazine was compared with high-dose metoclopramide asantiemetic treatment during combination chemotherapy (melphalan-doxorubicin and cisplatin) of ovarian carcinoma. Of 40 evaluable patients, 15 (38%) had previous experience with chemotherapy. Efficacy and side effects were recorded on patient and nurse questionnaires using the visual analog scale. Nausea and vomiting were prevented in 55% of the patients treated with melphalan-doxorubicin (Day 1) and in 36% of the patients treated with cisplatin (Day 2). Betamethasone-dixyrazine was superior to high-dose metoclopramide and prevented nausea in 76% compared to 32% during melphalan-doxorubicin therapy. Akathisia was noted in 21% and acute dystonic reactions in 2.6% during metoclopramide treatment but not in any case during betamethasone-dixyrazine therapy.9
  • The objective was to assess theantiemeticactivity of granisetron, dexamethasone and droperidol in the otologic surgeries. Sixty patients in ASA (American Society of Anesthesiologists) I and II risk groups who underwent surgery forchronic otitis mediawere assessed in a double blind and randomized trial. The patients were divided into three equal groups. Single intravenous dose ofgranisetron(3 mg),granisetron(3 mg) plusdexamethasone(8 mg) anddroperidol(1.25 mg) were prophylactically administered to the patients in group 1, group 2 and group 3, respectively, and theirantiemetic actions were compared. Theantiemeticeffects of thedrugs were not significantly different between the groups (P>0.05). Theantiemetic effects also did not differ significantly in the early and late postoperative periods (P>0.05). In conclusion, the results of prophylactic use or side effects ofgranisetron,plusdexamethasoneordroperidolare similar inmiddle earsurgery. Therefore, cost effectiveness of theantiemetic prophylaxis should be reconsidered in otologic surgery in the light of the results of this study.10
OBJECTIVES OF THE STUDY:-
  1. To carry out pre-formulation studies.
  2. To design and develop fast dissolving tablets by direct compression method.
  3. To carry out the morphological characteristics of the drug
  4. To carry out in-vitro release studies using U.S.P. II dissolution test apparatus.
  5. To evaluate in-vitro disintegration time of formulation.
  6. To carry out stability studies
  7. To carry out the evaluation studies. The parameters are Shape, size, hardness, thickness, friability, drug content uniformity, weight variation test, wetting time, in-vitro dispersion time, in-vitro disintegration time.
MATERIALS AND METHODS:
SOURCE OF DATA:-
1)Review of literature from:
  1. Journals – such as
  2. Indian Journal of Pharmaceutical Sciences
  3. European Journal of Pharmaceutical Sciences
  4. Asian Journal of Pharmaceutics
  5. International Journal of Pharmaceutics
  6. Drug development and Industrial pharmacy
  7. Indian Drugs
  8. Journal of Pharmaceutical Research
  9. World Psychiatry
  10. World Wide Web
  11. J-Gate@Helinet
MATERIALS AND EQUIPMENT:
MATERIALS:
  • Drug : Antiemetic
  • Superdisintigrants : Cromscarmellose sodium, crosspovidone, sodium starch
Glycolate, calcium silicate will be used.
  • Excipients :The various excipient like talc, starch, Magnesium
stearate will be used.
EQUIPMENT:
  • Tablet compression machine
  • Granulator
  • Sieve no-40
  • UV Visible Spectrophotometer
  • Tablet Dissolution Test Apparatus
  • Tablet Disintegrating Test Apparatus
  • Analytical balance
  • FTIR
MethodS:-
  1. To carry out preformulation studies like drug-excipient interaction.
  2. Preparation of immediate release tablet by direct compression technique.
  3. Characterization of fast dissolving tablets by following parameters:-
a)Preformulation parameters
  • Micromeritic properties: Angle of repose, bulk density, percentage compressibility.
b)Post-compression parameters
  • Shape, size, hardness, thickness, friability, drug content uniformity, weight variation test, wetting time, in-vitro dispersion time, in-vitro disintegration time.
  1. Statistical analysis of data will be obtained from the results.
DOSE THE STUDY REQUIRES ANY INVESTIGATION OR INVESTIGATIONS 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 / REFERENCES:-
  1. Shukla D, Chakraborty S, Singh S, Mishra B.Mouth Dissolving Tablets II: An Overview of Evaluation Techniques. Sci Pharma S2009;77:327–41.
  2. Nosiri CI,Alewu B,Gambo A.Preliminary Study of the Antiemetic Effect of Garcinia Kola Seed Extract in Young Chicks.The Internet Journal of Alternative Medicine 2010;8(2).
  3. Khinchi M, Gupta MK, Agarwal D, Sharma N, Wadhwa S.Orally disintegrating tablets a future prospect. Int j pharm sci biotech
  4. Bogner RH, Wilkosz MF. Fast-Dissolving Tablets- New Dosage Convenience for Patients. U. S. pharm 2002;27:34-43.
  5. Jordan K, Schmoll HJ, Aapro MS. Comparative activity of antiemetic drugs. Critical Reviews in Oncology/Hematology 2007;61:162–75.
  6. Aydiner A, Onat H, Ozturk N, Aykan F, Inanc S, Topuz E, Dincol K.The efficacy of a five-drugantiemetic combination during chemotherapy regimens containing cisplatin or cyclophosphamide-doxorubicin.Journal of Pain and Symptom Management 1993;8(3):126-31.
  7. Srivastava M, Norman BD, Davis MP, Marie L, Lagman R.Olanzapine as an antiemetic in Refractory nausea and vomiting in advanced cancer.Journal of Pain and Symptom Management2003;25(6):578-82.
  8. Gez E, Catane R, Pfau L, Biran S.High-dose metoclopramide as an antiemetic in patients receivingcis-platinum-based combination chemotherapy.Gynecologic Oncology 1985;21(1):18-22.
  9. Sorbe B, Christer H. Antiemetictreatment of chemotherapy-induced nausea in ovarian carcinoma patients.Gynecologic Oncology 1989;34(2):141-44.
  10. Goksu S, Kocoglu H, Bayazit YA, Yuksek S, Karci Y, Muzaffer Kanlikama M, Unsal Oner. Antiemetic effects of granisetron, droperidol and dexamethasone in otologic surgery.Auris Nasus Larynx 2002;29(3):253-56.

9 / Signature of the candidate:
10 / REMARKS OF THE GUIDE:
FORMULATION DEVELOPMENT OF MOUTH DISSOLVING TABLETS OF AN ANTIEMETIC DRUGto be carried out by Mr. Ashok N.Pai. of M. Pharm has been discussed and worked out under my directions and supervision as an official guide. The project work envisaged is of great importance in the field of Pharmaceutical Formulation. The work can be carried out in Pharmaceutics laboratory of Shree Devi College of Pharmacy for which facilities are available. Hence the project is viable and is recommended for clearance and approval.
11 / Name and Designation:
11.1 / Institutional Guide: / Mr. NARAYANRAJU PADALA
Asst.Professor
Shree Devi Collage of Pharmacy.Mangalore.
11.2 / Signature:
11.3 / Head of the Department: / Dr. R P Ezhil Muthu.
Professor
Shree Devi College of Pharmacy.Mangalore.
11.4 / Signature
12.1 / Remarks of the Principal:
The Programme and the Research work that is undertaken by Mr.Ashok N.Pai. have potential implication in the field of Pharmaceutics. The work can be carried in the Research Laboratories of Pharmaceutics Department at Shree Devi college of Pharmacy. Hence the Project is recommended and requested for clearance and approval.
12.2 / Signature / Dr. Jagadish V. Kamath
Principal,
Shree Devi college of pharmacy,
Mangalore.

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