FORMULATION AND EVALUATION OF ORAL DISPERSIBLE FILM OF AN ANTIEMETIC DRUG.
M. Pharm. Dissertation Protocol Submitted to
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore– 560041
By
MS. KAVITA.S.YADAWAD B. Pharm.
Under the Guidance of
Dr. M.S.SRINATH M.Pharm, PhD.
Department of Pharmaceutics
S.E.T’s COLLEGE OF PHARMACY
S. R. Nagar, Dharwad–580002
2011-2013
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / NAME OF THE CANDIDATE AND ADDRESS / MS.KAVITA.S.YADAWADDEPT. OF PHARMACEUTICS
SET’s COLLEGE OF PHARMACY,
S.R.NAGAR,
DHARWAD-580002
2. / NAME OF THE INSTITUTION / SET’s COLLEGE OF PHARMACY,
S. R. NAGAR,
DHARWAD-580002
3. / COURSE OF STUDY AND SUBJECT / MASTER OF PHARMACY IN PHARMACEUTICS
4. / DATE OF ADMISSION TO COURSE / JUNE-2011
5. / TITLE OF THE TOPIC
FORMULATION AND EVALUATION OF ORAL DISPERSIBLE FILM OF AN ANTIEMETIC DRUG.
6.
7. / BRIEF RESUME OF THE INTENDED WORK
6.1 NEED FOR THE STUDY
A fast dissolving system is defined as a dosage form for oral administration, which when placed in mouth, rapidly dispersed or dissolved and can be swallowed in the form of liquid. Recently fast dissolving formulation is popular as Novel Drug Delivery System because they are easy to administer and lead to better patient compliance. Pediatric and geriatric patients have difficulty in swallowing the conventional dosage forms. Fast dissolving and fast dispersing drug delivery system may offer a solution to these problems1,2,3.
Fast dissolving films have attained great importance in the pharmaceutical industry due to their unique properties and advantages4, 5. This delivery system consists of a very thin oral strip, which is placed on the patient’s tongue or any oral mucosal tissue.They undergo disintegration in the salivary fluids of the oral cavity within a minute where they may release the active pharmaceutical ingredient6,7. Availability of larger surface area of the film leads to rapid disintegration in the oral cavity8, 9.
The oral or buccal mucosa being highly vascularized, drugs can be absorbed directly and can enter the systemic circulation without undergoing first‐pass hepatic metabolism. This is one of the added advantage of orodispersible formulation as little quantity of the drug may get absorbed in the buccal cavity, can be exploited in preparing products with improved oral bioavailability of molecules that undergo firstpass effect8,9.
Water is not required for administration of film, that leads to better acceptability amongst the dysphagic patients. The difficulty encountered in swallowing tablets or capsules is circumvented. The dosage form can be consumed at anyplace and anytime as per convenience of the individual8,15.
The disadvantage of most Oral dispersible tablet is that they are fragile and brittle, which required special packaging for protection during storage and transportation. Since the films are flexible they are not fragile. Hence, there is ease of transportation, consumer handling and storage8,9.
The Oral dispersible films are essentially prepared using water soluble and fast disintegrating polymers which also possess good film forming properties like hydroxypropyl methylcellulose (HPMC), polyvinyl pyrolidone(PVP), polyethylene oxide (PEO) and hydroxypropylcellulose(HPC)4,10,11.
Antiemetics are used to prevent or suppress vomiting. These are well absorbed in oral cavity. The antiemetics in the form of tablet, capsule, are administered, to patients suffering from emesis may expel out the drug leading to reduced or no therapeutic action. Hence Oral dispersible film came because of its easy administration, handling and storage. Moreover Fast dissolving film would serve as an ideal dosage form for the pediatrics and geriatric patients. Due to its ease of usage and high acceptability, Oral dispersible film was formulated in the present investigation.
The objective of the present investigation is to develop formulations of Oral dispersible film of an antiemetic drug using appropriate grade of film forming polymers.
6.2 REVIEW OF LITERATURE:
Kunte S, et al., demonstrated significant taste masking of verapamil and rapid disintegration of fast dissolving oral strips. They formulated all the oral strips by using different concentration of HPMC E6 and maltodextrin found to disintegrate in less than 30 seconds. They developed in vitro and in vivo evaluation of the films and confirmed their potential as an innovative dosage form to improve delivery of verapamil. Finally they concluded that bitter drugs such as verapamil can be successfully formulated and can be useful for geriatric, bedridden and noncooperative patients due to its ease of administration12.
Hiroyoshi S, et al., prepared for the first time a fast dissolving oral thin film containing dexamethasone and base materials, including microcrystalline cellulose, polyethylene glycol, hydroxypropylmethyl cellulose, polysorbate 80 and low-substituted hydroxypropyl cellulose. The preparation revealed excellent uniformity and stability of dexamethasone and rapidly disintegrated in water. They observed no significant differences in pharmacokinetic parameters obtained from rats with oral administration of dexamethasone suspension and those with topical application of the film to the oral cavity. Hence fast-disintegrating oral film containing dexamethasone is considered to be potentially useful for cancer patients with disturbansce in eating and swallowing who receive radiotherapy and/or high- to moderate emetogenic anticancer drugs13.
Cilurzo F, et al., prepared fast dissolving films of meltodextrins, Maltodextrins having dextrose equivalent to 12 plasticized with 16–20% w/w glycerin are suitable to produce fast-dissolving films by different manufacturing processes, such as casting and solvent evaporation or hot-melt extrusion. Homogeneous films are achievable by loading a large amount of water insoluble powders, namely more than 15% w/w. When piroxicam was selected as a model drug, the film can contain more than 25 mg of active ingredient for a surface of 6 cm2. The loading of a drug as a powder in the film determined a decrease of the ductility, but the formulations maintained satisfactory flexibility and resistance to elongation for the production and packaging procedures.Compared to the hot-melt extrusion method, the casting method appeared more reliable for the production of fast-dissolving films since the dosage forms exhibited the highest patients’ compliance and best performances in terms of in vitro and in vivo disintegration time. Furthermore, the films remarkably improve the dissolution of poorly soluble drugs, such as PRX which completely dissolved within 10 min independently of the drug loading14.
Reiner V, et al., Additionally compared to a Rapidfilm, Oral dispersible tablets are rather big and bulky. So, the thin film may alleviate the fear of swallowing and the risk of choking commonly associated with a conventional tablet. Furthermore, the fast-dissolving action, primarily due to the wide surface area of the film, which wets quickly when exposed to the moist oral environment, can make Rapidfilm dissolving in small amounts of liquid: this can be beneficial for people suffering from reduced salivary secretion including chemotherapy- and/or radiotherapy-induced mucositis or sicca syndroma (Sjögren’s syndrome). In conclusion the Rapidfilm delivery system, by alleviating the administration by the end-user and by allowing patients to take their medication anytime and anyplace under all circumstances, can result in higher convenience for several applications15.
Prabhu P, et al., Prepared fast-dissolving films of levocetirizine dihydrochloride can be considered suitable for clinical use in the treatment of allergic rhinitis and other conditions like allergies, where quick onset of action for a dosage form is desirable along with convenience of administration. The method of preparation is found to be simple and thus product cost is effective. In vivo study proved that fast-dissolving films of levocetirizine di hydrochloride produced a faster onset of action as compared to conventional tablets16.
6.3 OBJECTIVE OF STUDY:
The objectives of the proposed study are:-
§ To prepare standard calibration curve of an antiemetic drug.
§ To carry out compatibility studies between drug & polymer.
§ To develop Oral dispersible films.
§ To evaluate formulations for various quality control parameters.
Materials and methods :
materials :
Drug: An Antiemtic drug.
Polymer: Suitable hydrophilic polymers like HPMC, PVP, PEO, PVA etc.
7.1 METHOD :
A. PREPRATION OF FILMS BY THE METHODS LIKE:
1. Solvent casting method.
2. Semi solid casting method.
B. EVALUATION STUDIES :
· Thickness.
· Weight variation.
· Drug content.
· Tensile strength.
· Surface pH.
· Disintegration test.
· In vitro dissolution test.
· Films are subjected to Fourier Transform Infrared Radiation (FTIR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC) and X-ray diffraction (XRD).
7.2 SOURCE OF DATA :
· Text books
· www.sciencedirect.com
· www.informahealth care.com
· www.ijps online.com
7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INVENTION TO BE
CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS? IF SO
PLEASE MENTION BRIEFLY.
No.
7.4 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR
INSTITUTION IN CASE OF 7.3?
Not applicable.
1
8. / REFERENCES:1. Seager H. Drug-deliver products and the zydis fast-dissolving dosage form. J Pharm Pharmacol 1998;50:375-82.
2. Parmar RB, Baria AH, Tank HM, Faldu SD. Formulation and Evaluation of Domperidone Fast-Dissolving Tablets. Int J Pharm Tech Res 2009 July-Sept; 1(3):483-7.
3. Ghorwade V, Patil A, Patil S, Ikkurthi K, Inuganti KS, Porandla V. Formulation and evaluation of Montelukast sodium fast dissolving films by using Gelatin as a film base. RJPBCS 2011 Jul-Sep;2(3):880-8.
4. Mishra R, Amin A. Formulation and characterization of rapidly dissolving films of cetrizine hydrochloride using pullulan as film forming agent. Ind J Pharm Edu Res 2011 jan-mar;45(1).
5. Borsadia S,O’Halloran D, Osborne JL. Quick Dissolving Films –A Novel Approach to Drug Delivery Tech 2003;3(3):63-6.
6. Klancke J. Dissolution Testing of Orally Disintegrating Tablets. Dissolution Tech 2003;10(2):6-8.
7. Joshi AA, Duriez X. Added functionally excipients: An answer to challenging formulations . Pharma techno excipients and solid dosage forms 2004.
8. Gavaskar B, Vijayakumar S, Sharan G,MadhusudhanRao Y. Overview on fast-dissolving films. Int J Pharma and Pharm Sci 2010;2(3):29-33.
9. Saini S, Nanda A, Hooda M, Komal. Fast dissolving films(FDF):Innovative drug delivery system. Phamacologyonline 2011;2:919-28.
10. Corniello CM. Quick- Dissolving Strips: From Concept to Commercialization. Drug Deli Tech 2006;6(2):68-71.
11. Vondrak B, Barnhart S. Dissolvable films for flexible product format in drug dlivery. Pharm Tech 2008;S20-8.
12. Kunte S, Tandale P. Fast dissolving strips;A novel approach for the delivery of
Verapamil. JPBS 2010 Oct-Dec;2(4),327-8.
13 Shimoda H, Taniguchi K, Nishimura M, Matsuura K, Tsukioka T, Yamashita H
et al. Preparation of a fast dissolving oral thin film containing dexamethasone:A
possible application to antiemesis during cancer chemotherapy. EJPB 2009;73:361-5.
14. Cilurzo F, Irma E, Cupone, Minghetti P, Selmin F, Montanari L. Fast dissolving
Films made of maltodextrins. EJPB 2008;70:895–900.
15. Reiner V, Giarratana N, Ceppi Monti N, Breitenbach A, Klaffenbach P.
Rapidfilm®: An innovative pharmaceutical form designed to improve patient
compliance. Ijpharm 2010;393:55-60.
16. Prabhu P, Malli R , Koland M , Vijaynarayan K, D’souz U, Harish NM et al.
Formulation and evaluation of fast dissolving films of levocitirizine di
hydrochloride. Int J pharma inve 2011 Apr ;1(2).
9. / SIGNATURE OF CANDIDATE
10. / REMARK OF THE GUIDE
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.
11. / 11.1 NAME AND DESIGNATION
OF THE GUIDE
11.2 SIGNATURE / Dr. M.S.SRINATH M.Pharm, PhD
DIRECTOR
DEPT.OF PHARMACEUTICS,
S E T’s COLLEGE OF PHARMACY,
S. R. NAGAR, DHARWAD-580002.
11.3 NAME AND DESIGNATION
OF CO-GUIDE
11.4 SIGNATURE /
------
11.5 HEAD OF THE
DEPARTMENT
11.6 SIGNATURE / Prof. S. P. THAKKER M. Pharm.
PROFESSOR AND HEAD,
DEPT.OF PHARMACEUTICS,
S E T’s COLLEGE OF PHARMACY,
S. R. NAGAR, DHARWAD-580002.
12. / 12.1 REMARK OF THE
PRINCIPAL
/ The above mentioned information is correct and I recommend the same for approval.
12.2 SIGNATURE /
Dr. V. H. KULKARNI M.Pharm, Ph.D.,
PROFESSOR AND PRINCIPAL,
S E T’s COLLEGE OF PHARMACY
S. R. NAGAR,
DHARWAD-580002.
9