FORMULATION, DEVELOPMENT AND OPTIMIZATION OF FAST DISPERSIBLE ORAL FILMS OF DOMPERIDONE MALEATE

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ABOUT AUTHORS:
Krupa Mehta, Nitu Changoiwala, Sanjay C. Modi, Dr. Mukesh C. Gohel, Dr. Rajesh K. Parikh
L. M. College of Pharmacy, Navrangpura,
Ahmedabad, Gujarat-380009, India

ABSTRACT:
Objective:
To Formulate, Develop and Optimize fast dispersible oral films of Domperidone maleate.
Materials and Methods:
Fast dispersible films of Domperidone maleate were prepared using solvent casting method. Films were formulated using Hydroxy Propyl Methyl Cellulose (HPMC-E5) as a film forming agent, PEG-400 as a plasticizer. A 32 full factorial design was applied systematically to optimize the drug release and folding endurance. The concentration of HPMC-E5 (X1) and concentration of PEG-400 (X2) were selected as independent variables.
  The Percentage Drug Release in 5 minutes (Y1) and Folding endurance (Y2) were selected as dependent variables. The prepared films were evaluated for Thickness, Folding endurance, Tensile Strength, Disintegration time, In vitro drug release and Drug content uniformity.  DSC studies were conducted for drug-excipient interactions.
Results: Films prepared were found to be of good quality fulfilling all the requirements. Regression analysis and numerical optimization were performed to identify the best formulation. Formulations F10 prepared with 2.7% HPMC-E5 and 20% PEG-400 was found to be the best formulation with 96% Drug release in 5 minutes and folding endurance 24.
Discussion: X1 and X2 significantly affected the Percentage Drug Release in 5 minutes (Y1) and Folding endurance (Y2). Percentage Drug Release decreased as the concentration of HPMC-E5 and PEG-400 increased. Folding endurance increased as the concentration of HPMC-E5 and PEG-400 increased.
Conclusions: Fast dispersible films of Domperidone maleate were successfully formulated by Solvent casting technique with immediate onset of action & improved patient compliance.

REFERENCE ID: PHARMATUTOR-ART-2045

PharmaTutor (ISSN: 2347 - 7881)

Volume 1, Issue 2

Received On: 27/10/2013; Accepted On: 05/11/2013; Published On: 20/12/2013

How to cite this article: Mehta K, Changoiwala N, Modi S, Gohel M, Parikh R, Formulation, Development and Optimization of Fast Dispersible Oral Films of Domperidone Maleate, PharmaTutor, 2013, 1(2), 75-87

INTRODUCTION:
Fast dispersing film, a new drug delivery system for oral delivery of drugs consists of a very thin oral strip, which releases the active ingredient immediately after the uptake into the oral cavity. The delivery system is simply placed on the patient’s tongue or any oral mucosal tissue, instantly wet by saliva the film rapidly hydrates and adheres onto the site of application. It then rapidly disintegrates and dissolves to release the medication for oromucosal absorption or with formula modifications, will maintain the quick-dissolving aspects and allow for gastrointestinal absorption to be achieved when swallowed1. Fast Dispersing Films are a convenient way to deliver active pharmaceutical ingredients to the patient because they are easier to swallow. No water is needed for the filmstrips to dissolve, so it can be taken any time anywhere2. Such new drug delivery systems thus have been designed keeping in view the problems faced by pediatrics and geriatrics having difficulty in swallowing or chewing solid dosage forms3.

It offers several advantages with respect to its administration without water, accurate dosing, easy manufacturing, ease of handling and administration and a pleasant taste.4-5 “Quick Dissolving Film” for oral mucosal delivery overcomes the shortfalls of conventional fast-dissolving intraoral tablets. Films can be produced with manufacturing process that is competitive with the manufacturing costs of conventional tablets. Thus it allows children, elderly, and the general population to take their medications discretely wherever and whenever needed, satisfying an unmet need. Since the absorption is taking place directly from the mouth, so, bioavailability of the drug increases6. This type of drug delivery is becoming popular day by day due to its numerous advantages.

Fast dispersing films should be stiff, flat, and should not curl on the edges. For consumer acceptance, the water soluble film strip should be tough enough so that there won’t be any damage while handling or during transportation7. The robustness of the strip depends on the type and concentration of polymer8. The strip must also dissolve readily in order to deliver the API rapidly when placed on the tongue, so that a gummy texture is avoided. Mechanical property of quick dissolve film is as important as its solubility rate. The most important component in the film matrix, which can achieve these characteristics, is to choose the correct polymer system. Careful balancing of the mechanical properties and solubility rate for the film strip is required which depends on the polymer matrix employed to design fast dispersing films.

HPMC forms transparent, tough and flexible films from aqueous solutions9,10. There is inverse relationship between mechanical properties and solubility rate for HPMC11,12, therefore these two properties must be carefully balanced when designing, so that the stiff film strip can be efficiently cut to size, and filled into unit-dose packaging while still having rapid dissolution. By using optimum amount of water soluble film formers and plasticizer, it is possible to prepare fast dispersing films of Domperidone with acceptable mechanical strength and rapid disintegration.

Domperidone maleate is indicated for treatment of nausea and vomiting13. It is described as a first line treatment for nausea in Parkinson’s disease. It is antiemetic of choice in acute migraine. It is also used in non ulcer dyspepsia. It is used in patients with dysmotility. Domperidone maleate is white solid with molecular weight of 542.0 g/mol14. It is very slightly soluble in water14.

The objective of the present study was to develop fast dispersible taste masked oral films of Domperidone maleate. Films were formulated using HPMC E5 as a film forming agent, PEG-400 as a plasticizer, Polysorbate 80 as surfactant, menthol as flavoring agent and Neotame as sweetening agent.

MATERIALS AND METHODS:

Materials:
Domperidone maleate was obtained from Cadila Pharmaceuticals, India. HPMC E5 was obtained from Signet Chemicals, Mumbai. PEG-400 was obtained from Burgoyne Urbidges & co. Menthol was obtained from Raj Shah Pharmaceuticals. Neotame was obtained from Kawarlal & Co., Chennai and Polysorbate 80 from SD’S Chem Lab, Mumbai. All other solvents and reagents used were of analytical grade.

Method:
Spectroscopic Analysis of Domperidone maleate:
In the present investigation, Domperidone maleate has been estimated by UV/Visible Spectrophotometry. The drug release study was carried out using simulated saliva (pH 6.8) as the dissolution medium.

Preparation of Standard Curve:
· For preparation of stock solution, the drug Domperidone maleate (100 mg) was dissolved in 100 ml of simulated saliva to obtain a solution ‘A’ (1000 µg/ml). The 10 ml of solution ‘A’ was diluted to 100 ml with simulated saliva to get solution ‘B’ (100 µg/ml).
·The 1 ml of the stock solution was diluted to 20 ml using simulated saliva (5 µg/ml).
· Aliquots of 2,3,4,5,6,8,10,15,20 ml of the stock solution were serially diluted with simulated saliva to 20 ml to get 10,15,20,25,30,40,50,75,100 µg/ml concentrations respectively.
· The absorbance of each solution was measured at 287 nm against simulated saliva as a blank. λmax of Domperidone maleate in simulated saliva is found to be at 287nm.
· The assay was performed in triplicate and average absorbance was considered.

Formulation of Domperidone maleate Fast Dispersible films:
Preliminary studies were carried out to optimize a suitable polymer and plasticizer system and to obtain films of desirable mechanical property and dissolution characteristics.

In order to investigate the effect of formulation variables on the response variables, and to predict an optimized formulation, a 32 factorial design was adopted. List of Independent variables and Dependent variables are mentioned in Table1.

Table 1: Selection of Independent variables and Dependent variables

32 full factorial design

Independent variables

Dependent variables

X1

X2

Y1

Y2

Concentration of HPMC E5       (mg)

Concentration of PEG-400     (%of Polymer)

%Drug release in 5minutes

Folding   endurance

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