Formulation and Evaluation of Quick Dissolving Films of Promethazine Hydrochloride

 

Nikhlesh Birla, Kavita Mandloi, Rampal Mandloi*, Dr. Sujit Pillai

GRY Institute of Pharmacy, Vidhya Vihar Borawan- 451228, Khargone (M.P)

 

ABSTRACT:

Fast dissolving dosage forms have acquired great importance in pharmaceutical industry because of their unique properties like dissolve upon contact with a wet surface, such as the tongue, within a few seconds, meaning the consumer can take the product without need for additional liquid. This convenience provides both a marketing advantage and patient compliance. The present study aimed at preparing fast dissolving oral films of Promethazine Hydrochloride oral fast dissolving films that offers a suitable approach for the treatment and management of nausea and vomiting. In the present investigation different types of polymer like HPMC, HPC, polyvinyl pyrolidone, aspartame, poly vinyl alcohol to prepare quick films. The prepared films were evaluated for film thickness, folding endurance, surface pH, morphological properties, % drug content and content uniformity, tensile strength, percent elongation, in vitro disintegration time and in vitro dissolution studies.

The physical appearance was found to be good and shows that films were transparent physical appearance was found to be good and shows that films were transparent with smooth surface without any scratches. The folding endurance was showed that films have good flexibility. In-vitro drug release for Promethazine of all the formulations showed 60-90% within four minutes.

 

 

 

INTRODUCTION:

Oral route is the most preferred route of administration of drugs because of accurate dosage, self medication, low cost and ease of administration leading to high level of patient compliance. The buccal cavity is an attractive route of administration for Systemic drug delivery. Oral mucosa has a rich vascularization and offers higher permeability to many drugs. It has been well known that after buccal and sublingual administration drug solutes are rapidly absorbed in to the reticulated vein and are then drained into the systemic circulation^1,3,4.

 

The concept of Fast Dissolving Drug Delivery System emerged from the desire to provide patient with a conventional mean of taking their medication. Difficulty in swallowing (Dysphagia) is a common problem of all age groups, especially elderly and paediatrics, because of physiological changes associated with these groups of patients. Recently  Various bio-adhesive and mucosal dosage forms have been formulated which includes adhesive tablets, gels, ointments, patches and more recently the mouth disintegrating films have been emerges out as a new drug delivery system that provides a very convenient means of taking medications and supplements. ^2,6

 

MATERIALS AND METHOD:

Materials:

Promethazine Hydrochloride, Asparmate, HPMC, HPC, Poly vinyl pyrolidone, Poly vinyl alcohol, Propylene glycol, ethanol.^5,10

Method:

In the present study, fast dissolving films of Promethazine Hydrochloride were prepared by solvent casting technique. Flat, square-shaped, glass moulds having a surface area of 25 cm² were fabricated for casting the films. ^[9]

 

Preparation of casting solutions:

The casting solutions were prepared by dissolving weighed quantities of polymers (Table 1 ) in 10 ml of ethanol taken in a beaker. The drug and aspartame were dissolved in 5 ml of ethanol and added to the above polymer solution along with propylene glycol, as plasticizer, thoroughly mixed to form a homogeneous mixture. The volume was made up to 20 ml with ethanol. The beaker was covered with aluminium foil and the solution was allowed to stand overnight to remove air bubbles.⁸

 

Preparation of fast dissolving films:

The casting solution (20 ml) was poured into glass moulds and kept a side covered with funnel to allow for controlled evaporation. The films were removed by peeling and cut into square dimension of 2 × 2 cm (4 cm2), so, that each film contained about 10 mg of drug. These films were kept in desiccator for 2 days for further drying and wrapped in aluminium foil, and packed in self-sealing covers.

 

Table 1- Composition of fast dissolving films ¹⁴

 

Characterization parameters:^{3, 4,6}

Film Thickness:

The thickness of 3 films of each formulation was performed by screw gauge at different position of the film and the average thickness was calculated.

 

Uniformity of weight:

The film (4 cm²) was cut at five different places in the cast film. The weight of each filmstrip was taken and the weight variation was calculated.

 

Uniformity of drug content:

This parameter was determined by dissolving one film of dimension 2x2 cm containing 10 mg of Promethazine by homogenization in 100 ml of simulated salivary fluid, the absorbance was measured at 250 nm using a UV spectrophotometer and the drug content was calculated.^11,13

 

Folding endurance:

The folding endurance is expressed as the number of folds (number of times the film is folded at the same place) required to break the specimen or to develop visible cracks. This also gives an indication of brittleness of the film. A strip of 2×2 cm (4 cm²) was subjected to folding endurance by folding the film at the same place repeatedly several times until a visible crack was observed, and the values were reported.

 

Surface pH:

The film to be tested was placed in a Petri dish and was moistened with 1 ml of distilled water and kept for 30 sec. The pH was noted after bringing the electrode of the pH meter in contact with the surface of the formulation and allowing equilibrium for 1 min. the average of three determinations for each formulation was done.

 

Disintegration test:

Disintegration time provides an indication about the disintegration characteristics and dissolution characteristics of the film. The require size of film (2×2 cm) was placed in a stainless steel wire mesh containing 25 mL of pH 6.8Phosphate buffer. Time taken by film to break and dissolve was measured as in-vitro disintegration time and in-vitro dissolution time.

 

In vitro dissolution studies:

The simulated salivary fluid (pH 6.8) was taken as the dissolution medium to determine the drug release. The dissolution profile of quick release films of promethazine was carried out using USP type II (paddle apparatus) with 300 ml of simulated salivary fluid (pH 6.8) as dissolution medium maintained at (37 ± 0.5°C). The medium was stirred at 100 rpm. Aliquots (5 ml) of the dissolution medium were withdrawn at every 30 sec time interval and replacing the same amount with the fresh medium. Amount of drug in the withdrawn sample was determined by UV spectrophotometer at 250 nm. Three trials were carried out for all the samples and the average value was taken. The percentage of drug dissolved at various time intervals was calculated and plotted against time. ^[4,13]

 

 

RESULT AND DISCUSSION:

Table 2- Physical characterization of film formulations

 

All the films prepared with different polymer concentration were found to be flexible, smooth, transparent, nonstick and homogeneous. Results showed that more the amount of polymer, higher the thickness values and that weight of the entire film sample in each formulation was uniform.

 

No significant difference in the drug content uniformity. All the films showed good folding endurance greater than 300, indicated that the films have good flexibility.

 

The surface pH was found to be in the range of 6.2 to 7.06, which is close to neutral pH, which indicated that films may have less potential to irritate the sublingual mucosa, thereby they are comfortable.

 

The formulation FA1 shows 51 sec disintegration time. Disintegration time of the films was found to be decreased with increase in the concentration of the HPMC 15cps polymer. 

Dissolution was also found to be improved due to salivary stimulation in the presence of the sweetener (aspartame). ^[9,14]

 

Among all HPMC-PVP films (FA1, FA2 and FA3) extent of drug release was greater in FA3 films. It was observed that with the increased content of PVP, the rate and extent of drug release was faster. This was because of water soluble polymer PVP that result in increase wettability and penetration of water into the film matrices and hence increased diffusion of the drug.

 

Among all HPMC-HPC films (FB1,FB2 and FB3), those formulations with more amounts of HPC i.e., FB3 showed slower release , this may be due to extensive swelling of HPC, which created a high viscosity gel barrier for drug diffusion.

 

 

Table 3- In vitro drug release studies of all formulations

 

Fig.1 Release profile of Promethazine Hydrochloride from formulations FA1, FA2, FA3, FB1, FB2, FB3

 

Fig.2 Comparative study of dissolution profile FA3 and  marketed tablet

 

Among the six formulations (FA1, FA2, FA3, FB1, FB2 and FB3), formulation FA3 and FB1 were found to be best formulations in terms of drug release. ^{10, 12}

 

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