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Mouth dispersing films; Ranolazine; Polymers; Plasticizer; Solvent casting method

Introduction

The majority of pharmaceutical researchers are mostly focused on the oral dosage form since it provides a rapid drug release and has a quick onset of action. Mouth Dissolving Films (MDFs) are a unique and state-of-the-art medicine delivery system that increases patient compliance. MDFs systematically administer the medication by the buccal or sublingual routes in addition to providing local action. MDFs are a thin film that, when placed on the tongue, quickly becomes moistened from saliva. The film subsequently dissolves and disintegrates in a matter of seconds, allowing the medicine to be absorbed. MDFs have an advantage over capsules and other dosage forms since the film dissolves quickly and exhibits an immediate commencement of action. Owing to increased blood flow and the oral mucosa's 4-1000-fold higher permeability than skin, MDFs boost bioavailability. minimizes first pass metabolism and shortens the onset time. Since it enhances drug efficacy, flexibility, disintegration, and dissolution, fast dissolving drug delivery is the most sophisticated form [1]. Fear of choking on dosage forms is a common reason why many elderly and pediatric patients are reluctant to receive solid preparations. 26% of patients reported having trouble swallowing medications, according to one study. After taste and surface form, the most common complaints were over tablet size [2].

A compound of acetanilide and piperazine with anti-ischemic qualities is ranolazine. The USFDA approved it for the treatment of angina pectoris in 2006. It reduces intracellular calcium levels by blocking sodium channels, which in turn causes the heart muscle's (myocardium) tension to decrease.

Researchers refer to the quickly dissolving dosage forms by a number of names, including melt-in-the-mouth, quick-disintegrating, oral-disintegrating, and mouth dissolve [3].

Materials

Ranolazine was obtained as a gift sample from Ajanta pharmaceuticals, bharuch, GujratGujrat, India. HPMC E15, PVA, PEG-400, Sodium Starch glycolate. Citric acid, mint was obtained from Research lab.

Methods

Preparation of mouth dissolving films (MDFs)

Using the solvent casting approach, MDFs were created [4]. This technique involves immersing polymers, including PVA and HPMC E15, for an entire night. After adding sodium starch glycolate and all additional excipients—like aspartame, PEG 400, citrus flavor, and citric acid—to the polymer solution, it was agitated for an hour at 1000 rpm. After dissolving in a little amount of methanol, ranolazine was added to the polymer solution and swirled for 30 minutes at 100 rpm.  After that, the obtained solution is set aside for a few minutes in order to release the trapped air bubbles. The solution was placed in a glass Petriplate (with a 10 cm diameter). and allowed to dry at 45ºC for four to five hours. After carefully removing the film from the petriplate, it was inspected for any defects and sliced into the appropriate dimensions to provide each film with the equivalent dosage of 2 x 2 cm². The produced films were placed in aluminum foil bags and kept between 30 and 35 percent relative humidity in a desiccator [5].

Results and Discussion

Characterization of Ranolazine (Table 1)

Table 1:Description of Ranolazine.

Solubility

Ranolazine dissolved readily in both ethanol and methanol.

Melting point

Ranolazine's melting point was discovered to be 121°C. Consequently, it shows how pure the sample is.

Determination of λ max of Ranolazine

It was discovered that ranolazine's λ max was 272 nm (Figure 1).

Figure 1: UV Spectrum of Ranolazine.

Standard calibration curve of Ranolazine

Standard calibration curve of Ranolazine in phosphate buffer

In phosphate buffer with a pH of 6.8, ranolazine exhibited maximum absorption at 272 nm. A standard curve was created by measuring the absorption of diluted stock solutions (1,2,4,6, 8, 10 μg/ml) at this wavelength [6] (Table 2 and Figure 2).

Table 2: Standard calibration curve of Ranolazine in phosphate buffer.

Figure 2: Calibration curve of Ranolazine.

The standard calibration curve for ranolazine parameters in phosphate buffer is presented

Drug excipients compatibility studies by IR spectroscopy

Ranolazine's infrared spectrum captured on an FTIR-4100 in Jasco, Japan using a KBr pellet. The corresponding assignments for the infrared frequencies are listed below [7].

IR Peaks of various functional groups of ranolazine (Figure 3, Figure 4, Figure 5 and Figure 6)

Figure 3: IR spectrum of Ranolazine.

Figure 4: IR Spectra of Ranolazine with HPMC E15.

Figure 5: IR Spectra of Ranolazine with HPMC E15.

Figure 6: IR Spectra of Ranolazine With PEG 400.

Dose calculation

The drug dose dictated how much drug to be put into the film, and the glass plate's area dictated how much drug should be loaded into it.

The plate's diameter is 10 cm.

Plate area = πr² = 78.5 cm²

Total number of 4 cm² films on the plate = 78.5/4 s = 19.62

The medication content of each film is 20 mg.

Each plate has to contain 19.62 x 10 = 392.4 mg of medication (Table 3 and Figure 7).

Table 3: Formulation of mouth dissolving film.

Figure 7: Picture of mouth dissolving film (F3).

7.5 Evaluation of formulation F3

1. A) Appearance & Tack test

Analyzing Films Made for Formulation Design The tack test and appearance were examined in the table that is as follows [8] (Table 4).

Table 4: Evaluation for film forming capacity, tack test and appearance of film.

1. B) Thickness of mouth dissolving film

A screw gauge with a resolution of 0.1 mm and a range of 0-10 mm was used to measure the thickness of the film. After ensuring that the pointer was set to zero, the MDF sample equal to the medicine dosage was taken, the thickness gauge's anvil was lifted, and the MDF was inserted. The MDF was placed at anvil and the dial's reading was recorded. The mean thickness was determined by averaging the three values [9] (Table 5).

Table 5: Thickness of mouth dissolving film.

1. C) Weight variation of strip

By using the solvent casting procedure, mouth dissolving films were created. After cutting each 2 sq. cm film from the cast, the weight variation was measured, and the mean and standard deviation of the data were determined (Table 6).

Table 6: Weight variation of mouth dissolving film.

1. D) Folding endurance

The ability of three films from each batch to fold repeatedly was tested by folding a single film at the same location for 200 times, or until it broke or folded, which is deemed sufficient to demonstrate good patch qualities (Table 7).

Table 7: Folding endurance of mouth dissolving film.

A range of 150-200 folds was found to yield a high enough score for folding endurance. This suggests the appropriate flexibility of the required strip.

1. E) Surface pH

To find the pH, dissolve one oral film in 10 milliliters of distilled water. Then, measure the pH of the resulting solution by touching the electrode of a pH meter to the film's surface and letting it acclimate for a minute. Every calculation was done three times (Table 8).

Table 8: Surface pH of mouth dissolving film.

1. F) Tack test

The strength with which a strip sticks to a piece of paper or an accessory after being pressed into contact with it is known as its tack. These observations are recorded in Table 9.

Table 9: Content uniformity of mouth dissolving film.

1. H) in-vitro Disintegration time (Table 10)

Table 10 : In- vitro Disintegration time of mouth dissolving film.

Measurements of the in-vitro disintegration times for each batch revealed that the disintegration times increased with polymer concentration.

1. In-vitro dissolution study (Drug release study) (Table 11, Table 12 and Figure 8)

Table 11: In-vitro dissolution study of F1 toF4.

Table 12: In-vitro dissolution study of F5 toF8.

Figure 8: Drug release profile of batch F1 to F8.

As can be seen from the preceding in-vitro dissolution analysis of Formulation batches F1-F8, of which Formulation F3 showed that 94.34% of the medication was released in 5 minutes in simulated saliva made of phosphate buffer saline solution. Due to its rapid commencement of action, it is most desirable for mouth dissolving films to dissolve quickly; hence, research reveals that these films dissolve quickly.

1. Stability study

The stability study's findings showed that the medication product complies well with the suggested stability requirements. According to the data, there hasn't been any noticeable change in either the physical or chemical properties, meaning that the formulation will stay effective and high-quality for the duration of its suggested shelf life (Table 13).

Table 13: Stability study of mouth dissolving film.

Conclusion

By creating MDFs of ranolazine, the current study's goal has been accomplished. Solvent casting has been successfully used to create ranolazine mouth dissolving films (MDFs). In comparison to other formulations, the F3 formulation releases the medication immediately, according to the in vitro studies. As no appreciable variations in drug release, content homogeneity, or other physical attributes were noticed, the formulation F3 was determined to be stable. These current findings imply that oral thin films containing ranolazine dissolve in less than a minute, suggesting that they may be helpful in treating angina, dysphasia or aphasia patients, elderly patients who refuse to take pills and other conditions.

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