Determination of Fast Dissolve Oral Film Dissolution Rate via Conductivity
E. Jayjock, Robert Schmitt, Chiling Chien, Gloria Tirol
The Dow Chemical Company, Midland, MI 48674
Poster presented at the 2005 Annual Meeting and Exposition of the American Association of Pharmaceutical Scientists Nashville, Tennessee November 610, 2005
*Trademark of The Dow Chemical Company
Determination of Fast Dissolve Oral Film Dissolution Rate via Conductivity
E. Jayjock, Robert Schmitt, Chiling Chien, Gloria Tirol
The Dow Chemical Company, Midland, MI 48674
Introduction
In the past 5 years several personal care products formulated in quick-release film form have entered the marketplace, of which fast-dissolve breath fresheners were the first. Since then, a series of over-thecounter medicines and vitamins have entered the market in film form. Recently, fast-dissolve oral strips appear to have found a niche in the pediatric market. As this new market continues to define itself it is necessary to develop tests to quantify the performance and quality of these products. The classic USP II dissolution rate determination for tablets was designed to measure dissolution over 10 or more minutes. However, the fast-dissolve oral films completely dissolve in as little as 1 minute. The majority of oral films on the market today contain ionizable components. This work presents a method for highresolution monitoring of the dissolution of fastdissolve oral films by measuring conductivity of the dissolution medium.
Equipment
Equipment includes the following. A diagram is shown in Figure 1. Variable speed stirrer motor: capable of 250 rpm Analytical balance (medium weight): capable of weighing to the nearest 0.01 g and having a range no less then 400 g Low-form beaker: 3 x 800 mL Impeller: 2-inch diameter, 1 blade (stainless steel or Monel metal) Conductivity probe: capable of measuring conductivity to 0.1 Siemens (Hanna 8033 Conductivity meter) Laboratory equipment stand Double-sided clear tape: -inch-wide External stand with clip to hold conductivity probe Scissors Stopwatch or timepiece with a second hand
Figure 1. Diagram of equipment set-up.
Materials and Methods
Several brands or types of fast-dissolve oral films were purchased. The polymers and salts in each film were determined from the label.
Table 1. Ingredients of fast-dissolve oral films used in dissolution experiments (determined from labels). Product A Polymers Hypromellose (HPMC), hydroxypropyl cellulose (HPC) Pullulan HPC, HPMC, microcrystalline cellulose (MCC) Pullulan Polyethylene oxide, polydextrose Sodium alginate Carboxymethyl cellulose modified pectin Pectin Salts Potassium acesulfame Potassium acesulfame Diphenhydramine HCl Potassium acesulfame Magnesium stearate Sodium alginate Acesulfame potassium Potassium stearate
Conductivity Probe
Impeller
B C D E F G H
Film
Film Preparation
One side of the film is adhered to the doublesided tape, and the double-sided tape is cut to the dimensions of the film (Figure 2).
Figure 2. Diagram of prepared film.
Figure 3. Conductivity dissolution profiles for Film D.
120 Potassium Acesulfame Released (%)
100
80
Film Double-sided tape
60 Run 1 Run 2 Run 3
40
Test Procedure
1. Fill a clean beaker with 300.00 g (0.05 g) of deionized water. 2. Test the conductivity of the water to establish background value. 3. Adhere the film inside the dry, clean 800-mL beaker so that the center section is even with (or slightly below) the 100-mL line of the beaker. Arrange the conductivity probe and impeller in the beaker. 4. As quickly as possible pour the 300 mL of water in the beaker containing the film, impeller, and conductivity probe. When the water completely covers the film, start the timer (approximately 3 s). Then restart the impeller, stirring at 250 rpm. 5. Take a data point every 10 s for the first minute. Then take data as appropriate.
20
0 0 1 2 3 4 Time (min) 5 6 7
Figure 4. Conductivity dissolution profiles for various films.
120 Active Ingredient Released (%) 100 80 60 40 20 0 0 1 2 3 4 Time (min) 5 6 7 Film A, N = 2 Film G, N = 2
Data Reduction
If the amount of ionizable species in these films is unknown, as was the case in these experiments, the final conductivity cannot be known before the test is done. Therefore the test is run until the rate of change of the conductivity falls to less then 0.15 S/min. The data are then scaled considering the background is 0% and the point at which the rate falls below 0.15 S/min is 100%. For each film, multiple tests are run and a single curve and error are generated from the data. For the comparison of one film versus another, the time it takes for 50% and 75% release is used.
The times to 50% and 75% dissolution provide a good comparison of the various dissolution rates for these commercial films (Figure 5).
Figure 5. Time to 50% and 75% dissolution for various films.
7 6 5 Time (min)
Results and Discussion
Figure 3 shows the raw data for Film D. The test method provides very reproducible data and captures the release profile during the critical first minute of release. Films A and G were found to have the most extreme dissolution profile (Figure 4). Film G underwent a very slow, almost linear release, whereas Film A rapidly disintegrated.
4 3 2 1 0 A
T50 T75
Conclusions
The conductivity method provides an experimental strategy for benchmarking the dissolution performance of orally dissolvable films on a time scale consistent with the dissolution time in vivo. The system has the advantage of being simple to run and uses common laboratory equipment. In addition to being a metric for rate of dissolution in the mouth, it is likely that the rate of dissolution has a strong effect on the tactile feel of the film in the mouth. Therefore this test may also yield some information on the quality of the customers experience.
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