Formulation Effects on the Thermomechanical Properties and Permeability of Free Films and Coating Films: Characterization of Cellulose Acetate Films - Pharmaceutical Technology

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Formulation Effects on the Thermomechanical Properties and Permeability of Free Films and Coating Films: Characterization of Cellulose Acetate Films
The authors investigate the effects of a polyethylene glycol plasticizer and water on cellulose acetate film properties.


Pharmaceutical Technology
Volume 33, Issue 3, pp. 88-100

Results and discussion


Table IV: Cellulose acetate (CA)-free film properties with 0.00% plasticizer (Pz) and 0.00% water in formulations.
CA-free film properties. Effects of plasticizer and water level on CA-free film properties. The CA-free films were opaque, except for the two films that didn't include water in the formulation, which were transparent. Previous studies concluded that water in the film formulation affects the morphology of the film (13, 16). Film properties results are organized in Tables IV, V, and VI according to the water content in the formulations.


Table V: Cellulose acetate (CA)-free film properties with 5.00% water in the formulations.
Modulated differential scanning calorimetry (MDSC) data show that glass-transition temperature (T g ) changed from 191 C without the Pz and water in the formulation to 185 C with the most Pz and the highest water level in the studied range. The small change suggests that PEG 3350 is not a very effective plasticizer for CA films in the studied range. This result is consistent with a previous study (12).


Table VI: Cellulose acetate (CA)-free film properties with 10.00 % water in the formulations.
The value of T 10 (C, N2 purge), at which temperature 10% of the sample weight is lost, represents the thermal stability of the films. The value of T 10 (C, air purge) represents the oxidative stability of the films. Thermogravimetric analysis (TGA) results indicated that Pz and water level didn't have significant influence on the thermal and oxidative stability of the films because the temperatures didn't vary greatly with increasing Pz and water level.


Figure 1: Mechanical strength of cellulose acetate (CA)-free films changes with plasticizer (Pz) and water level. (ALL FIGURES ARE COURTESY OF THE AUTHORS.)
Figure 1 shows the mechanical strength of the CA-free films as it varies with water and Pz level. It is clear that PEG 3350 and water level influence mechanical strength significantly and that PEG 3350 level has the major effect. With increasing PEG level, the films weakened, which was expected because a plasticizer increases polymer chain mobility and decreases mechanical strength. Water functions as a weak plasticizer, so that the film mechanical strength decreased with increasing amount of water in the formulations.


Figure 2: Scanning electron microscopy (SEM) images of the cellulose acetate film without Pz and water. Left: surface image; right: cross-section image.
The significant mechanical strength decrease may also be contributed by the morphology of the films. Figures 2–5 show the scanning electron microscope images of the CA-free films. With increasing Pz level and water level in the formulations, the number and size of the pinholes increased significantly.


Figure 3: SEM images of the cellulose acetate films with 5.00% water in the formulations. Top: surface images; bottom: cross-section images. Left: 0.00% Pz; middle: 1.67% Pz; right: 3.37% Pz.
The percentage of elongation reflects the extent to which the films can be stretched, so that it represents the flexibility of a film. Because a plasticizer increases polymer chain mobility, one would expect Pz level would increase the flexibility of the free films, which increases percent elongation. However, data listed in Tables VI, V, and VI show that the film was more flexible when no Pz and water existed, and not much difference with Pz and water change. This further suggests that PEG 3350 is not an effective plasticizer for the films in the studied range and that bigger and more numerous pinholes with increasing Pz and water made the films less stretchable.


Figure 4: SEM images of the CA films with 10.00% water in the formulations. Top: surface images; bottom: cross-section images. Left: 0.00% Pz; middle: 1.67% Pz; right: 3.37% Pz.
The wettability of a film is represented by the contact angle. A small angle means the film has better wettability. In general, it is known that films plasticized with hydrophilic plasticizer have increased wettability, and the films plasticized with hydrophobic plasticizer have decreased wettability. The data in tables IV, V and VI show that PEG and water level did not affect the wettability of the films in the studied range.


Figure 5: Water vapor transmission rates of CA-free films changes with Pz and water level.
Permeability of a film is a key factor to consider when designing a film formulation. Water vapor transmission rate (WVTR) is a commonly used measurement to determine the permeability of a film. Figure 5 shows the WVTR of CA films changes with Pz and water level. It is not surprising that PEG 3350 alone did not affect WVTR significantly. As discussed previously in this article, PEG 3350 is not a very effective plasticizer for CA in the studied range. However, with the interaction of water and PEG 3350, WVTR increased with PEG 3350 and water level, and significantly increased when water was more than 5% in the formulations. This result can be explained by the morphologies of the films. SEM images show that the number and size of pinholes increased greatly with water and PEG 3350 level (see Figures 2–4).

Acetyl effects on CA-free film properties. CA-398-10TG with acetyl content at 40.3% also was used in the film study to determine how a change in acetyl content over a range of about 1.0% affects film properties. Comparison of the film properties between CA-398-10NF-EP (NF, 39.4% acetyl) and CA- 398-10TG (TG, 40.3% acetyl) suggested that no significant acetyl effect on free-film properties can be observed in the studied range (see Tables IV, V, and VI).

Permeability of CA coating on tablets. CA was coated on model tablets prepared as previously described. The water uptake was measured as a function of time. The water uptake increased linearly with time because of the nature of the POLYOX resin, which will retain water and swell after absorbing water penetrating through the CA film. When the coating film was no longer able to hold the inside pressure, the film ruptured and the experiment was terminated. The slope of the water uptake curve represents water uptake rate (g/min). This value changes with formulation factors such as the plasticizer (Pz) level and water level.

Design expert software (Design Expert V7., Stat-Ease, Inc., Minneapolis, MN) was used to analyze the water uptake data. Based on the data, a model was established to predict water uptake rate. The fitted model is:

Water uptake rate (g/min) =
(3.26145 10-3) + (2.90396 10-5)
PEG – (6.90834 10-5)
PEG2 – (2.35306 10-5) Water + (1.98277 10-6)
Water2 + (9.80461 10-6) PEG Water – (7.15720
10-5 ) Acetyl

in which PEG is the Pz concentration in the formulation as a percentage (0.00–3.37%); Water is the water concentration in the formulation as a percentage (0.00–10.00%); Acetyl is the percent acetyl content of the CA polymer (39.4–40.3%).


Figure 6: Water uptake rate changes with Pz and water level.
The fitted model indicates that an increase in Pz level in the formulation increases water uptake rate, which is also true for water level. PEG is the major influencing factor (see Figure 6).

Figure 7 shows water uptake predicted from the model at Pz = 3.00%, Water = 5.00%, Acetyl = 40.3%, and Acetyl = 39.4%. The difference in the water uptakes between the CAs with these two acetyl levels is 5.7%. The difference in water uptake by acetyl content is calculated by the following equation:


Figure 7: Predicted acetyl effects on water uptake at Pz = 3.00% and water = 5.00%.
Difference in water uptake (%) = (water uptake at acetyl = 39.4%) – (water uptake at acetyl = 40.3%) / (water uptake at acetyl = 39.4%) 100%


Table VII: Water uptake difference between the CAs with two levels of acetyl content (39.4% and 40.3%).
Acetyl effects on the water uptake decreases significantly with increasing Pz and water in the formulations. Table VII lists the difference in water uptake by acetyl content, assuming the coating processing conditions are controlled precisely the same.

When designing a formulation to eliminate the variations from raw materials, it is therefore crucial to understand how formulation factors affect the permeability of the coating film and the release rate of a finished product.


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