Influence of Plasticizer Selection on the Performance of DRUGCOAT® L 100-55 in Enteric-Coated Diclofenac Sodium Tablets: A Comparative Study
ABSTRACT
Enteric coatings are widely used in pharmaceutical formulations to protect drugs from the acidic environment of the stomach or to prevent gastric irritation caused by certain drugs. This study investigates the influence of different plasticizers on the performance of DRUGCOAT® L 100-55, a methacrylic acid copolymer, in enteric coating applications. Core tablets of Diclofenac sodium, a non-steroidal anti-inflammatory drug (NSAID) known for its gastric irritant properties, were prepared via wet granulation and coated with aqueous dispersions of DRUGCOAT® L 100-55 containing various plasticizers. Dissolution studies were conducted in accordance with the USP monograph for delayed-release Diclofenac sodium tablets. The results demonstrate that the choice of plasticizer significantly impacts the drug release profile, with water-soluble plasticizers such as PEG 400 and PEG 6000 acting as pore formers, leading to higher acid uptake and slower drug release. In contrast, hydrophobic plasticizers like diethyl phthalate (DEP) and triacetin did not exhibit pore formation. Among the tested plasticizers, triethyl citrate (TEC) provided the most optimal results, suggesting that citrate ester plasticizers are well-suited for acrylate-based polymers. This study underscores the importance of plasticizer selection in modulating drug release profiles in enteric-coated formulations.
INTRODUCTION
Enteric coatings are polymer-based barriers applied to oral medications to prevent their dissolution or disintegration in the acidic environment of the stomach. These coatings are particularly important for drugs that are unstable at low pH or those that can cause gastric irritation. The term “enteric” refers to the small intestine, and enteric coatings are designed to ensure that the drug is released only after reaching the higher pH environment of the small intestine. This pH-dependent release is typically achieved using polymers that remain stable in the acidic stomach but dissolve rapidly at the more neutral pH of the intestine.
Methacrylic acid copolymers, such as DRUGCOAT® L 100-55, are among the most commonly used polymers for enteric coatings due to their pH-dependent solubility properties. Diclofenac sodium, a widely used NSAID, is known to cause gastric irritation and is therefore often formulated with an enteric coating to minimize adverse effects. The performance of enteric coatings can be influenced by various factors, including the type of plasticizer used in the coating formulation. Plasticizers are essential components that improve the flexibility and film-forming properties of the polymer, but their solubility and interaction with the polymer can significantly affect the drug release profile.
This study aims to evaluate the impact of different plasticizers on the performance of DRUGCOAT® L 100-55 in enteric-coated Diclofenac sodium tablets. The findings will provide insights into the selection of appropriate plasticizers for optimizing drug release in enteric-coated formulations.
MATERIALS AND METHODS
Materials
The following materials were used in this study:
- DRUGCOAT® L 100-55 (Vikram Thermo (India) Ltd., India)
- Plasticizers: Triethyl citrate USP, Diethyl phthalate USP, Triacetin USP, PEG 6000 USP, PEG 400 USP
- Excipients: Talc USP, Titanium dioxide USP
- All other reagents and solvents were of analytical grade.
Methods
Preparation of Core Tablets
Core tablets of Diclofenac sodium were prepared using the wet granulation method. The composition of the core tablets is provided in Table 1.
| Table 1. Composition of core tablet of Diclofenac sodium | |||
| INGREDIENT | SPECIFICATION | QUANTITY/TAB | |
| A. Dry mix | |||
| Diclofenac sodium | USP | 50.0 mg | |
| Micro crystalline cellulose, pH 101 | USP | 68.5 mg | |
| Lactose | USP | 68.5 mg | |
| Cross povidone | USP | 02.5 mg | |
| B. Binder | |||
| PVPK-30 USP | USP | 4.0 mg | |
| Demineralized water | USP | q.s. | |
| C. Lubrication | |||
| Colloidal Silicon Dioxide USP | USP | 2.0 mg | |
| Magnesium stearate USP | USP | 2.0 mg | |
| Cross povidone USP | USP | 2.5 mg | |
| TOTAL | 200 mg | ||
Preparation of Enteric Coating Dispersion
The enteric coating dispersion was prepared by accurately weighing the ingredients as per Table 2. DRUGCOAT® L 100-55 was added to demineralized water under continuous stirring, followed by neutralization with 1 N NaOH solution. After 15 minutes, the plasticizer was added, and the mixture was further stirred. Talc and titanium dioxide were then suspended in the dispersion, and the mixture was stirred for an additional 40 minutes before being passed through a #200 nylon mesh.
| Table 2. Composition of enteric coating dispersion | |||||
| INGRIDIENTS | F1 | F2 | F3 | F4 | F5 |
| DRUGCOAT® L 100-55 | 60 | 60 | 60 | 60 | 60 |
| 1 N NaOH | 20 | 20 | 20 | 20 | 20 |
| Tri ethyl citrate | 7.2 | – | – | – | – |
| Diethyl phthalate | – | 7.2 | – | – | – |
| Triacetin | – | – | 7.2 | – | – |
| PEG 6000 | – | – | – | 7.2 | – |
| PEG 400 | – | – | – | – | 7.2 |
| Talc | 18 | 18 | 18 | 18 | 18 |
| Titanium Dioxide | 6 | 6 | 6 | 6 | 6 |
| Demineralized water | 345 | 345 | 345 | 345 | 345 |
Coating of Core Tablets
The core tablets were coated with the prepared enteric coating dispersions using an auto coater (Chitra Machineries Pvt. Ltd., CMPL-TCS-12″). The coating process was optimized to achieve a 6% theoretical polymer weight gain, with samples withdrawn at 5% weight gain for comparative analysis. The processing parameters for the coating process are detailed in Table 3.
| Table 3. Processing parameter for coating in Auto coater | |
| PARAMETER | VALUE |
| Inlet temperature | 53˚-56˚ C |
| Product temperature | 40˚-42˚ C |
| Inlet / Outlet Blower | 550 rpm |
| Atomization air | 1.0 bar |
| Feed rate | 3-6 gm/min |
EVALUATION
Acid Uptake Test
The acid uptake test was conducted to evaluate the integrity of the enteric coating in acidic conditions. Six coated tablets were individually weighed and placed in a disintegration basket, which was immersed in 0.1 N hydrochloric acid for 2 hours. The tablets were then dried and reweighed to determine the percent weight increase, which was reported as percent acid uptake.
In Vitro Dissolution Study
The drug release profile of the enteric-coated tablets was evaluated using a dissolution apparatus according to the USP monograph for delayed-release Diclofenac sodium tablets. The absorbance of the samples was measured at a wavelength of 276.2 nm to determine the drug release rate.
RESULTS AND DISCUSSION
Acid Uptake Analysis
The acid uptake results (Figure 1) demonstrated significant variations among formulations based on plasticizer type. Formulations containing hydrophilic plasticizers (PEG 400 and PEG 6000) exhibited higher acid uptake compared to hydrophobic plasticizers (triethyl citrate, diethyl phthalate, and triacetin). This suggests that water-soluble plasticizers act as pore formers, compromising the coating integrity in acidic media.
Drug Release Profiles
The dissolution profiles of Diclofenac sodium from enteric-coated tablets (5% and 6% weight gain) were evaluated in two stages: acid resistance (0–2 hours, pH 1.2) and drug release in buffer (pH 6.8). The results demonstrated significant differences in release kinetics based on plasticizer type and coating thickness.
All formulations exhibited good gastric protection, with 0% drug release after 2 hours in acidic medium, complying with USP requirements for delayed-release dosage forms.
The drug release profiles in the intestinal pH environment revealed significant differences among the plasticizer formulations. Triethyl citrate consistently demonstrated the fastest release, rapidly achieving substantial drug dissolution within the first 10 minutes and approaching complete release by 30 minutes, regardless of coating thickness. In contrast, diethyl phthalate showed moderately slower initial release but still reached near-complete dissolution within the same timeframe. Triacetin exhibited an interesting dependence on coating weight, with the thinner coating displaying the most rapid early release among all formulations, while the thicker coating showed noticeably delayed onset. The PEG-based plasticizers produced the most prolonged release profiles, with substantially slower initial dissolution compared to the other plasticizers, though eventually reaching similar completion levels. These findings clearly highlight how plasticizer selection critically governs the drug release performance, with hydrophilic plasticizers like PEGs creating a more sustained release pattern, while hydrophobic alternatives, particularly triethyl citrate, promote faster and more consistent drug liberation in the intestinal environment.
CONCLUSION
The selection of plasticizers in enteric coating formulations is a critical factor that can significantly impact the performance of the coating. This study demonstrates that water-soluble plasticizers like PEG 400 and PEG 6000 can act as pore formers, leading to increased acid uptake and slower drug release. In contrast, hydrophobic plasticizers such as diethyl phthalate and triacetin do not exhibit this effect. Among the tested plasticizers, triethyl citrate provided the most optimal results, suggesting that citrate ester plasticizers are well-suited for use with acrylate-based polymers like DRUGCOAT® L 100-55.
These findings underscore the importance of careful plasticizer selection in the development of enteric-coated formulations. By modulating the type and concentration of plasticizers, it is possible to achieve the desired drug release profile, ensuring both the efficacy and safety of the medication.