Purpose: Ethyl Cellulose (EC) coated pellets are frequently used for oral controlled drug delivery. Hydrophobic plasticizers such as HPC are typically added to ensure film-formation, and hydrophilic excipients such as PVA & PEG are required to ensure drug release. This research evaluates whether the water-soluble plasticizer, triethyl citrate (TEC) and Triacetin can plasticize EC while simultaneously contribute to drug release through pore-formation.
Methods: Ethyl cellulose films containing 30%, 40% and 50% w/w TEC or Triacetin were prepared by pouring aqueous dispersions of plasticized ethyl cellulose into aluminum pans and drying in the oven for 24-48 hours. Differential Scanning Calorimeter (DSC Q100) was used to evaluate the glass transition temperature (Tg) of the films. Mechanical testing (Instron 3360) was performed to evaluate tensile strength, percent elongation, and young modulus. EC-TEC or Triacetin coated acetaminophen pellets were manufactured using a Wurster Coating drug layering process where solution/suspension of drug is layered onto the inert sugar spheres followed by the rate controlling polymer layering to obtain control release function. Compendial dissolution methodology was used to determine drug release from the coated pellets.
Results: With the increase in the TEC concentration, the effect on the mechanical and thermal properties of the prepared polymeric film was constant attributing to complete saturation of the polymeric film at the plasticizer concentration used. Figure 1 below the shows the comparative transition glass temperature and stress and strain analysis of the films prepared using different TEC concentrations.
It should be noted that glass transition temperature of pure EC polymer and commercially available aqueous ethyl cellulose dispersion (Aquacoat ECD) is approximately 120ºC² and 70ºC³ respectively. As evident from Figure 1 on previous page, the plasticization of the aqueous EC dispersion with Triethyl Citrate had significant impact on the glass transition temperature and thermal properties of the polymeric films as indicated by the glass transition temperature and tensile strength, elongation and young modulus results generated for the control polymeric film prepared without any plasticizer versus the polymeric film prepared with 30% w/w concentration of TEC. However, increase in the TEC w/w concentration from 30% to 40% and 50% did not attributed to any significant changes in terms of glass transition temperature and evaluated mechanical properties of the polymeric films.
The release of APAP was controlled with the application of hydrophilic/water soluble plasticizers as pore formers. In addition, increasing the coating weight gain decreased the release rate of the drug. The use of TEC and Triacetin as pore-former resulted in approximately 100% drug release over the period of 12 hours with the drug release profile like using a traditional pore-formers i.e., HPMC and PVA & PEG. In addition, the use of the hydrophilic/ water-soluble plasticizers as pore-formers at higher concentration resulted in elimination of required thermal/curing step, when using traditional pore-formers. This can be attributed to the fact that use of the hydrophilic/water soluble plasticizers at higher level can aid in the polymer particle coalescence process resulting in complete film formation.
Conclusion: CONCLUSION: The use of the water-soluble plasticizers provides an alternative to widely used traditional water-soluble polymers as pore-formers and streamlines the formulation and manufacturing process of the Controlled release pellets. This study supports that with a proper composition of a hydrophilic plasticizer, it is possible to develop a controlled release drug delivery system with optimal drug release
Sriramakamal Jonnalagadda– Director and Professor, Philadelphia College of Pharmacy, Pennsylvania