This work is part of an overall objective of being able to create patient compliant drug loaded thin polymeric films that are uniform in drug content or where the amount of drug varies by a minuscule amount and has negligible effects to the drug dosage. The goal of this specific work is to compare the critical material attributes (CQAs) of strip-films, loaded with a BCS Class II drug, produced via solution casting and slurry casting. As-received fenofibrate (FNB) was used to prepare slurry casted films as the baseline/control for CQAs. The primary difference between the two techniques is that the drug is fully dissolved in solution casting, as opposed to slurry casting where the drug is suspended in the polymer solution as nanoparticles or micronized coated particles. Solution casting may increase the dissolution rate of the poorly water-soluble drug producing amorphous particles while in the slurry casting introducing nano-sized or micon-sized drug particles into water based system increases the dissolution rate with highly increased total surface area of the drug. For both methods, FNB was used as the model poorly water-soluble drug, hydroxypropyl methylcellulose (HPMC) E-15 as the film-former, and glycerin was used as the plasticizer. For solution casting, a binary solvent system consisting of 1:4 ratio of deionized water to organic solvent was used. Three organic solvents were evaluated: methanol, ethanol, and acetone. FNB nanosuspensions were prepared via wet stirred media milling (WSMM). Micronized coated FNB particles were prepared via fluid energy milling (FEM). Mechanical attributes (Youngâs Modulus, tensile strength, and elongation at break), dissolution rate of the drug, content uniformity, and crystallinity of the drug in each film were evaluated as the CQAs of the strip-films.
All the films exhibited similar dissolution profiles of films loaded with nanosuspension and solution films. While as was expected, the films loaded with micronized coated powder released slower. Overall, the film CQAs containing the drug nanosuspension and micronized coated powder were found to be superior. Those films had better drug content uniformity, higher elongation at break, and long-term stability; all of these are desirable CQAs. Interestingly, solution casted films had acceptable drug content uniformity, despite re-crystallization of the drug, and visual non-uniformities. Unfortunately, solution casting had a host of manufacturing problems such as longer drying time due to need for lower maximum drying temperatures in order to avoid excessive bubble and defect formation, unpredictable drug particle re-crystallization and different drug particle shapes that change with time, and most importantly, burden of formulation development that also includes selection of solvent that must be tailored to a specific drug.
