(200ah) Effect of Solvent in Strip Film Manufacturing Containing BCS CLASS II Drugs VIA Solution Casting

Oral strip films are an emerging dosage form for drug delivery due to their many advantages over other oral dosage forms, especially in terms of patient compliance and potential for continuous manufacture. [1]. The three primary methods of strip film manufacture are: hot melt extrusion (HME) [2], solution casting [3] and slurry casting [4-6]. This study investigated the effect of solvent on the critical quality attributes of strip films loaded with BCS Class II drugs when using solution casting. The feasibility of solution casting with a binary solvent system (water and organic solvent mixture) was experimentally examined using hydroxypropyl methyl cellulose E15 (HPMC E15) as a film former, glycerin as a plasticizer, fenofibrate (FNB) as a model BCS class II model drug and three organic solvents: ethanol, methanol and acetone. The critical quality attributes that were systematically explored included: content uniformity, mechanical properties (Young’s Modulus, Tensile Strength and Elongation at Break), and dissolution rate of films made using the indicated solvents.

Solution casting was found to have many manufacturing problems starting from polymer solution preparation to drying. Each solvent had a unique impact on the viscosity of the polymer solution. As a result, each solvent formulation required different casting conditions to produce a final product with a consistent thickness. Additionally, the maximum drug loading was limited by the solubility of the solvent. Therefore, at drug loadings above the solubility limit for ethanol and methanol films, a slurry was obtained. Interestingly, phase separation occurred in the precursor made with acetone at high drug loadings (60% FNB in dry film).

All the solvents led to different particle shapes and crystallinity in the dry film. At a drug loading of 10% FNB in the dry film the films made with acetone were the strongest, while methanol led to the weakest films When the drug loading was decreased to 2.5% in the dry film, tensile strength of the films made with acetone were decreased while it was observed to increase for ethanol and methanol films. Although all the solution casted films had different properties, similar dissolution rates were obtained, which were improved compared to films loaded with as-received drug particles. Improved dissolution was attributed to presence of amorphous form of drug, although as expected, significant recrystallization was observed, which continued with time. All the solution casted films also had good drug content uniformity for 10% FNB loading in the film (RSD% < 6), despite re-crystallization of the drug. These results suggest that, although solution casting seems to offer some benefits when creating a dosage form for poorly water soluble drugs, the requirement for careful formulation selection (solvent and polymer type) and unpredictable recrystallization, shows that slurry casting [4-6] is a better candidate for practical implementation.

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