(738d) Impact of Dry Coating on Dissolution Profile of Micronized BCS Class II Drugs: Influence of Coating Material Hydrophobicity

Sangah Kim, Liang Chen, Kuriakose Kunnath, Ecevit Bilgili, Rajesh Dave^*

BCS Class II drugs exhibit poor aqueous solubility, which leads to slow and poor absorption through the gastrointestinal tract and in turn inadequate bioavailability. One way to overcome this issue is the micronization of drug particles, thus enhancing their surface area and in turn the dissolution rate¹. However, such fine particles tend to agglomerate during the processing and storage, which negates the benefits of micronization^2-5. Simultaneous micronization–dry coating and dry coating of micronized drug particles have been shown to be effective for reducing the extent of agglomeration and increasing the surface area of drug particles^4,5. While previous investigations focused on the impact of dry coating on drug particle agglomeration and dissolution enhancement, the impact of coating material on the surface hydrophobicity of drug particles has not been examined. Hence, the current study aims to fill this gap by examining the impact of hydrophobicity of the applied dry-coating material on the dissolution rate of selected BCS class II drugs. Griseofulvin (d₅₀ of 10 µm) and Ibuprofen (d₅₀ of 20 µm) were selected as model drugs. Each drug was dry coated with either hydrophilic (A200) or hydrophobic (R972P) fumed silica via LabRAM, and theoretical calculations were used to select the amount of coating material for achieving 0-100% surface area coverage (SAC). De-ionized water was used as the dissolution medium to investigate the effect of dry coating. USP IV dissolution test with USP <711> protocol was conducted on each formulation. Collected dissolution data was then fitted by the Peppas model to estimate its parameters, i.e., k and n (R² values close to 1). Relative hydrophobicity of different formulations was evaluated by using the modified Washburn method with pre-saturated de-ionized water as the wetting liquid. Using the slope of the square of liquid mass penetrated vs. time curve, we calculated the wetting enhancement factor⁷: cosθ_c/cosθ_uc where cosθ_c and cosθ_uc stand for the cosine of the advancing contact angle of the coated and uncoated drug powder, respectively. This factor is greater than 1 when the coating enhances wettability of the drug powder.

Compiled results from dissolution study and wettability testing show that the hydrophobicity of the applied coating material significantly affects the wettability of the drug powder and thus the dissolution profiles. In general, for both drugs, hydrophobic coating material led to slower drug release than the hydrophilic coating material. The enhancement with coating depended on the type and SAC. On the other hand, the impact of dry coating on the wettability and dissolution of different drugs was markedly different. Surface wetting rate was the dominant factor dictating the dissolution rate of dry coated Griseofulvin. The higher the wettability enhancement of Griseofulvin, as quantified by the higher wetting effectiveness factor cosθ_c/cosθ_uc , the faster the dissolution (higher k of the Peppas model). When coated with R972P, micronized GF exhibited slower dissolution, and this impact got stronger with an increase in SAC of R972P. However, for Ibuprofen, the analysis revealed a more convoluted relationship of dissolution profiles with the SAC and type of coating material. Surprisingly, the 50% SAC with R972P coating led to wettability enhancement and faster drug dissolution despite the hydrophobicity of the coating material. We hypothesize that the impact of both agglomerate size and wettability after dry coating are important factors that govern the dissolution rate of Ibuprofen. This hypothesis was tested with QICPIC, a dynamic particle image analyzer, which does not cause significant dispersion of agglomerates during the measurement, thus yielding information about the inherent agglomerate particle sizes in the samples. Overall, this study has demonstrated the importance of coating material hydrophobicity and SAC, through their impact on wettability and extent of drug particle agglomeration, in the dissolution of coated, micronized drug particles. The fundamental understanding of the mechanisms controlling the drug release from coated, micronized drug particles will ultimately enable rational design of solid oral dosages using micronized BCS Class II particles.

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