(T1030-12-69) Development of Amorphous Solid Dispersion of Aprepitant Using Sucrose Acetate iso butyrate for Dissolution and Bioavailability Enhancement

Purpose: Aprepitant is a BCS class IV drug with low solubility and low permeability. The bioavailability of aprepitant is the dissolution rate limited by oral administration. Amorphous solid dispersion (ASD) is a formulation approach to improve the solubility of poorly soluble drugs. The objective was to enhance the dissolution and bioavailability of aprepitant using the ASD approach

Methods: ASDs were prepared by solvent evaporation method as per Table 1. Briefly, the drug and the sucrose acetate isobutyrate (SAIB) were dissolved in ethanol by sonication. Surfactant (sodium lauryl sulfate, SLS) was added and sonicated till dissolved. Croscarmellose sodium (CCS) and microcrystalline cellulose (MCC) were added to the drug and polymer solutions with mixing. Solvents were completely evaporated under the hood at room temperature with continuous stirring to form a solid mass. The solid mass was crushed and sieved through the #60 sieve. Physical mixtures (PM) of the drug, SAIB, and other excipients were prepared similar to respective ASDs formulations. Dried powder equivalent to 40 mg drug either filled into capsules or mixed with MGS, and compressed into tablets. The prepared PM and ASD were characterized for physicochemical properties by XRD and DSC, and dissolution. APT optimized SAIB formulations were packed in an HDPE bottle and stored at 25^oC/65% RH and 40^oC/75% RH for six months. Samples at 1M, 2M, and 3M will be withdrawn to test the stability of the prepared formulations. Eight beagle dogs (4 males and 4 females) were used in the pharmacokinetic study of PM and ASD formulation. A single oral dose equivalent to 40 mg APT was given to the beagle dogs. Plasma samples were analyzed by a validated ultra-high performance (UPLC) combined (MS) method.

Results: DSC showed no endothermic peak of the drug in the ASD formulations which confirmed drug transformation into the amorphous form. XRD supported DSC findings as indicating the disappearance of sharp and narrow diffraction peaks of the drug at 6–35 two-theta degrees. The optimized ASD formulation was showing a dissolution % of 93.4% in 2 hours. ASD formulation was stable during the stability period as indicated by no change in DSC and XRD data. Similarly, an insignificant change in the dissolution % of the drug was observed. The Cmax of the ASD optimized formulation PM was 2522.98 ± 390.59 and 1214.19 ± 189.65, respectively. While AUC _(0-t) was 26589.56 ± 2624.45, and 9784.98 ± 722.07, respectively. There was a 2.08 and 2.72-fold increase in the Cmax and AUC _(0-t) for ASD compared to the PM of the same composition.

Conclusion: ASD approach using SAIB can be used to enhance the dissolution and bioavailability of poorly water-soluble drugs with the production of a stable formulation.


ASD formulations composition


Dissolution of ASD optimized formulation


Pk data of ASD optimized formulation and PM