Poorly water-soluble drugs such as Camptothecin Analog (CA) offer challenges in developing a drug product with adequate bioavailability. The objective of the present study was to develop a tablet dosage form of CA incorporating drug nanoparticles to increase its saturation solubility and dissolution rate for enhancing oral bioavailability. The bioavailability of CA is dissolution limited following oral administration. To enhance bioavailability and overcome variability in systemic exposure, a nanoparticle formulation of CA was developed. Drug nanoparticles were prepared using a wet bead milling technique. The milled nanosuspension was converted into solid intermediate using a spray granulation process. The nanosuspensions were characterized for particle size before and after spray granulation. The spray granulated nanoparticles were blended with excipients for tableting. The saturation solubility and dissolution characteristics of the nanoparticle formulation were investigated and compared with micronized and as-is drug formulations to ascertain the impact of particle size on drug dissolution. The drug nanoparticles were evaluated for solid-state transitions before and after milling using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The results demonstrated that tablet formulation incorporating drug nanoparticles showed significantly faster rate of drug dissolution in a discriminating dissolution medium as compared to micronized drug formulation. There was no effect on solid-state properties of drug on milling. Systemic exposure studies in rats indicated a significant increase in the rate and extent of drug absorption with nanoparticle formulation. The manufacturing process used is relatively simple and scalable indicating general applicability to enhance dissolution and bioavailability of poorly soluble compounds.
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