Reproducible delivery of drugs through bioencapsulation in cellular carriers is severely limited by biovariability in cellular carriers and effects of decisive formulation variables. Surmounting the constraints in reproducible results, our work explores optimization methodology for precise and reproducible cellular bioencapsulation technology for poorly water soluble drug. Active-dried baker’s yeast cells were selected as cellular carriers for poorly soluble antimycotic agent itraconazole (ITZ). Pre-treatment of yeast cells with various techniques exhibited substantial augmentation in bioencapsulation efficiency (%BE). Sequentially optimized values of formulation variables like bioencapsulation temperature (40-50°C), stirring rate (350?rpm) and time (5?h) exhibited highest %BE with desired reproducibility. In comparison with marketed product, bioencapsulated itraconazole demonstrated marked increase in solubility with more than 70% release in 10?min. Compression pressure equivalent to tablet hardness of 2.0-3.5?kg/cm2 was optimum to maintain integrity of biocapsules. Resulting biocapsules exhibited safe residual solvent content, inertness for fermentation ability and excellent stability at accelerated conditions. © 2011 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.