1. A novel self-sealing chewable sustained release tablet of acetaminophen, 2. Development and evaluation of novel itraconazole oral formulations, 3. A novel zero order release matrix tablet.

摘要

This thesis describes evaluation of a novel self-sealing chewable sustained release tablet that can maintain controlled release of drug regardless of compaction, crushing, or chewing. The new formulation contains polyethylene oxide which produces a sealant effect for cracks produced in the polymer coating during compaction. Dissolution studies were conducted and showed that the controlled release properties of the multiple-layered coated beads were present but decreased upon compaction and crushing.;Itraconazole solid formulations were formulated using solid dispersion and solvent/co-cosolvent techniques. Solid dispersion of itraconazole in polyethylene glycol 20000 (PEG 20000) with trisodium citrate gave higher rate of dissolution than dispersion in PEG 20000 alone but didn't have as much effect as desired on rate of drug dissolution. Neutralized acetic acid itraconazole loaded beads exhibited the same in vitro and in vivo release patterns as SporanoxRTM.;Itraconazole liquid formulations were developed and evaluated. Polyethylene glycol 400 (PEG 400) and acetic acid mixtures were found to be a good cosolvent system to solubilize itraconazole and showed good physical stability. Acetic acid, citric acid, and tartaric acid were studied to minimize the amount of PEG 400 needed to produce 1% (w/v) itraconazole solution. Citric acid alone or combined with other agents produced a good physically stable solution; however, these solutions didn't have as much extent as desired on drug dissolution.;Bioavailability and bioequivalence of itraconazole capsule was determined is 13 fasted human volunteers and compared to SporanoxRTM. The 90% confidence intervals for individual percent ratios of the Cmax , AUC0--72 and AUC0--inf were above the range of 80 to 125%, suggesting that these formulations are not bioequivalent. However, this new formulation significantly increased amount of itraconazole absorbed and Cmax of itraconazole in plasma.;A novel controlled release tablet which releases a drug independently of pH and paddle speed, following a lag time and with zero-order kinetics identically to an osmotic pump but using a matrix tablet coated with a diffusional barrier membrane was produced and evaluated. This new matrix tablet generates a diffusional barrier support platform on horizontal surfaces in situ and can be used as an alternative to other zero-order release systems.