• Journal of Pharmaceutical Investigation
• /
• v.31 no.1
• /
• pp.19-25
• /
• 2001

The purpose of this study was to use a ternary polymeric matrix system for high drug loading of a highly soluble drug for controlled release delivery. The controlled drug delivery of diltiazem HCl (solubility > 50% in water at $25^{\circ}C$) with high loading dose (the final loading dose of drug was 34%) from a ternary polymeric matrix (gelatin, pectin, HPMC) was successfully accomplished. This simple monolithic system with 240 mg drug loading provided near zero-order release over a 24 hour-period by which time the system was completely dissolved. The release kinetics of diltiazem HCl tablet with high loading dose from the designed ternary polymeric system was dependent on the ratios of HPMC : pectin binary mixture. The release rate increased as pectin : HPMC ratio were increased. Swelling behavior of the ternary system and the ionic interaction of formulation components with cationic diltiazem molecule appear to control drug diffusion and the release kinetics. Comparable release profiles between commercial product and the designed system were obtained. The binding study between gelatin with diltiazem HCl showed the presence of two binding sites for drug interaction with subsequent controlled diffusion upon swelling. This designed delivery system is easy to manufacture and drug release behavior is highly reproducible and offers advantages over the existing commercial product.

• Archives of Pharmacal Research
• /
• v.26 no.7
• /
• pp.569-574
• /
• 2003

Controlled-release amitriptyline pellets (ATP) were formulated and its oral bioavailability was assessed in human volunteers after oral administration under fasting conditions. Core pellets were prepared using a CF granulator by two different methods (powder layering and solvent spraying) and coated with Eudragit RS or RL 100. Physical characteristics and dissolution rates of core pellets and coated pellets were evaluated to optimize the formulation. Powder layering method resulted in a better surface morphology than solvent spraying method. However, physical properties of the products were poorer when prepared by powder layering method with respect to hardness, friability and density. The dissolution profile of amitriptyline coated with Eudragit RS 100 was comparable to that of commercially available amitriptyline enteric-coated pellets ($Saroten^{\circledR}$ retard). After the oral administration of both products at the dose of 50 mg, the mean maximum concentrations ($C_{max}$) were 36.4 and 29.7 ng/mL, and the mean areas under the concentration-time curve ($AUC_{0-96}$) were 1180.2 and 1010.7 ng.h/mL for ATP and Saroten retard, respectively. The time to reach the maximum concentrations ($T_{max}$) was 6 h for both formulations. Statistical evaluation suggested that ATP was bioequivalent to Saroten retard.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.10
• /
• pp.5797-5804
• /
• 2013

In order to enhance the bioavailability of curcumin its conjugates with piperic acid and glycine were synthesized by esterifying the 4 and 4' phenolic hydroxyls, the sites of metabolic conjugation. Antiproliferative and apoptotic efficacy of synthesized conjugates was investigated in MCF-7 and MDA-MB-231 cell lines. $IC_{50}$ values of di-O-glycinoyl (CDG) and di-O-piperoyl (CDP) esters of curcumin were found to be comparable with that of curcumin. Both conjugates induced chromatin condensation fragmentation and apoptotic body formation. CDP exposure to MCF-7 cells induced apoptosis initiating loss of mitochondrial membrane potential (${\Delta}{\Psi}m$) followed by inhibition of translocation of transcription factor NF-${\kappa}B$ and release of Cytochrome-C. Reactive oxygen species (ROS) production was evaluated by fluorescent activated cell sorter. Change in ratio of Bcl2/Bclxl was observed, suggesting permeablization of mitochondrial membrane leading to the release of AIF, Smac and other apoptogenic molecules. DNA fragmentation as a hallmark for apoptosis was monitored by TUNEL as well as agrose gel electrophoresis. Thus, it was proven that conjugation does not affect the therapeutic potential of parent molecule in vitro, while these could work in vivo as prodrugs with enhanced pharmacokinetic profile. Pharmacokinetics of these molecules under in vivo conditions is a further scope of this study.

• Journal of the Korea Academia-Industrial cooperation Society
• /
• v.18 no.1
• /
• pp.216-221
• /
• 2017

Reducing optical reflection in the visible light range, in order to increase the share of transmitted light and avoid the formation of ghost images in imaging, is important for polymer lens applications. In this study, polymer lenses with refractive indices of n=1.56, 1.60, and 1.67 were fabricated by the injection-molding method with a polymer lens monomer, dibutyltin dichloride as the catalyst and an alkyl phosphoric ester as the release agent. To investigate their anti-reflection (AR) effects, various AR coating structures, viz. a multi-layer AR coating structure, tri-layer AR coating structure with a discrete approximation Gaussian gradient-index profile, and tri-layer AR coating structure with a quarter-wavelength approximation, were designed and coated on the polymer lens by an E-beam evaporation system. The optical properties of the polymer lenses were characterized by UV-visible spectrometry. The material properties of the thin films, refractive index and surface roughness, were analyzed by ellipsometry and AFM, respectively. The most effective AR coating structure of the polymer lens with low refractive index, n=1.56, was the both side coating of multi-layer AR coating structure. However, both side coating of the tri-layered discrete approximation Gaussian gradient-index profile AR coating structure gave comparable results to the both side coating of the multi-layer AR coating structure for the polymer lens with a high refractive index of n=1.67.