Hyunjo Kim

A New Ternary Polymeric Matrix System for Controlled Drug Delivery of Highly Soluble Drugs: I. Diltiazem Hydrochloride

AbstractPurpose. The purpose of this study was to develop a new ternary polymeric matrix system that is easy to manufacture and that delivers a highly soluble drug over long periods of time. Methods. Pectin, hydroxypropylmethylcellulose (HPMC), and diltiazem HC1 granulated with gelatin at optimized ratios were blended at different loading doses and directly compressed. Swelling behavior, dissolution profiles and the effect of hydrodynamic stress on release kinetics were evaluated. Results. Diltiazem release kinetics from the ternary polymeric system was dependent on the different swelling behavior of the polymers and varied with the drug loading dose and hydrodynamic conditions. Drug release followed either non-Fickian or Case II transport kinetics. The relative influence of diffusion and relaxational/dissolution effects on release profiles for different drug loadings was calculated by a nonlinear regression approach. Photographs taken during swelling show that the anisotropic nature of the gel structure, drug loading dose, swelling capacity of polymers used, and the design of delivery system all play important roles in controlling the drug release and dissolution/ erosion processes. Conclusions. Zero-order delivery of diltiazem HC1 from a simple tablet matrix was achieved. The ternary polymeric system developed in this study is suitable for controlled release of highly soluble drugs. It offers a number of advantages over existing systems, including ease of manufacturing and of release modulation, as well as reproducibility of release profiles under well defined hydrodynamic conditions. Our delivery system has the potential to fully release its drug content in a controlled manner over a long time period and to dissolve completely.

Compactibility characterization of granular pectin for tableting operation using a compaction simulator

Abstract Pectin has great potential as a tableting excipient and drug carrier to the colon. It is a non-toxic, soluble polysaccharide which passes through the stomach and small intestine with limited digestion, but is totally metabolized by the colonic microflora. In the past, drug–pectin matrices coated with pH-dependent polymers have been investigated for possible drug delivery to the colon. Although many scientists have used pectin, its feasibility in terms of tablet manufacturability with a high-speed machine has never been evaluated. In this report compactibility of different pectin types (low and high methoxylated) for large-scale tableting operation have been evaluated. The compactibility behavior of granular pectins were studied by a compaction simulator. It was found that pectin on its own does not produce tablets of acceptable quality even at a punch velocity as low as 20 rpm (e.g. low tensile strengths, capping and lamination irrespective of applied compression force). Heckel plots were constructed and changes in porosity at different compaction pressures and punch velocities were determined. Yield pressures for the pectin at a maximum punch velocity of 50 and 250 mm/s were 200 and 213 MPa, respectively. Such close values indicate that this material primarily consolidates by fragmentation with little plastic deformation. This was further evidenced from a low strain rate sensitivity value (SRS=6.1%) for high methoxylated pectin. The high apparent porosity of 13.8% at 160 MPa shows significant resistance to densification, and compacts underwent substantial elastic recovery (18–25%) during decompression and ejection. These findings suggest that pectin is hard, rigid and poorly compactible. To improve tabletability of pectin, a 50/50 binary mixture with microcrystalline cellulose was evaluated and excellent compacts were produced at all compaction rates and pressures. It is concluded that frequent structural failures observed in both pectin types are due to lack of plastic deformation, poor compactibility and high elastic recovery.

A Novel Drug Delivery System Design for Meloxicam

A drug delivery system(DDS) for practically insoluble meloxicam was developed and evaluated by dissolution study. A novel DDS is two layered system, where the first layer is consisted of gas-forming agent for an immediate release and the second layer is composed of metolose SR(HPMC) for sustained release. This bilayered tablets were manufactured by using manual single punch machine. The results of dissolution study showed an initial burst release followed by sustained release for the experimental period time. From a pharmaceutical point of view, the designed DDS for meloxicam would be informative system in terms of poorly soluble analgesic medicines.

Compaction Simulator Study on Pectin Introducing Dwell Time

Although many scientists have used pectin, its feasibility in terms of tablet manufacturability with a high speed machine has never been evaluated. Therefore, compactibility of different pectin types for large scale tableting operation has been evaluated. The compactibility behavior of powder pectins was studied by a compaction simulator. It was found that pectin on its own does not produce tablets of acceptable quality even at a punch velocity as low as 20 rpm (e.g. low tensile strengths, capping and lamination irrespective of applied compression force). Thus, dwell time was introduced and more hard compact was produced as relaxation time in die increases. It was concluded that frequent structural failure observed in both pectin types was due to lack of plastic deformation, poor compactibility and high elastic recovery.

A Novel Drug Delivery Approach to Olanzapine Orally Dispersible Tablet (ODT) in the Phase of Schizophrenia and Its Pharmacokinetics

The present work focuses on preparation of olanzapine, orally dispersing tablets by direct compression method. Effect of super disintegrant crospovidone, disintegration time, drug content on in vitro release has been studied. A factorial design was employed in formulating a prompt dispersible tablet. The selected independent variables crospovidone and fmelt showed significant effect on dependent variables i.e. disintegration time and percent drug dissolved. Disintegration time and percent drug dissolved decreased with increase in the level of crospovidone. The similarity factor f2 was found to be 97.48 for the developed formulation indicating the release was similar to that of the marketed formulation. Phar- macokinetics of olanzapine after single-dose oral administration of orally disintegrating tablet in normal volunteers were evaluated and the results showed that PK parameters (Cmax, Tmax, AUC) of the designed ODT matrix were similar to those of commercial product, Zyprexa Zydis ® as a reference.