Creative Innovation For Better Healthy Life

GLARS

GLARS(Geometrically Long Absorption Regulated System)

Shortcomings of Conventional Sustained Release Drug Delivery Systems

Conventional sustained release drug delivery systems such as ALZA’s OROS (Osmotic Release Oral System) and Skyepharma’s Geomatrix, have enjoyed great success in the field of drug dosage form reformulation; they have enabled many famous products like Doxazosin, Nifedipine, Oxybutynine, Paroxetine and Alfuzosin to be administered less frequently.
Although these systems extend the drug release up to 24 or 48 hours, the simple extension of drug release time would be meaningless because a practical absorption site of overall drugs is limited to a small intestine - consider the total transit time along the small intestine with absorption will be only 4 to 6 hrs. This means that relatively large amounts of the incorporated drug would pass out without a sufficient practical absorption.

New Solution to Sustained Absorption by Extending the Absorption Site

To overcome the shortcomings of the currently existing sustained release drug delivery technologies we have recently developed a novel drug delivery system to enable a drug to be dissolved irrespective of the surrounding environment and further absorbed up to colon. We coined this “Geometrically Long Absorption Regulated System(GLARS)”.
Basically, this system is a triple-layered tablet, comprised of upper and lower layers that swell and draw a sufficient amount of water, plus a highly water - soluble middle layer that rapidly draw water into the tablet core simultaneously.

The water drawn into the tablet (about 3 to 4 times the weight of the tablet itself) functions as an additional media which enables additional and later drug release out of the dosage form. This serves to overcome the shortage of surrounding media that has been reported to be one of the key reasons for mal-absorption of a drug in colon.

As the middle layer induces a rapid water draw into the tablet core, the penetrated water also diffuses to the upper and lower layers, which makes the tablet to rapidly swell and controls drug release.

At virtually the same time, the swollen upper and lower layers form to surround a lateral side of the middle layer, which can, in turn, further control drug release.

This relatively rigid swollen matrix structure makes drug release not affected by surrounding mechanical flux, which can provide relatively consistent in vivo drug release irrespective of degree of gastrointestinal motility.

Several in vivo evidences have been established;

Scintigraphic movie of the GLARS tablet in the GI transit

Scintigraphic images of the GLARS tablet in the GI transit

Tamsulosin HCl (Astellas / Boehringer-Ingelheim ; Harnal®D or Flomax® ; Anti-BPH ; Currently re-formulated in Europe as Alna OCAS®, Flomaxtra®, etc. ; Human)

PK parameters Harnal®D 0.2mg Omix® OCAS 0.4mg GL2702 0.4mg
Mean SD n Mean SD n Mean SD n
Cmax,ss(ng/mL) 9.98 3.50 24 16.57 11.77 24 17.02 9.04 24
AUCall(hr*ng/mL) 164.53 82.94 24 353.70 324.11 24 314.85 171.30 24

Remarkable duration of plasma concentration of our system without the increase of peak concentration is important in that higher peak concentration of Tamsulosin could give rise to the known adverse effect like orthostatic hypotension.

Products by GLARS
Pipeline Brand Usage Status Remark
1   Tamsulosin GLARS Alna® OCAS® BPH Phase III  
2   Pregabalin GLARS Lyrica® Pain Phase I