The first patent within the technology, referred to as the Dual Polymer platform, was developed specifically for the controlled release of highly soluble actives, and involves the granulation of an active pharmaceutical ingredient (API) with one or more polymers or gums of differing swelling characteristics. The differential hydration rates of each polymer may be combined to suppress the diffusion of the imbedded drug for up to 24 hours. This method of controlled release results from the reversible complexation of the API and the polyionic matrix, initiated during in-situ hydration.

APIs with poor flow properties may be combined with better flowing controlling polymers and excipients during the granulation step to yield a more manufacturable tablet. APIs with poor compression characteristics or those formulations that require a large drug load to be therapeutically effective may also be combined with more compressible materials and high-viscosity polymers to allow for the manufacture of a lower-volume dosage form than is possible with other matrix technologies, such as Penwest's TIMERx® system1.

The second patent - referred to as the Electrolyte platform - employs the colloidal chemistry phenomenon of "salting-out" to moderate the swelling and erosion kinetics of a non-ionic polymer matrix containing the API and one or more electrolytes. The presence of these electrolytic compounds in the form of ionizable salts allows for non-collapsible diffusion channels to form; c hannelization agents used in the past were not ionizable, therefore, the diffusion channels were unpredictable leading to poor release profiles and lack of control. The electrolytes also contribute to a contracting micro-environment within the tablet, whose pH is mediated by the pKa of the electrolyte, thus either enhancing or suppressing the solubility of the API itself. As the matrix hydrates, the electrolytes and polymer compete for water of hydration with the API, resulting in a programmable rate of release.

The result is a system which is capable of zero-order, pH-independent release of an API for up to 24-hours, without regard to the solubility of the API itself. Because the system consists of a non-covalently bonded matrix, the manufacturing process is a fundamentally two-step process of simple dry-blending and direct compression. This two-step process allows for the manufacture of a monolithic tablet with cost advantages comparable to a simple wax-matrix, yet provides release profiles comparable to an osmotic pump or multi-layer tablet.

Amino Acid Platform
(US Patent #6,517,868 - Issued February 11, 2003)
(US Patent #6,936,275 - Issued August 30, 2005)
(US Patent #7,229,642 - Issued June 12, 2007)

The third, fourth, and fifth most recent patents - referred to as the Amino Acid platform - have applied theories of colloidal chemistry in the formulation of a matrix comprised of an API granulated with one or more ionic resins or polysaccharide gums and one or more amino acids, within a second dry-blended matrix similar composition. The ionic interaction between the granulated and dry-blended constituents allows for the controlled release of an API over 24-hours, independent of its solubility.

Polysaccharide gums have demonstrated the ability to formulate for high drug load, prolonged delivery, resulting in a reduction in dosing frequency and minimization of additional compression-aiding excipients required for successful, high-throughput tableting. The ionic resins and charged amino acids allow for a contracting micro-environment similar to that observed in the Electrolyte platform.

* compound-dependent

In the delivery of non-BCS Class I compounds, (i.e. those compounds with low solubility or permeability), it is often advantageous to alter the physiochemical characteristics of the drug through improvements in solubility or permeability. Many delivery technologies employ techniques such as the selection of a more soluble salt or reduced particle size of the active, or use surfactants or self-emulsifying processes to improve solubility; permeability enhancers such as co-solvents, lipid-filled capsules and liposomes may also be employed. The incorporation of such techniques into controlled release delivery systems presents many obstacles however, since increasing the solubility of the active creates the need for more effective controlling methods - greater gel viscosity, controlling polymer volume, reduction in hydration rate - and may even be incompatible with the mechanism of control itself or impart undue complexity unto the process of manufacture. SCOLR's Amino Acid platform employs the colloidal chemistry technique of "salting in," that preliminary data indicates may improve the solubility of BCS Class III compounds without compromising the controlled release characteristics of the delivery system.

Biopharmaceutical Classification Scheme (BCS)

(R. Fassihi, 2002)

TIMERx® is a registered trademark of Penwest, Inc.