Sustained release matrix systems for highly soluble drugs

Abstract

Disclosed are sustained release oral solid dosage forms comprising a therapeutically effective amount of a medicament having a solubility of more than about 10 g / l; a pH modifying agent; and a sustained release matrix comprising a gelling agent, said gelling agent comprising a heteropolysaccharide gum and a homopolysaccharide gum capable of cross-linking said heteropolysaccharide gum when exposed to an environmental fluid, said dosage form providing a sustained release of said medicament after oral administration to human patients.

Description

[0001] This application claims the benefit of provisional application Serial No. 60 / 157,200 filed Sep. 30, 1999, the disclosure of which is hereby incorporated by reference.[0002] The advantages of controlled release products are well known in the pharmaceutical field and include the ability to maintain a desired blood level of a medicament over a comparatively longer period of time while increasing patient compliance by reducing the number of administrations necessary to achieve the same. These advantages have been attained by a wide variety of methods. For example, different hydrogels have been described for use in controlled release medicines, some of which are synthetic, but most of which are semi-synthetic or of natural origin. A few contain both synthetic and non-synthetic material. However, some of the systems require special process and production equipment, and in addition some of these systems are susceptible to variable drug release.[0003] Oral controlled release delivery...

AI Technical Summary

Benefits of technology

[0028] It is a further object of the present invention to provide a formulation which can provide multi-phasic or bi-phasic controlled release for soluble to highly soluble medicaments.

[0117] Based on the dosage of diltiazem in the sustained release oral formulations of the invention, one can easily determine the Cmax #1, Cmax #2, Tmax #1 and Tmax #2 for different dosages of diltiazem over a 12 or 24 hour period.

Problems solved by technology

However, some of the systems require special process and production equipment, and in addition some of these systems are susceptible to variable drug release.

Moreover, other factors may influence the reaction rate, including temperature, pH, food effect variability, ions and ionic strength dependency, viscosity dependency, corrosion / erosion variability, content uniformity problems, flow and weight uniformity problems, carrying capacity and mechanical strength problems, hydrolysis, photochemical decomposition, interaction between components (such as interactions between the drug and other ingredients in the formulation, such as buffers, preservatives, and the like), the concentration of solvents of low dielectric constant (when the reaction involves oppositely charged ions), etc.

While many controlled and sustained release formulations are already known, certain soluble to highly soluble drugs present formulation difficulties when included in such formulations.

Sustained release formulations with soluble drugs are susceptible to "dose dumping".

This elevated release rate is associated with blood plasma fluctuations which can possibly result in decreased therapeutic effect or increased toxicity.

These are the same problems which sustained release formulations are supposed to solve.

Further, it is often not possible to readily predict whether a particular sustained release formulation will provide the desired sustained release for a soluble to highly soluble drug.

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