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CDT® Technology Comparison |
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The opportunities for increased patient compliance, patent extension, product differentiation, and heightened safety and efficacy offered by CR technologies have resulted in the development of multiple delivery platforms to address the wide range of APIs and their physiochemical characteristics such as solubility, compressibility and flowability. While all of the delivery technologies discussed herein may be classified as "timed release" because they mitigate spikes in serum levels of the drug being released to a greater degree than IR dosage forms, their effectiveness in controlling drug release varies widely. Each broad category of delivery technology - diffusion, reservoir, coated-bead and multi-particulate, pore-forming wax, and geometric-physical devices - has traditionally been limited in the specific types of pharmacokinetic release profiles that may be obtained. Few delivery technologies are capable of 24-hour near-linear release; this is often as dependent upon the physical characteristics of the delivery system as upon the characteristics of the API itself. Diffusion tablet systems rely on hydrophilic polymer swelling for control of drug release, and may then be coated with diffusion barriers to further control drug release. These systems often employ granulation steps to incorporate the drug in a single polymer such as polyethylene oxide or hydroxypropyl methylcellulose; the diffusion barriers are often formed from film-forming polymers such as acrylic resins or ethyl cellulose. These granulation and coating processes add extra processing steps, variability and cost to manufacturing. While such have yielded acceptable sustained release patterns for short durations, it is difficult to produce a linear release over 12 to 24 hours.
SCOLR Pharma's self-correcting systems offer an advantage over single polymer diffusion systems by employing additional materials that work with the physical properties of the API and polymer to further control tablet hydration and the release of the drug. These systems have produced linear release profiles over durations up to 24 hours without the need for multiple layers within the tablet. Reservoir devices usually consist of a semi-permeable barrier that is involved in the release of the API from a core site within the tablet. The manufacturing process may involve incorporating laser-bored orifices in the semi-permeable membrane. Although capable of producing a linear release pattern, factors such as the complexity of design, necessary manufacturing processes, and specialized equipment, may result in producing an unbalanced cost-benefit ratio.
SCOLR Pharma's monolithic matrix systems eliminate the need for costly manufacturing processes such as creating coating membranes with precise release orifices; in the case of the Electrolyte platform, a simple two step process of dry blending and direct compression is all that is necessary. A matrix system is less susceptible to tablet damage that may alter release rate of the drug than a semi-permeable membrane system; a coated reservoir system may develop leaks if the membrane is compromised after manufacture. Further, osmotic systems are often limited to low doses of drugs due to size limitations of the tablet. SCOLR Pharma's electrolyte patent has proven to be effective for high doses of drugs; in some cases with little controlling excipient necessary so the overall tablet size is minimized. Coated-bead and multi-particulate systems often employ pH-sensitive, enteric, or sustained release coatings upon aggregate or non-pareil granules of the API. These granules may then be packaged in a capsule or compressed with additional excipients to form a tablet. The API may also be blended or granulated with polymers before coating to provide an additional level of control; these systems may also appear as a blend of coated-beads with differing release rates for extended release or pulsitile release formulations. Regardless of the manner of manufacture, coated bead systems are extremely complex to produce, requiring large numbers of excipients, use of solvents and multiple manufacturing steps.
SCOLR Pharma's monolithic systems employ the tablet matrix itself as the rate-controlling mechanism instead of complex coating processes, and because the drug is incorporated into the matrix itself, there is no need for a non-pareil template to shape or build upon. SCOLR Pharma's matrix technologies are as flexible as multi-particulate systems, allowing formulations as both capsule and tablet dosage forms with fewer manufacturing steps. Pore-forming wax systems incorporate the API into a wax base via tableting and rely upon the rate of erosion to control the release of the drug. The API and a water soluble excipient (such as a polymer or salt) are introduced into a wax or wax-like compound (such as paraffin) and then placed in an aqueous environment in order to allow the water soluble polymer to dissolve out of the wax, resulting in the formation of pores. Upon contact with the gastrointestinal fluid, the pores facilitate erosion of the wax and the subsequent release of the active ingredient. This erosion is often non-linear - the accuracy and efficacy of the resulting rate of release is often of insufficient precision for many pharmaceutical products - and is rarely capable of controlling drug release a near-linear fashion over 24 hours, because the high volume of controlling excipient required for such a duration often results in a significant portion of the drug remaining trapped in the wax matrix.
SCOLR Pharma's monolithic systems employ both diffusion and erosion to mediate drug release from the tablet, thus exhibiting far more reproducible release than non-linear erosion systems. The self-correcting nature of the ionic gel matrices controls both polymer hydration and erosion, this allows for near-linear release throughout 24 hours as gel formation progresses toward the dry central core and erosion continues at the outer boundary of the gel layer. The use of channelization agents within the gel layer ensures the complete hydration of the matrix and corresponding complete release of the drug from the dosage form. Geometrical-physical systems incorporate the active ingredient into a layer or core, which is then formed into a pellet and altered by physical means to effect and control the rate or erosion or dissolution of the dosage form. Surface-area modifications are often employed to retard the burst release of highly soluble actives or increase the extent of the release of actives from tablet cores that possess diffusion limitations. The physically-altered pellet may then be incorporated alone or in combination with other modified pellets and excipients into a capsule or tablet. These systems can be quite simple, such as an enteric-coated tablet, or highly complex, such as the modified-core tablet systems of Procise®, developed by GlaxoSmithKline1, and Smartrix®, developed by Smartrix Technologies2. Many of the physical-geometric delivery system designs are intentionally complex so as to remain distinctive and proprietary while also providing a significant degree of flexibility in formulation and a wide range of available release profiles. Because the rate and extent of release is dependent upon the how the physical alteration to the tablet is affected in vivo, variations in the coatings or barriers dramatically affect the release of the active ingredient, may result in a high degree of in vivo release variability.
SCOLR Pharma's monolithic matrix systems allow for highly reproducible release in vivo because of a reliance upon the uniform hydration of the entire dosage form rather than a select portion of the tablet, as is often the case with physical-geometric systems. The lack of intricate physical manipulation during production minimizes the cost of manufacture, but because of the full patent life of all SCOLR Pharma platforms, such manufacturing efficiency does not sacrifice the proprietary nature of the technology. Procise® is a trademark of GlaxoSmithKline. CDT® Technology Comparison Summary Table
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