An important factor influencing the rate of absorption of an active agent administered as a tablet or other solid dosage formulation, and thus the efficacy and safety of the formulation, is the rate of dissolution of the dosage form in the body fluids of a human or animal
The ability of components of the formulation to influence the rate of release of the active agent(s) thus constitutes the basis for the so-called controlled-release, extended-release, sustained-release or prolonged-action pharmaceutical preparations that are designed to produce slow, uniform release and absorption of the active agent over a period of hours, days, weeks, or months. Advantages of controlled-release formulations include a reduction in the required frequency of administration of the drug as compared to immediate-release dosage forms, often resulting in improved patient compliance; maintenance of a relatively stable concentration of the drug in the body leading to a sustained therapeutic effect over a set period of time; and decreased incidence and intensity of undesired side effects of the active agent resulting from a reduction of the high plasma concentrations that often occur after administration of immediate-release dosage forms
Many materials have been proposed and developed as matrices for controlled release of active agents, i.e. drugs, pro-drugs, etc. These include polymeric materials such as polyvinyl chloride, polyethylene amides, ethyl cellulose, silicone and poly (hydroxymethyl methacrylate). See, for example, U.S. Pat. No. 3,087,860 to Endicott et al.; U.S. Pat. No. 2,987,445 to Levesque et al.; Salomon et al., Pharm. Acta Helv., 55, 174-182 (1980); Korsmeyer, Diffusion Controlled Systems: Hydrogels, Chap. 2, pp 15-37 in Polymers for Controlled Drug Delivery, Ed Tarcha, CRC Press, Boca Raton, Fla. USA (1991); and Buri et al., Pharm. Acta Helv. 55, 189-197(1980).
High amylose starch has also been used for controlled-release purposes, and, in particular, recent advances have been made using cross-linked high amylose starch. For example, U.S. Pat. No. 5,456,921 (Mateescu et al.), which issued Oct. 10, 1995, U.S. Pat. No. 5,616,343 (Cartilier et al.), which issued Apr. 1, 1997, U.S. Pat. No. 6,284,273 (Lenaerts et al.), which issued Sep. 4, 2001, U.S. Pat. No. 6,419,957 (Lenaerts et al.), which issued Jul. 16, 2002, and U.S. Pat. No. 6,607,748 (Lenaerts et al.), which issued Aug. 19, 2003, describe solid controlled release oral pharmaceutical dosage units in the form of tablets comprising a dry powder of a pharmaceutical product and a dry powder of cross-linked high amylose starch in which the cross-linked high amylose starch includes a mixture of about 10-60% by weight of amylopectin and about 40-90% amylose.
Further examples of controlled-release materials include Kollidon™ SR marketed by BASF (Germany), this material being a physical mixture of polyvinyl acetate (PVA) and polyvinylpyrrolidone (povidone), reportedly made up of about 80% PVA and 19% povidone, and approximately 0.8% sodium dodecylsulfate and about 0.2% silica as stabilizer. BASF Technical Information (July 2001) discloses that Kollidon™ SR can be used in the preparation of sustained release matrix dosage forms including tablets, pellets and granules, and that different technologies such as direct compression, roller compaction, wet granulation and extrusion may be employed in the manufacture of pharmaceutical formulations. A number of patent publications provide further information on PVA-povidone mixtures: U.S. Patent Publication No. 2001/0038852 (Kolter et al.) published Nov. 8, 2001; U.S. Patent Publication No. 2002/0012701 (Kolter et al.) published Jan. 31, 2002, and U.S. Patent Publication No. 2003/0021846 (Kolter et al.) published Jan. 30, 2003.
Extended and controlled release formulations relating to tramadol have been suggested, examples being described in: U.S. Patent Publication No. 2003/0143270, (Deboeck et al.) published Jul. 31, 2003; U.S. Pat. No. 6,254,887 (Miller et al.) issued Jul. 3, 2001; U.S. Patent Publication No. 2001/0036477 (Miller et al.) published Nov. 1, 2001; U.S. Pat. No. 6,326,027 (Miller et al.) issued Dec. 4, 2001, WO 03/080031 (CILAG AG et al.) published Oct. 2, 2003. Articles have been published in which comparative data between “once-daily” tramadol formulations and immediate release tramadol formulations are presented: Adler et al., “A Comparison of Once-Daily Tramadol with Normal Release Tramadol in the Treatment of Pain in Osteoarthritis,” The Journal of Rheumatology (2002) 29(10): 2195-2199; and Bodalia et al., “A Comparison of the Pharmacokinetics, Clinical Efficacy, and Tolerability of Once-Daily Tramadol Tablets with Normal Release Tramadol Capsules,” Journal of Pain and Symptom Management (2003) 25(2): 142-149.
Citation or identification of any reference in this specification is not intended to be construed as an admission that such reference is available as prior art to the present invention.